EYE DROP DISPENSER

CROSS REFERENCE

[0001] This application claims the benefit of priority from U.S. Provisional Application No. 62/900,092, filed September 13, 2019. The foregoing related application, in its entirety, is incorporated herein by reference.

[0002] In addition, each of the references identified herein, in their entirety, are incorporated herein by reference.

FIELD OF THE INVENTION

[0003] This relates to eye drop dispensers, comprising a container part (eye drop bottle), a dropper part (eye drop nozzle), and a cap (lid) part, and methods of delivering ophthalmic compositions while using the same.

BACKGROUND OF THE INVENTION

[0004] Ocular medications are traditionally instilled as a drop in the lower conjunctival sac, and this remains the preferred dosage form for topical ocular medications (1). An immediate issue is that while the maximum capacity of the conjunctival sac is ~20pL (2) (and the volume of the tear film is 7pL (3)), it has been determined that the average eye drop size of many commercially available topical medications is 39pL (range of 25.1 to 56.4 pL (4), contributing to medication wastage and increased treatment cost (5). Furthermore, the larger the volume instilled, the more rapid the drainage via the naso-lacrimal duct, increasing systemic drug absorption in the duct, nasopharynx, bypassing hepatic first-pass metabolism (see 1). Gastrointestinal drug absorption can also occur, potentially contributing to systemic side effects (see 1).

[0005] The introduction of semifluorinated alkanes (having a perfluorocarbon and a hydrocarbon segment in the molecule), physically, chemically and physiologically inert, colorless liquids with substantially reduced densities and very low surface and interface tensions (10) in the management of dry eye syndrome (11,12) has been an important advance. Wetting agents for the ocular surface with minimal associated blur, they do not need to be combined with a preservatives, since as a their completely nonaqueous nature precludes microbial growth. They demonstrate significant spreading ability, reduce shearing forces between surfaces - the globe of the eye and the eyelids. Use of these substances in ophthalmology is likely to increase as they are being developed as drug delivery systems (13,14).

[0006] However, these beneficial characteristics of semifluorinated alkanes (SFA) in relation to the ocular surface have created problems in relation to eye drop delivery. The current packaging of these eye drops is such that, despite relatively small eye drop size (~1 lpL), a relatively light squeeze of the bottle results in rapid eye drop efflux and considerable wastage and consequent expense. The very specific, 12-step instructions in the packaging instruct the patient in how to create vacuum in the bottle by holding it nozzle upwards, pressing the bottle between index finger and thumb (to express air from the bottle) then keeping the bottle under slight pressure, everting the bottle so that the nozzle now points downwards, reducing the finger pressure on the bottle (to allow some air to flow back into the bottle), positioning the bottle over the eye and applying gentle pressure to then expel one drop. The properties of these drops are such that when they do not create a strong sensation when they hit the ocular surface, so eye drop application in front of a mirror is recommended. These maneuvers exceed the manual dexterity of many, mostly elderly patients (in whom dry eye prevalence is high) and they revert to standard inverted method of eye drop application, resulting in excessive flow and wastage.

[0007] The eye drop dispenser (1) provided herein, including the container (2) and bottle (5), the nozzle (3), the base support (4), and methods of using and processes of filing the same, address one or more of the above noted problems.

BRIEF SUMMARY OF THE INVENTION

[0008] Eye drop size is determined by many factors, including three major factors: (1) design and characteristics of the dropper tip and bottle, (2) physico-chemical properties of the solution being dispensed including, surface tension, viscosity, density, temperature, and cohesion forces of the solution and the degree of adhesion to the plastic or glass of the drop dispenser orifice (1), and (3) patient’s handling the dropper bottle (increasingly a problem in an ageing population (9).

[0009] In general terms, a decrease in drop size, to between 5pL and 15pL reduces the amount of overflow, the rate of drug loss through drainage, the incidence of systemic side effects, and therapy cost (see (1)).

[0010] For plastic bottles, now the usual means by which water-based eye drops are dispensed, the plastic tips may have a number of configurations, such as the series of nozzle configurations illustrated in Figures 1A-1D. FIG. 1A shows a nozzle with an interior cavity and a small calibrated opening for liquid passage. FIG. IB shows an elongated narrow central duct (an outflow channel) in the tip of the nozzle, wherein the outflow channel is a straight, narrow, cylindrical channel of uniform cross-section. This configuration is designed to prevent a jet when the bottle is squeezed. FIG. 1C shows a nozzle with a rounded tip and a conical outflow channel and an outer orifice (dropper mouth) located on a hemispherical surface. FIG. ID shows a nozzle having an outflow channel consisting of both a conical portion (proximal to the dropper mouth) and a straight cylindrical portion (distal to the dropper mouth). Both the conical and straight cylindrical portions can be of variable lengths. To address these issues, we have designed both a new nozzle to control and restrict flow and wastage as well as a new bottle that aids in the control of eye drop outflow. In particular, the configuration of eye drop dispenser (1) provided herein, including the configuration of the nozzle (3), the bottle (5), the base support (4), and well as the process of filling and sealing the eye drop dispenser (1), will facilitate the methods of topically administrating SFAs, and will facilitate less wastage (if any) and better patient compliance overall.

[0011] Conventional eye drops are usually water-based compositions. When administering such water-based eye drops to the eye, the patient usually inverts the eye drop dispenser that holds the ophthalmic composition and exerts a pressuring force to the flexible bottle in order to force one or more drops to be released from the (eye) dropper bottle. This is usually done by simply squeezing the inverted eyedropper bottle resulting in the release of one or more drops (the aforementioned method is referred to as “pressure method” throughout this document).

[0012] Said conventional administration method (referred to herein as a “pressure method”) known from water-based ophthalmic compositions is not suitable or not reliably suitable for administering ophthalmic compositions comprising SFAs, since SFA-comprising drops may be released from the eyedropper in a rather uncontrolled manner. Without being bound by theory, this is attributed to the interplay of the special surface properties of the amphiphilic SFAs, namely the interplay of high spreading capabilities, high density and/or low surface tension.

[0013] Furthermore, also ocular administration that relies only on the inversion of the eye drop dispenser without exerting a pressuring force to the bottle (the aforementioned method is referred to as "inversion method" throughout this document) is not suitable or not reliably suitable for administering ophthalmic compositions comprising SFAs, since SFA-comprising drops are also released from the eyedropper in a highly uncontrolled manner employing said inversion method. Again, this is attributed to the interplay of the special surface properties of the amphiphilic SFAs, namely the interplay of high spreading capabilities, high density and/or low surface tension.

[0014] Thus, it is an object of the present disclosure to provide an eye drop dispenser that allows for the reliable and controlled administration of liquid compositions, such as ophthalmic compositions, for example, the reliable and controlled topical administration of compositions comprising semifluorinated alkanes (SFAs), to the eye of a patient in a drop-by drop manner. Some embodiments described herein may provide an eye drop dispenser, and processes of fdling and methods of topically administering a liquid composition using the same.

[0015] Furthermore, provided herein is an eye drop dispenser that allows for the reliable, controlled and reproducible administration of liquid compositions, such as topical administration of liquid compositions, comprising semifluorinated alkanes (SFAs) to the eye of a patient in a dropwise manner. Furthermore, the eye drop dispensers disclosed herein allow for the convenient, reliable and reproducible administration of liquid ophthalmic compositions comprising a semifluorinated alkane in therapeutically relevant drop volumes in the range of 8 to 15 pL. In addition, the use of the eye drop dispensers disclosed herein, can reduce to a large extent or even completely avoid the undesired spontaneous formation of drops or droplets , thereby allowing for precise and reliable dosing of the liquid compositions, which is important for therapeutic applications. Furthermore, it allows for the maximum reduction of the amount of liquid composition that is lost or has to be discarded due to spontaneous and uncontrolled release from the drop dispenser.

[0016] In some embodiments, the eye drop dispenser provided herein works reliably below ambient temperature, namely with ophthalmic compositions stored below ambient temperature (e.g., refrigerated compositions), which is usually problematic especially in the case of the dropwise administration of SFA-based compositions. Employing the eye drop dispenser provided herein, said compositions may be directly administered without the need to equilibrate the composition to ambient temperature before use. The eye drop dispenser provided functions as disclosed herein regardless of the volume of the headspace (gaseous volume that fdls the remainder of the interior volume of the eye dropper dispenser, container, or bottle, in addition to the liquid (ophthalmic) composition) in said eye dropper dispenser, container, or bottle. During ongoing use of the drop dispenser by dispensing the composition, the volume of the headspace in the eye drop dispenser is continuously increasing, as the volume of the liquid ophthalmic composition is decreasing. Such increasing headspace volume often hampers reliable administration of ophthalmic compositions utilizing conventional drop dispensers, especially when SFA-based compositions are employed - which, however is not observed when the eye drop dispenser provided herein is employed.

[0017] In one aspect, provided herein is an eye drop dispenser (1), comprising a container (2), a nozzle (3), and a base support (4), wherein: i) the nozzle (3) comprises a nozzle body (12), said nozzle body (12) comprising an outflow channel (13) that connects the interior volume in the container (2) to the environment, said outflow channel (13) comprising: a) a first restricted channel (14); and b) a second restricted channel (16); and ii) the base support (4) comprises: a) a base side (21); and b) a base bottom (20) configured to support the eye drop dispenser (1) in an upright, inverted position, and has a diameter greater than the diameter of the base side (21).

[0018] In another aspect, provided herein is an eye drop dispenser (1), comprising a container (2), a nozzle (3), and a base support (4), wherein: i) the nozzle (3) comprises a nozzle body (12), said nozzle body (12) comprising an outflow channel (13) that connects the interior volume in the container (2) to the environment, said outflow channel (13) comprising: a) a first restricted channel (14); and b) a baffle (27) configured with a second restricted channel (16); and ii) the base support (4) comprises: a) a base side (21); and b) a base bottom (20) configured to support the eye drop dispenser (1) in an upright, inverted position, and has a diameter greater than the diameter of the base side (21).

[0019] In another aspect, provided herein is an eye drop dispenser (1), comprising a container (2), a nozzle (3), and a base support (4), wherein: i) the nozzle (3) comprises a nozzle body (12), said nozzle body (12) comprising an outflow channel (13) that connects the interior volume in the container (2) to the environment, said outflow channel (13) comprising: a) a first restricted channel (14); b) an outflow chamber portion (15); and c) a baffle (27) configured with a second restricted channel (16) in fluid connection with the outflow chamber portion (15) and the environment; and ii) the base support (4) comprises: a) a base side (21); and b) a base bottom (20) configured to support the eye drop dispenser (1) in an upright, inverted position, and has a diameter greater than the diameter of the base side (21).

[0020] In another aspect, provided herein is an eye drop dispenser (1), comprising a container (2), a nozzle (3), and a base support (4), wherein: i) the nozzle (3) comprises a nozzle body (12), said nozzle body (12) comprising an outflow channel (13) that connects the interior volume in the container (2) to the environment, said outflow channel (13) comprising: a) a first restricted channel (14); b) an outflow chamber portion (15); and c) a baffle (27) configured with a second restricted channel (16) in fluid connection with the outflow chamber portion (15) and the environment; and ii) the base support (4) comprises: a) an interior portion comprising a first connector receptacle (18), a nozzle body receptacle (19), and an elevated protrusion (23) capable of physical communication with said nozzle body (12); and b) an exterior portion comprising a base bottom (20) and a base side (21), and a base opening (22) capable of connecting to the neck (6) of said container (2); wherein said base bottom (20) is configured to support the eye drop dispenser (1) in an upright, inverted position, and has a diameter greater than the diameter of the base side (21).

[0021] In another aspect, provided herein is an eye drop dispenser (1), comprising a container (2), a nozzle (3), and a base support (4), wherein: i) the container (2) is in physical and fluid connection with the nozzle (3), and wherein said container (2) is detachably connected to the base support (4), and wherein said container (2) comprises:

A) a bottle (5) having two or more indents (8) on the sides of the bottle (5) and a rounded top end (7) opposite the neck (6) of the bottle (5), said bottle (5) further comprising an interior volume adapted to be partially filled with a liquid phase (9) and a gaseous phase (10) filling the remainder of the interior volume at a pressure above ambient pressure; and

B) a neck (6) connecting the bottle (5) to the nozzle (3); ii) the nozzle (3) comprises a nozzle connector (11) and a nozzle body (12), wherein:

A) the nozzle connector (11) attaches the neck (6) of said container (2) to the nozzle (3); and

B) the nozzle body (12) comprises an outflow channel (13), said outflow channel (13) comprising: a) a first restricted channel (14); b) an outflow chamber portion (15); c) a second restricted channel (16); and d) optionally, a dimple (17); iii) the base support (4) comprises:

A) an interior portion comprising a first connector receptacle (18), a nozzle body receptacle (19), and an elevated protrusion (23) capable of physical communication with said nozzle body (12); and

B) an exterior portion comprising a base bottom (20), a base side (21), and a base opening (22) capable of connecting to the neck (6) of said container (2); wherein said base bottom (20) is configured to support the eye drop dispenser (1) in an upright, inverted position, and has a diameter greater than the diameter of the base side (21).

[0022] In another aspect, provided herein is a process of filling an eye drop dispenser (1) with a liquid composition, wherein the method comprises: i) providing the eye drop dispenser (1) disclosed herein; ii) filling a bottle (5) of a container (2) with the liquid composition, wherein the container (2) comprises the bottle (5), a neck (6), and a rounded top (7) surface that is opposite the neck (6), and wherein the neck (6) is above a rounded top (7) of said bottle (5) during the filling; iii) attaching a nozzle (3) to the neck (6) of the container (2); iv) applying a pressure above ambient pressure to the contents within the bottle (5) of said container (2); v) while maintaining the pressure above ambient pressure, attaching a base support (4) to the neck (6) to seal the liquid composition inside the bottle (5) of said container (2).

[0023] In another aspect, provided herein is a method of topical administration of a liquid composition pressurized above ambient pressure from an eye drop dispenser (1), wherein the method comprises: i) providing the eye drop dispenser (1) disclosed herein; ii) positioning said eye drop dispenser (1) such that the rounded top (7) is positioned above the base support (4); iii) detaching the base support (4) from the neck (6) of said container (2), wherein the detachment decreases the pressure within said container (2) below ambient pressure; iv) grasping and applying pressure at the indents (8) on the sides of said bottle (5), to dispense one drop of the liquid composition at a time from the container (2); v) releasing the grasped pressure at the indents (8) on the sides of said bottle (5) thereby decreasing the pressure within said container (2) below ambient pressure.

[0024] In another aspect, provided herein is a method of topical administration of a liquid composition at a pressure below ambient pressure from an eye drop dispenser (1), wherein the method comprises: i) providing the eye drop dispenser (1) disclosed herein; ii) positioning the eye drop dispenser (1) such that the rounded top (7) is positioned below the base support (4); iii) removing the base support (4) from the container (2) of said eye drop dispenser (1); iv) exerting a force to the sides of the bottle (5) while holding the container (2) in an upright position such that the outflow channel (13) in the nozzle (3) is not in contact with the liquid composition in said bottle (3), thereby reducing the interior volume of said bottle (5) and forcing a portion of the gaseous phase (10) in said bottle (5) out of the container (2) and into the environment; v) inverting the container (2) to an inverted position, while maintaining the exerted force, such that the liquid composition comes in contact with the outflow channel (13); vi) releasing said first force from the bottle (5) of the container (2) at least partly, thereby reducing the pressure inside the bottle (5) below ambient pressure; and vii) exerting a second force to sides of the bottle (5) of the container (2), while still holding the container (2) in the inverted position in which the liquid composition is in contact with the outflow channel (13), thereby raising the pressure inside the interior volume of the bottle (5) above ambient pressure and releasing the liquid composition dropwise from the nozzle (3) of the eye drop dispenser (1).

DETAILED DESCRIPTION OF THE DRAWINGS [0025] FIGURES 1A-1D: illustrates a series of nozzle configurations: FIG. 1A shows a nozzle with a small calibrated opening for liquid passage. FIG. IB shows an elongated narrow central duct (an outflow channel) in the tip of the nozzle to prevent a jet when the bottle is squeezed, where the outflow channel is a straight, narrow, cylindrical channel of uniform cross- section. FIG. 1C shows a nozzle with a conical outflow channel and an outer orifice located on a hemispherical surface. FIG. ID shows a nozzle having an outflow channel consisting of both a conical and a straight cylindrical portion, and both portions can be of variable lengths.

[0026] FIGURES 2A-2B: illustrate two nozzle configurations: a nozzle having a conical outflow channel and a narrower, straight cylindrical portion distal from the mouth of the nozzle (FIG. 2A), and a nozzle having an outflow channel consisting of a conical portion, a narrower, straight cylindrical portion distal from the mouth of the nozzle, and a narrower, straight cylindrical portion proximal to the mouth of the nozzle (FIG. 2B).

[0027] FIGURES 3A-3B: illustrates two container configuration: a container having 70% or more of the middle portion of the bottle sides being cylindrical and 70% or more of the bottle surface opposite the neck of the container being a flat surface (FIG. 3A), and a container having the middle portion of the bottle sides having 2 or more indents, and 70% or more of the bottle surface opposite the neck of the container being a rounded surface (FIG. 3B).

[0028] FIGURES 4A-4C: illustrate an eye dispenser (FIG. 4A), a base support (FIG. 4B), and an eye dispenser (FIG. 4C).

[0029] FIGURES 5A-5D: illustrates a series of steps in filling and creating a vacuum in an eye drop dispenser, with FIG. 5A (step 1) filling the bottle of the container with a liquid composition, FIG. 5B (step 2) attaching the nozzle to container, FIG. 5C (step 3) apply pressure to the container contents in the bottle and attach the base support to the container, and FIG. 5D (step 4) positioning the eye drop dispenser in the upright position such that the eye drop dispenser is supported by the base support.

[0030] FIGURES 6A-6C: illustrates opening an eye drop dispenser, with FIG. 6A illustrating the nozzle of the eye drop dispenser sealed closed with the interior surface of the base support with the liquid composition contained within in the bottle under pressure (a pressurized liquid composition), FIG. 6B (step 1) upon detaching the container from the base support, the nozzle is unsealed and the pressure is released and external air pressure enters the eye drop dispenser, FIG. 6C (step 2) showing an expanded view of the nozzle upon opening in step 1, illustrating the external air pressure entering into the nozzle from the environment.

[0031] FIGURE 7: illustrates a base support.

[0032] FIGURES 8A-8C: illustrate a nozzle without a dimple located at the proximal end of the outflow channel (FIG. 8A), a nozzle with a dimple located at the proximal end of the outflow channel (FIG. 8B), and a nozzle containing a baffle that has a ridge extending from the baffle and into a groove in the inner wall of the nozzle that defines the outflow channel (FIG.

8C).

[0033] FIGURE 9: illustrates a container of an eye dispenser that is attached to a nozzle

DEFINITIONS

[0034] The term “active pharmaceutical ingredient” (also referred to as “API”) as used herein is understood to refer to any type of pharmaceutically active compound or derivative that is useful in the prevention, diagnosis, stabilization, treatment, or management of a condition, disorder or disease.

[0035]

[0036] The term “therapeutically effective amount” as used herein is understood to refer to a dose, concentration or strength which is useful for producing a desired pharmacological effect. [0037] The term “dropwise” as used herein is understood to refer to a liquid phase, more specifically a liquid composition, that is provided in a drop-by-drop fashion, such that one discrete drop, irrespective of its size or volume, is provided or administered at a time and/or that a plurality of drops or droplets, preferably of the liquid composition, is provided in a consecutive manner, one at a time. For example, in some embodiments, dropwise administration of the liquid composition is performed topically, meaning on the surface, e.g. to the skin or other outer boundary of a human or animal body or any part thereof. For example, in some embodiments, the liquid composition is topically administered to the eye surface or an eye tissue.

[0038] The term “liquid composition” as used herein is understood to refer to any water- containing or water-free liquid, solution, emulsion or dispersion. In some embodiments, the liquid composition may be a liquid solution that may be applied to the human or animal body and that may optionally contain one or more active pharmaceutical ingredient (API) as defined above or further compounds like excipients, may optionally contain one or more active pharmaceutical ingredient (API) as defined above or further compounds like excipients, such as organic solvents, lipids, oils, lipophilic vitamins, lubricants, viscosity agents, acids, bases, antioxidants, stabilizers, synergists, coloring agents, thickening agents, and if required in a particular cases, a preservative or a surfactant and mixtures thereof. In some embodiments, the liquid composition may comprise water, dissolved salts, buffer solutions and solvents known to those of skill in the art to be compatible with the above-described ophthalmic administration. [0039] In some embodiments, for example, useful organic solvents may include, but are not limited to, glycerol, propylene glycol, polyethylene glycol, ethanol, acetone, ethyl acetate, isopropyl alcohol, pentylene glycol, liquid paraffin, triglyceride oils and hydrofluorocarbons. [0040] In some embodiments, for example, useful lipids or oily excipients may include, but are not limited to, triglyceride oils (e.g. soybean oil, olive oil, sesame oil, cotton seed oil, castor oil, sweet almond oil), mineral oil (e.g. petrolatum and liquid paraffin), medium chain triglycerides (MCT), oily fatty acids, isopropyl myristate, oily fatty alcohols, esters of sorbitol and fatty acids, oily sucrose esters, oily cholesterol esters, oily wax esters, glycerophospholipids, sphingolipids, or any oily substance which is physiologically tolerated by the eye.

[0041] In some embodiments, for example, useful antioxidants may include, but are not limited to, vitamin E or vitamin E derivatives, ascorbic acid, sulphites, hydrogen sulphites, gallic acid esters, butyl hydroxyanisole (BHA), butyl hydroxytoluene (BHT) or acetylcysteine.

[0042] In some embodiments, for example, the liquid phase (9) or composition to be dispensed by the present eye drop dispenser (1) may comprise one or more excipients, such as an organic cosolvent, such as an oil selected from glyceride oils, liquid waxes, and liquid paraffin or mineral oil, or said liquid composition may comprise an organic solvent exhibiting a high degree of biocompatibility, such as glycerol, propylene glycol, polyethylene glycol or ethanol.

[0043] In some embodiments, for example, the liquid phase (9) or composition may optionally further comprise one or more pharmaceutical active ingredients (APIs), such as for example: prostaglandin analogs (e.g., latanoprost, unoprostone, travoprost, bimatoprost, tafluprost), beta-blockers, (e.g., timolol, brimonidine), carbonic anhydrase inhibitors ( e.g., acetazolamide, dorzolamide, methazolamide, brinzolamide), antihistamines (e.g., olopatadine, levocabastine), corticosteroids (e.g., loteprednol, prednisolone, dexamethasone), fluorquinolone antibiotics (e.g., moxifloxacin, gatifloxacin, ofloxacin, levofloxacin), aminoglycoside antibiotics (e.g., tobramycin), macrolide antibiotics (e.g., azithromycin), broad spectrum antibiotics (chloramphenicol, thiamphenicol, florphenicol, doxycycline), VEGF-inhibitors (e.g., ranibizumab, bevacizumab, aflibercept), macrolide immunsuppressants (e.g., cyclosporine, tacrolimus, sirolimus), NSAIDs (e.g., bromfenac, nepafenac, diclofenac, ketorolac), other anti inflammatory agents, lifitegrast, the interferons, retinoic acid, rho kinase inhibitors (ripasudil, netarsudil), growth factors (epidermal, nerve, hepatocyte, insulin-like), serum and serum-derived products and other agents such as atropine, caffeine (methylxanthine and related agents).

[0044] The liquid composition to be dispensed by the eye drop dispenser of the present invention may also comprise water, dissolved salts, buffer solutions and solvents known to those of skill in the art to be compatible with the above-described ophthalmic administration or may alternatively be a water-free composition. [0045] In some embodiments, the liquid composition is a water-free composition and comprises semifluorinated alkanes. In some embodiments, the liquid composition is a water-free composition and consists of semifluorinated alkanes.

[0046] The term “ophthalmic composition” as used herein is understood to refer to a liquid composition can be topically administered to the eye, to the eye surface or to an eye tissue of a human or an animal.

[0047] The terms “semifluorinated alkane” or “SFA” as used herein are understood to refer to a linear or branched compound composed of at least one perfluorinated segment (F-segment) and at least one non-fluorinated hydrocarbon segment (H-segment). Semi-fluorinated alkanes have been described for various applications, for example commercially for unfolding and reapplying a retina, for long-term tamponade as vitreous humour substitute (H. Meinert et ah, European Journal of Ophthalmology, Vol. 10(3), pp. 189-197, 2000), and as wash-out solutions for residual silicon oil after vitreo-retinal surgery. For example, WO 2011/073134 discloses solutions of cyclosporine in semifluorinated alkanes of the formula CF3(CF2) _n (CH2) _m CH3, optionally in the presence of a co-solvent such as ethanol, wherein the semifluorinated alkane functions as a liquid drug delivery vehicle for cyclosporine for topical treatment of keratoconjunctivitis sicca. For example, WO 2014/041055 describes mixtures of semifluorinated alkanes of the formula CF3(CF2) _n (CH2) _m CH3. These mixtures are described to be ophthalmically applicable as tear film substitutes or for treating patients with dry eye syndrome and/or meibomian gland dysfunction. In some embodiments, for example, the semifluorinated alkane is a linear or branched compound composed of one perfluorinated segment (F-segment) and one non-fluorinated hydrocarbon segment (H-segment). In some embodiments, for example, the semifluorinated alkane is a compound that exists in a liquid state at least at one temperature within the temperature range of 4° to 40°C. In some embodiments, for example, the perfluorinated segment and/or the hydrocarbon segment of the said SFA optionally comprises or consists of a cyclic hydrocarbon segment. In some embodiments, for example, the SFA may comprise within the hydrocarbon segment an unsaturated moiety.

[0048] In some embodiments, the F-segment of a linear or branched SFA comprises between 2-10 or 3-10 carbon atoms. In some embodiments, the H-segment comprises between 3-10 carbon atoms. In some embodiments, the F- and the H-segment comprise, but independently from one another, 2-10 or 3-10 carbon atoms. In some embodiments, each segment independently from another is having carbon atoms selected from the range of 2-10 or 3-10.

[0049] In some embodiments, the F-segment of a linear or branched SFA comprises between 4-10 carbon atoms and/or that the H-segment comprises between 4-10 carbon atoms. In some embodiments, the F- and the H-segment comprise, but independently from one another, 4-10 carbon atoms. In some embodiments, each segment is independently from another having carbon atoms selected from the range of 4-10. [0050] In some embodiments, the linear semifluorinated alkanes may be referred to as FnHm, wherein F means the perfluorinated hydrocarbon segment, H means the non-fluorinated hydrocarbon segment and n, m is the number of carbon atoms of the respective segment. For example, F4HS is used for 1-perfluorobutylpentane. In some embodiments, linear SFAs that may be comprised by the liquid phases or compositions to be dispensed by the drop dispenser according to the present invention are selected from the group consisting of F4H4, F4HS, F4H6, F4H7, F4H8, FSH4, FSHS, FSH6, FSH7, FSH8, F6H2, F6H4, F6H6, F6H7, F6H8, F6H9,

F6H10, F6H12, F8H8, F8H10, F8H12, F10H10. In some embodiments, said linear SFA is selected from the group consisting of F4H4, F4HS, F4H6, FSH4, FSHS, FSH6, FSH7, FSH8, F6H2, F6H4, F6H6, F6H7, F6H8, F6H9, F6H10, F8H8, F8H10, F8H12, F10H10. In some embodiments, the linear SFA is selected from the group consisting of F4H4, F4HS, F4H6, FSH4, FSHS, FSH6, FSH7, FSH8, F6H4, F6H6, F6H7, F6H8, F6H9, F6H10, F8H8, F8H10, F8H12, F10H10. In some embodiments, the linear SFA is selected from the group consisting of F4H4, F4HS, F4H6, FSHS, FSH6, FSH7, FSH8, F6H6, F6H7, F6H8, F6H9, F6H10, F8H8, F8H10, F8H12, F10H10. In some embodiments, the linear SFA is selected from the group consisting of F4HS, F4H6, FSH6, FSH7, F6H6, F6H7, F6H8. In some embodiments, the linear SFA is selected from F4HS and F6H8. In some embodiments, the semifluorinated alkane comprised by the liquid phase (2) or composition to be dispensed by the drop dispenser (1) according to the present invention is F6H8.

[0051] The term “fill volume,” as used herein, is understood to refer to the volume amount of a liquid phase (9) that may be placed into a bottle (5) and still have a sufficient volume of a gaseous phase (10) in said bottle (5) for the eye drop dispenser (1) to function properly. For example, fill volume does not refer to filling a bottle (5) with an amount of a liquid phase (9) to an extent such there is no volume for a gaseous phase (10).

[0052] The terms “proximal,” “proximal end,” “proximal opening,” “distal,” “distal end,” and “distal opening,” as used herein in the context of describing a position within a nozzle, or a position of a feature within a nozzle, such as the outflow channel of said nozzle, of an eye drop dispenser described herein will be understood to be describing a position that is relative to the position at which an eye drop exits the nozzle of the eye drop dispenser and enters into the environment. The terms that include proximal will be understood to be at a position closer to the position at which an eye drop exits the nozzle of the eye drop dispenser and enters into the environment. The terms that include distal will be understood to be at a position situated away from or in a further distance from the position at which an eye drop exits the nozzle of the eye drop dispenser and enters into the environment.

DETAILED DESCRIPTION OF THE INVENTION [0053] The following disclosure provides many different embodiments, or examples, for implementing different features of the provided subject matter. Specific examples of components and arrangements are described below to simplify the present disclosure. These are, of course, merely examples and are not intended to be limiting. In addition, the present disclosure may repeat reference numerals and/or letters in the various examples. This repetition is for the purpose of simplicity and clarity and does not in itself dictate a relationship between the various embodiments and/or configurations discussed.

[0054] The present application provides an eye drop dispenser (1) comprising a combination of a container (2), a nozzle (3), and a base support (4), suitable for topical administration of a liquid composition, for example, an ophthalmic composition, such as an ophthalmic composition comprising semifluorinated alkanes. The present application further provides processes for filling and sealing the eye drop dispenser (1), and methods of topically administering a liquid composition using the eye drop dispenser (1) to treat ocular diseases and conditions, as disclosed herein.

[0055] In some embodiments, the eye drop dispenser (1) provided herein useful as a medical device that may be used as an eye drop delivery system (eye dropper), but which may also be helpful in administering certain compositions in a drop-by-drop manner to other parts of the body that are accessible to topical administration, such as ear, skin, nose, head, finger or other limbs and which may be made of a flexible material, such as, for example polyethylene or polypropylene. In some embodiments, the container (2) of the eye drop dispenser (1) is at least partially made of a flexible polymer, preferably of a flexible thermoplastic polymer.

[0056] In some embodiments, the eye drop dispenser (1) provided herein includes a container (2) and a nozzle (3). The container (2) is the portion of the eye drop dispenser (1) which holds the liquid phase (9) or composition to be administered dropwise in the amount of a single dose, preferably however in an amount of multiple doses or drops, typically in an amount of 0.1 to 15 ml, more typically in an amount of 0.1 to 10 ml, even more typically in an amount of 0.1 to 5 ml, especially when provided as multiple doses. The container (2) holds an interior space or volume which is at least partially filled with the liquid composition (9) to be administered. The container (2) also holds a gaseous phase (10) which fills the remainder of the interior volume which is not filled with the liquid composition (9) at ambient pressure. The gaseous phase (10) may consist of air or a protective gas or a mixture of air and a protective gas or a mixture of different protective gases and evaporated portions or traces of the components of the liquid composition (9). The gaseous phase (10) as well as the liquid composition (9) is held under ambient pressure, which means that it is under the same pressure as the surrounding atmospheric pressure, at least after the container has been opened.

[0057] In some embodiments, the container (2) of the eye drop dispenser (1) provided herein has a bottle (5) and optionally a substantially stationary section. In some embodiments, the bottle (5) has a displaceable section, such as any portion or area of the container (2) that may be displaced out of its original position relative to a fixed portion of the eye drop dispenser (1), e.g. relative to the nozzle (3) of the eye drop dispenser (1) by an external force applied, for example by pressing, pushing, shifting, tilting or bending out of its original position to a displaced position without affecting the physical integrity of the container (2). In some embodiments, the displacement of the bottle (5) of the container (2) induces a deformation, preferably a reversible deformation of the container part, by which the inner volume of the container part is reduced. Optionally, the container (2) may also comprise a stationary or substantially stationary section which is not or substantially not displaced together with the displaceable section when an external force is applied. The stationary section may or may not be present and may be a separate part connected to the bottle (5) or may be a portion of the displaceable section which may not be displaced relative to fixed portion of the eye drop dispenser (1).

[0058] In some embodiments, the container (2) of the eye drop dispenser (1) provided herein has a bottle (5), wherein the bottle (5) has a deformable wall, which may be fabricated in such a way that allows to be deformed by a pressuring force exerted to it. The deformation of the wall part of the bottle (5) effects the interior volume of the container part to be compressed, resulting in the release of the gaseous phase (10) and/or the liquid (ophthalmic) composition (2) from the interior volume to the environment, as well as the intake of a gaseous phase (e.g., air) into the interior volume. The deformable wall of the bottle (5) may be manufactured from at least a partially deformable material, such as from an at least partially deformable plastic material, such as polypropylene or polyethylene. In some embodiments, the deformable wall may be manufactured from an at least partially manually deformable plastic material. In some embodiments, the deformable wall may be manufactured from an at least partially manually deformable plastic material having a thickness in the range of from 0.4 to 1.6 mm, such as with a thickness in the range of from 0.5 to 1.0 mm, for example, with a thickness in the range of from 0.6 to 0.8 mm.

[0059] In some embodiments, the nozzle (3) and the container (2) are manufactured from plastic (polymeric) material, for example, from a thermoplastic polymeric material, such as, for example polypropylene and/or polyethylene.

[0060] In some embodiments, the nozzle (3) is manufactured from polyethylene. It should be understood, however, that the container (2) and the nozzle (3) may be prepared from the same or different polymeric materials as described above. In some embodiments, the nozzle (3) may be manufactured from polyethylene and the container (2) of the eye drop dispenser (1) may be manufactured from polypropylene.

[0061] In some embodiments, the eye drop dispenser (1) provided herein also has a nozzle (3). The "dropper part" is the portion of the eye drop dispenser (1) through which the liquid composition (9) is discharged or physically released in a dropwise, sometime referred to as in a drop-by-drop manner, from the container (2) and subsequently administered. It may be physically connected to or, more specifically, mounted onto to the container (2) and connects the interior volume of the container (2) to the environment through an outflow channel (13) through which the liquid composition (9) to be administered is discharged.

[0062] In some embodiments, the eye drop dispenser (1) provided herein holds the liquid (ophthalmic) composition (9) to be administered in its interior volume. Besides the liquid (ophthalmic) composition (9) the remaining part of the interior volume is filled by a gaseous phase (10). As described above, said gaseous phase (10) may comprise air or another gas, such as an inert gas (e.g., argon, nitrogen) or evaporated portions or traces of the components of the liquid composition (9). It is understood that, as the volume of the liquid composition (9) is decreasing upon repeated use/release of drops, the volume of the gaseous phase (10) is correspondingly increasing.

[0063] In some embodiments, the outflow channel (13) provided herein may be a channel like device or structure that connects the interior volume of the eye drop dispenser (1) to the environment, safeguarding the fluid (or gaseous) communication between interior volume and the environment. In some embodiments, the outflow channel (13) is delimited at its distal end by the distal opening of the first restricted channel (14d) located inside the interior volume of the eye drop dispenser and by the dropper mouth (26) at its proximal end located outside the interior volume of the eye drop bottle (1). The outflow channel (13) has a total length extending from its distal end (14d) to its proximal end opening (16p) or the dropper mouth (26).

[0064] In some embodiments, the outflow channel (13) may have varying inner diameters in the range of 0.09 to 0.19 mm, irregularly shaped channel designs or channel designs of the first restricted channel (14) of the outflow channel (13) that have a substantially conical shape. In some embodiments, the inner diameter of the first restricted channel (14) of the outflow channel (13) increases or decreases linearly from its proximal end (14p) to its distal end (14d). In some embodiments, the inner diameter at the distal end (14d) is in the range of from about 0.16 to 0.19 mm and the inner diameter at the proximal end ( 14p) is in the range of from about 0.09 to 0.15 mm, wherein the inner diameter gradually decreases from the distal end (14d) to the proximal end (14p). In some embodiments, the inner diameter at the proximal end (14p) is in the range of from 0.09 to 0.15 mm.

[0065] In some embodiments, the first restricted channel (14), the second restricted channel (16), and or the outflow channel (13), may be generated by laser drilling. In some embodiments, the first restricted channel (14), the second restricted channel (16), and or the outflow channel (13), may be prepared or generated or manufactured by standard manufacturing methods or techniques such as, for example, conventional drilling, moulding, or injection moulding, for example, together with injection moulding of the nozzle (3) of the present eye drop dispenser (1). [0066] The term "laser drilling" as used herein shall be understood broadly as any kind of drilling process or technique in which a laser or a laser beam is used to generate a hole or a channel like structure suitable as an outflow channel (13) in the eye drop dispenser (1) or, more specifically, in the nozzle (3) of the eye drop dispenser (1) according to the present invention. The laser drilling may be performed by using an UV-laser, an IR-laser or a C02 laser. For example, the laser drilling is performed by using a UV-laser emitting in the range of 150 nm to 400 nm. A preferred UV-laser is one emitting at a wavelength in the range of 300 to 400 nm or in the range of 320 to 360 nm.

[0067] In some embodiments, the nozzle (3) of the eye drop dispenser (1) provided herein may be made of a polymeric material that can be drilled by laser drilling techniques and, for example, may also be used for injection moulding, such as for example polyethylene and/or polypropylene, for example, polyethylene.

[0068] In some embodiments, the eye drop dispenser (1) provided herein offers higher precision and reproducibility of the drop sizes and volumes to be dispensed, independent of the temperature of the eye drop dispenser (1), liquid composition and/or the environment as well as the actual fdling level of the eye drop dispenser (1) or "headspace" above the liquid composition in the eye drop dispenser (1).

[0069] In some embodiments, a kit is provided that includes an eye drop dispenser (1) provided herein at least partially fdled with a liquid phase (9) and a gaseous phase (10), and directions for use of the eye drop dispenser (1).

[0070] In some embodiments, the kit provided herein comprises an eye drop dispenser (1) provided herein. In some embodiments, the kit also comprises directions for the use of the eye drop dispenser (1).

[0071] In some embodiments, the directions or instructions for use comprised by the kit provided herein may be in any form suited to instruct the user how to perform the topical or topical ophthalmic administration of a liquid phase or liquid composition, for example, comprising or even essentially consisting of semifluorinated alkane. It may be in any readable or tangible form, for example, in printed form or in any machine- or computer-readable form, for example, in form of a machine-readable optical label such as, for example, a barcode or a QR- code. In particularly preferred embodiments, the directions for use are provided in form of an instruction leaflet, product or package insert or as an enclosed label. For example, the directions or instructions for use are provided in printed form, for example in form of a printed label, which may be provided together with the eye drop dispenser (1). For example, such a label may be packaged together with the said eye drop dispenser (1).

[0072] In some embodiments, the method as provided herein of employing an underpressure in the eye drop dispenser, not only works for compositions comprising SFAs, but also for conventional water-based ophthalmic compositions. By using the methods disclosed herein involving liquid compositions contained in an eye drop dispenser that is underpressure, (referred to as an "underpressure method" herein) ophthalmic compositions can be administered to the eye in a highly-controlled fashion, which safeguards the reliably and reproducibly administration of a defined dose of said ophthalmic compositions to the eye.

[0073] In some embodiments, the method as provided herein of employing an underpressure, works reliable also below ambient temperature, namely with ophthalmic compositions that were stored below ambient temperature (e.g., refrigerated compositions), which may be problematic when using the pressure method as well as the inversion method, especially in the case of SFA-based compositions. Employing the methods disclosed herein, said compositions may be directly administered without the need to equilibrate the composition to ambient temperature before use. In some embodiments, the (underpressure method) also works regardless of the volume of the headspace (gaseous volume that fills the remainder of the interior volume of the bottle (5) in addition to the liquid (ophthalmic) composition) in the eye drop dispenser (1). During ongoing use of the composition, the volume of the headspace is continuously increasing, as the volume of the liquid ophthalmic composition is decreasing. Such increasing headspace volume hampers reliable administration of ophthalmic compositions utilizing the pressure method or inversion method, especially when SFA-based compositions are employed - which is not the case when the underpressure method disclosed herein is employed.

[0074] In some embodiments, the method of administration provided herein includes a first force exerted to the bottle (5) of the container (2)container (2) of the eye drop dispenser (1) while the eye drop dispenser (1) is held in an upright position. The term "upright position" means that the drop dispenser is oriented such that the outflow channel (13) is not in contact with the liquid composition (9) held in the container (2). This is usually the case when the eye drop dispenser comprising the outflow channel (13) is oriented upwards and the liquid composition (9), by the force of gravity, is held in the lowermost part, i.e. the rounded top (7) of the bottle (5) of the eye drop dispenser (1). In this orientation, the outflow channel only contacts the gaseous phase (10) and not the liquid composition (9). Accordingly, the term "upright position" also encompasses orientations of the drop dispenser which are not completely perpendicular. It also encompasses inclined orientations of the dispenser with an inclination angle of up to 90°, often with an inclination angle of approximately 0° to 45°, more often with an inclination angle of approximately 0° to 30° between the normal axis of the eye drop dispenser (1) and a perpendicular reference line, as long as the liquid composition does not contact the outflow channel (13).

[0075] Preferably, the first force is a pressuring force exerted to the bottle (5) of the container (2), for example a pressuring force applied by the fingers of a user of the drop dispenser to a flexible wall of the bottle (5). Thereby the interior volume of the container (2) of the eye drop dispenser (1) is reduced and the gaseous phase (10) is at least partly or in whole, preferably partly, forced out of the eye drop dispenser (1) into the environment. [0076] In some embodiments, the method of administration provided herein includes inverting the eye drop dispenser (1) to an inverted position in which the liquid composition (9) is in contact with the outflow channel (13). The term "upright, inverted position" as used herein means that the eye drop dispenser (1) is oriented such that the outflow channel (13) is in contact with liquid composition (9) held in the container (2). This is usually the case when the eye dropper dispenser (1) comprising the outflow channel (5) is oriented downwards and the liquid composition (9), by the force of gravity, is held in the lowermost end of the eye drop dispenser when held in this orientation. In this orientation, the outflow channel (13) only contacts the liquid composition (9) and not the gaseous phase (10). Accordingly, the term "inverted position" also encompasses orientations of the eye drop dispenser (1) which are not completely perpendicular. It also encompasses inclined orientations of the dispenser with an inclination angle of up to 90°, often with an inclination angle of approximately 0° to 45°, more often with an inclination angle of approximately 0° to 30° between the normal axis of the eye drop dispenser (1) and a perpendicular reference line, as long as the liquid composition (9) is in contact with the outflow channel (13).

Eye Drop Dispenser

[0077] In some embodiments, the eye drop dispenser (1) provided herein includes a container (2), a nozzle (3), and a base support (4), wherein: i) the nozzle (3) comprises a nozzle body (12), said nozzle body (12) comprising an outflow channel (13) that connects the interior volume in the container (2) to the environment, said outflow channel (13) comprising: a) a first restricted channel (14); and b) a second restricted channel (16); and ii) the base support (4) comprises: a) a base side (21); and b) a base bottom (20) configured to support the eye drop dispenser (1) in an upright, inverted position, and has a diameter greater than the diameter of the base side (21). [0078] In some embodiments, the eye drop dispenser (1) provided herein includes a container (2), a nozzle (3), and a base support (4), wherein: i) the nozzle (3) comprises a nozzle body (12), said nozzle body (12) comprising an outflow channel (13) that connects the interior volume in the container (2) to the environment, said outflow channel (13) comprising: a) a first restricted channel (14); and b) a baffle (27) configured with a second restricted channel (16); and ii) the base support (4) comprises: a) a base side (21); and b) a base bottom (20) configured to support the eye drop dispenser (1) in an upright, inverted position, and has a diameter greater than the diameter of the base side (21).

[0079] In some embodiments, the eye drop dispenser (1) provided herein includes a container (2), a nozzle (3), and a base support (4), wherein: i) the nozzle (3) comprises a nozzle body (12), said nozzle body (12) comprising an outflow channel (13) that connects the interior volume in the container (2) to the environment, said outflow channel (13) comprising: a) a first restricted channel (14); b) an outflow chamber portion (15); and c) a baffle (27) configured with a second restricted channel (16) in fluid connection with the outflow chamber portion (15) and the environment; and ii) the base support (4) comprises: a) a base side (21); and b) a base bottom (20) configured to support the eye drop dispenser (1) in an upright, inverted position, and has a diameter greater than the diameter of the base side (21).

[0080] In some embodiments, the eye drop dispenser (1) provided herein includes a container (2), a nozzle (3), and a base support (4), wherein: i) the nozzle (3) comprises a nozzle body (12), said nozzle body (12) comprising an outflow channel (13) that connects the interior volume in the container (2) to the environment, said outflow channel (13) comprising: a) a first restricted channel (14); b) an outflow chamber portion (15); and c) a baffle (27) configured with a second restricted channel (16) in fluid connection with the outflow chamber portion (15) and the environment; and ii) the base support (4) comprises: a) an interior portion comprising a first connector receptacle (18), a nozzle body receptacle (19), and an elevated protrusion (23) capable of physical communication with nozzle tip portion (28) of said nozzle body (12); and b) an exterior portion comprising a base bottom (20) and a base side (21), and a base opening (22) capable of connecting to the neck (6) of said container (2); wherein said base bottom (20) is configured to support the eye drop dispenser (1) in an upright, inverted position, and has a diameter greater than the diameter of the base side (21).

[0081] In some embodiments, the eye drop dispenser (1) provided herein includes a container (2), a nozzle (3), and a base support (4), wherein: i) the container (2) is in physical and fluid connection with the nozzle (3), and wherein said container (2) is detachably connected to the base support (4), and wherein said container (2) comprises: A) a bottle (5) having two or more indents (8) on the sides of the bottle (5) and a rounded top end (7) opposite the neck (6) of the bottle (5), said bottle (5) further comprising an interior volume adapted to be partially filled with a liquid phase (9) and a gaseous phase (10) filling the remainder of the interior volume at a pressure above ambient pressure; and B) a neck (6) connecting the bottle (5) to the nozzle (3); ii) the nozzle (3) comprises a nozzle connector (11) and a nozzle body (12), wherein: A) the nozzle connector (11) attaches the neck (6) of said container (2) to the nozzle (3); and B) the nozzle body (12) comprises an outflow channel (13), said outflow channel (13) comprising: a) a first restricted channel (14); b) an outflow chamber portion (15); c) a second restricted channel (16); and d) optionally, a dimple (17); iii) the base support (4) comprises: A) an interior portion comprising a first connector receptacle (18), a nozzle body receptacle (19), and an elevated protrusion (23) capable of physical communication with nozzle tip portion (28) of said nozzle body (12); and B) an exterior portion comprising a base bottom (20), a base side (21), and a base opening (22) capable of connecting to the neck (6) of said container (2); wherein said base bottom (20) is configured to support the eye drop dispenser (1) in an upright, inverted position, and has a diameter greater than the diameter of the base side (21).

[0082] In some embodiments, the eye drop dispenser (1) provided herein includes a combination of a container (2), a nozzle (3), and a base support (4), wherein the container (2) includes a bottle (5) of any suitable kind for handheld use which can hold at least a single dose, for example, multiple doses, of a liquid composition, such as an ophthalmic composition, and which may be designed of a single piece or multiple pieces or parts and which may typically be made of a material which is essentially inert against the liquid composition to be administered and which may be flexible, such as, for example polyethylene or polypropylene. In some embodiments, the bottle (5) of the container (2) of the eye drop dispenser (1) is at least partially made of a flexible polymer, for example, a flexible thermoplastic polymer.

Nozzle (Dropper)

[0083] In some embodiments, the container (2) of the eye drop dispenser (1) provided herein includes nozzle (3). The nozzle (3) provided herein is configured to ensure better restriction (or interruption) in the flow of a liquid composition out of the nozzle, such as a liquid composition comprising a SFA. In some embodiments, restricting or interrupting the flow of the liquid composition is achieved by inserting an additional baffle (or filter) in the proximal portion of the nozzle (3), which may also include a restricted channel or a narrowing aperture (smaller) created by the laser process in creating the aperture of the exit hole in the nozzle (3) (e.g., second restricted channel (16)), such as is illustrated in FIG. 2B, relative to FIG. 2A. FIG. 2A illustrates a nozzle having an outflow channel consisting of a conical portion that has an inner diameter increasing in the direction towards the mouth of the dropper, and a narrower, straight cylindrical portion that is distal from the mouth of the nozzle. FIG. 2B illustrates the nozzle of FIG. 2A with an additional narrow, straight cylindrical portion (second restricted channel (16)) that is proximal to the mouth of the nozzle. In some embodiments, the additional narrow, straight cylindrical portion of the outflow channel is a baffle (27) positioned proximal to the dropper mouth (26) and includes the second restricted channel (16). In some embodiments, the additional narrow, straight cylindrical portion of the outflow channel, the second restricted channel (16), is generated by laser drilling of the nozzle (3). In some embodiments, such additional restrictions in the nozzle (3) will produce and/or maintain a drop size of about 8-12pL.

[0084] In some embodiments, the container (2) of the eye drop dispenser (1) provided herein includes the bottle (5), the neck (6), and the nozzle (3). In some embodiments, the nozzle (3) provided herein comprises a nozzle connector (11) and a nozzle body (12), wherein the nozzle connector (11) attaches the neck (6) of the container (2) to the nozzle (3). In some embodiments, the nozzle (3) provided herein is manufactured as a single unit with nozzle body (12) directly attached to the neck (6), exclusive of a nozzle connector (11). In some embodiments, the nozzle connector (11) and the nozzle body (12) are a single unit. In some embodiments, the nozzle connector (11) and the nozzle body (12) are a single unit, and the nozzle connector (12) is configured with threading or a snapping function sufficient to attach the nozzle (3) to the neck (6). In some embodiments, the nozzle connector (11) has an exterior diameter in the range of about 10-15 mm, such as about 12 mm.

[0085] In some embodiments, the nozzle body (12) is cylindrical or conical in shape, or a mixture of cylindrical or conical shapes. In some embodiments, the nozzle body (12) is cylindrical or conical in shape along the portion distal to the dropper mouth (26). In some embodiments, the nozzle body (12) is conical in shape along the portion distal to the dropper mouth (26). In some embodiments, the nozzle body (12) has an exterior diameter in the range of about 5-10 mm. In some embodiments, the nozzle body (12) has a length in the range of about 8- 15 mm, such as about 12 mm or about 10 mm. In some embodiments, the nozzle body (12) is hemispherical in shape along the portion proximal to the dropper mouth (26). In some embodiments, the nozzle body (12) is hemispherical in shape along the nozzle tip portion (28). [0086] In some embodiments, the container (2) of the eye drop dispenser (1) provided herein ncludes the nozzle (3), wherein said nozzle (3) has an outflow channel (13). In some embodiments, the outflow channel (13) connects the interior volume in the container (2) to the environment, such as connects the interior volume in the bottle (5) to the environment. In some embodiments, the outflow channel (13) comprises a first restricted channel (14) distal to the dropper mouth (26) and a second restricted channel (16) proximal to the dropper mouth (26). For example, in some embodiments, the outflow channel (13) comprises: i) a first restricted channel (14) distal to the dropper mouth (26); ii) a second restricted channel (16) proximal to the dropper mouth (26); iii) an outflow chamber portion (15) in fluid communication between the first restricted channel (14) and the second restricted channel (16); and iv) optionally, a dimple (17) in fluid communication between the second restricted channel (16) and the dropper mouth (26). In some embodiments, the outflow channel (13) comprises a first restricted channel (14) distal to the dropper mouth (26) and a baffle (27) proximal to the dropper mouth (26), wherein the baffle (27) is configured with a second restricted channel (16). In some embodiments, the outflow channel (13) comprises: i) a first restricted channel (14) distal to the dropper mouth (26); ii) a baffle (27) proximal to the dropper mouth (26), wherein the baffle (27) is configured with a second restricted channel (16); iii) an outflow chamber portion (15) in fluid communication between the first restricted channel (14) and the second restricted channel (16) of the baffle (27); and iv) optionally, a dimple (17) in fluid communication between the second restricted channel (16) of the baffle (27) and the dropper mouth (26). In some embodiments, the outflow channel (13) comprises the dimple (17). In some embodiments, the dimple (17) is hemispherical in shape. In some embodiments, the dimple (17) has a variable interior diameter ranging from 0.03 mm to 0.19 mm and a length in the range of about 0.1-1 mm. In some embodiments, the outflow channel (13) is cylindrical or conical in shape, or a combination of cylindrical and conical portions. In some embodiments, the outflow channel (13) has an overall length in the range of about 10-20 mm, such as an overall length in the range of about 10-15 mm, for example, an overall length of about 10 mm or about 12 mm. In some embodiments, the outflow channel (13) has a variable inner diameter in the range or 0.03-0.20 mm. In some embodiments, the outflow channel (13) may have different crosssectional shapes, such as circular, elliptic, rectangular or quadratic. In some embodiments, the crosssectional shapes of the outflow channel (13) is a circular channel.

[0087] In some embodiments, the nozzle (3) provided herein includes an outflow channel

(13) having a first restricted channel (14). In some embodiments, the first restricted channel (14) is cylindrical or conical in shape, or a combination of cylindrical and conical portions. In some embodiments, the first restricted channel (14) is cylindrical in shape. In some embodiments, the first restricted channel (14) is conical in shape. In some embodiments, the shape of the first restricted channel (14) is a combination of cylindrical and conical portions. In some embodiments, the first restricted channel (14) has a distal end opening (14d; 13d) having an inner diameter in the range of about 0.03-0.05 mm, and a proximal end opening (15p; 16d) having an inner diameter in the range of about 0.05-0.10 mm. In some embodiments, the first restricted channel (14) has a distal end opening (14d; 13d) having an inner diameter of about 0.04 mm. In some embodiments, the first restricted channel (14) has a proximal end opening (15p; 16d) having an inner diameter in the range of about 0.06-0.09 mm. In some embodiments, the first restricted channel (14) has a length in the range of 0 mm to about 10 mm. For example, in some embodiments, the first restricted channel (14) has a length of 0 mm resulting in the first restricted channel (14) being a first restricted opening. In some embodiments, the first restricted channel

(14) has a length in the range of about 2-10 mm, for example, a length of about 4 mm or about 2 mm.

[0088] In some embodiments, the nozzle (3) provided herein includes an outflow channel (13) having a first restricted channel (14) and an outflow chamber portion (15). In some embodiments, the outflow chamber portion (15) is cylindrical or conical in shape, or a combination of cylindrical and conical portions. In some embodiments, the outflow chamber portion (15) is cylindrical in shape. In some embodiments, the outflow chamber portion (15) is conical in shape. In some embodiments, the shape of the outflow chamber portion (15) is a combination of cylindrical and conical portions. In some embodiments, the outflow chamber portion (15) has a distal end opening (15d; 14p) having an inner diameter in the range of about 0.05-0.10 mm, and a proximal end opening (15p; 16d) having an inner diameter in the range of about 0.03-0.07 mm. For example, in some embodiments, the outflow chamber portion (15) has a distal end opening (15d; 14p) having an inner diameter in the range of about 0.06-0.09 mm. For example in some embodiments, the outflow chamber portion (15) has a proximal end opening (15p; 16d) having an inner diameter in the range of about 0.04-0.06 mm. In some embodiments, the outflow chamber portion (15) has a length in the range of about 2-15 mm, such as a length in the range of about 2-10 mm or in the range of about 4-8 mm. For example, in some embodiments, the outflow chamber portion (15) has a length of about 3 mm or about 4 mm. In some embodiments, the central portion of the outflow chamber portion (15) has a variable inner diameter in the range of about 0.09-0.20 mm. In some embodiments, more than 50% of the central portion of the outflow chamber portion (15) has a variable inner diameter in the range of about 0.15-0.20 mm.

[0089] In some embodiments, the nozzle (3) provided herein includes an outflow channel (13) having a first restricted channel (14), an outflow chamber portion (15), and a baffle (27). In some embodiments, the baffle (27) is positioned in the nozzle tip portion (28) of the nozzle body (12) and proximal to the dropper mouth (26). In some embodiments, the baffle (27) is cylindrical or conical in shape, or a combination of cylindrical and conical portions. In some embodiments, the baffle (27) is cylindrical in shape. In some embodiments, the baffle (27) is conical in shape.

In some embodiments, the baffle (27) has a shape that is a combination of cylindrical and conical portions. In some embodiments, the baffle (27) has an exterior diameter in the range of about 0.15-0.20 mm. In some embodiments, the baffle (27) has a length in the range of about 2-10 mm, such as a length of about 4 mm. In some embodiments, the baffle (27) comprises a second restricted channel (16). In some embodiments, the baffle (27) comprises a locking mechanism on the exterior wall that comes in contact with and locks into place within the nozzle (3) with a complimentary position along the interior wall of said nozzle (3) that defines a portion of the outflow channel (13) in said nozzle. For example, in some embodiments, the baffle (27) comprises a ridge (29a) on the exterior wall that, upon insertion into the outflow channel (13) of the nozzle (3), comes in contact with and locks into a groove (29b) that is located in the complimentary position along the interior wall of the nozzle (3) that defines a portion of the outflow channel (13) in said nozzle. In some embodiments, the baffle (27) comprises two or more ridges (29a), such as three more ridges (29a) on the exterior wall that come in contact with and lock into two or more grooves (29b), such as three or more grooves (29b) located in the complimentary positions along the interior wall of the nozzle (3) defining a portion of the outflow channel (13) in said nozzle. In some embodiments, the ridge (29) on the exterior wall of the baffle (27) is located about the circumference on the exterior wall of the baffle (27).

[0090] In some embodiments, the nozzle (3) provided herein includes an outflow channel (13) having a first restricted channel (14), an outflow chamber portion (15), and a baffle (27), wherein the baffle (27) comprises a second restricted channel (16). In some embodiments, the nozzle (3) provided herein includes an outflow channel (13) having a first restricted channel (14), an outflow chamber portion (15), and a second restricted channel (16), such as exclusive of a baffle (27). In some embodiments, the second restricted channel (16) is cylindrical or conical in shape, or a combination of cylindrical and conical portions. In some embodiments, the second restricted channel (16) is cylindrical in shape. In some embodiments, the second restricted channel (16) is conical in shape. In some embodiments, the shape of the second restricted channel (16) is a combination of cylindrical and conical portions. In some embodiments, the second restricted channel (16) has a distal end opening (16d; 15p) having an inner diameter in the range of about 0.03-0.07 mm, and a proximal end opening (16p, 13p) having an inner diameter in the range of about 0.03-0.05 mm. For example, in some embodiments, the second restricted channel (16) has a distal end opening (16d; 15p) having an inner diameter in the range of about 0.04-0.06 mm. For example, in some embodiments, the second restricted channel (16) has a proximal end opening (16p, 13p) having an inner diameter of about 0.04 mm. In some embodiments, the second restricted channel (16) has a length in the range of 0 mm to about 10 mm. For example, in some embodiments, the second restricted channel (16) has a length of 0 mm resulting in the second restricted channel (16) being a second restricted opening. In some embodiments, the second restricted channel (16) has a length of about 4-10 mm, such as a length of about 4 mm or about 2 mm.

[0091] In some embodiments, the nozzle (3) provided herein includes an outflow channel (13) having a first restricted channel (14), an outflow chamber portion (15), a baffle (27), and optionally, a dimple (17), wherein the baffle (27) comprises a second restricted channel (16). In some embodiments, the nozzle (3) provided herein includes an outflow channel (13) having a first restricted channel (14), an outflow chamber portion (15), a second restricted channel (16), and optionally, a dimple (17). In some embodiments, the nozzle (3) provided herein includes the dimple (17). In some embodiments, the dimple (17) is complimentary in shape and size to the elevated protrusion (23). In some embodiments, the dimple (17) is hemispherical in shape and complimentary to that of elevated protrusion (23), wherein the largest interior diameter of the dimple (17) is proximal to the dropper mouth (26). In some embodiments, the dimple (17) has a variable interior diameter ranging from 0.03 mm at the portion adjacent to the second restricted channel to 0.19 mm at the portion most proximal to the dropper mouth (26). In some embodiments, the dimple (17) has a distal end opening (17d; 16p) having an inner diameter in the range of about 0.03-0.07 mm, and proximal end opening (17p, 13p) having an inner diameter in the range of about 0.10-0.18 mm. For example, in some embodiments, the dimple (17) has a distal end opening (17d; 16p) having an inner diameter in the range of about 0.04-0.06 mm. For example, in some embodiments, the dimple (17) has a proximal end opening (17p, 13p) having an inner diameter in the range of about 0.12-0.17 mm. In some embodiments, the elevated protrusion (23) has a length in the range of about 0.1-1 mm.

[0092] In some embodiments, the nozzle (3) provided herein includes an outflow channel (13) having a first restricted channel (14), an outflow chamber portion (15), and a second restricted channel (16), wherein the most proximal portion of the second restricted channel (16) is the dimple (17). In some embodiments, the second restricted channel (16) has a distal end opening (16d; 15p) having an inner diameter in the range of about 0.03-0.07 mm, an intermediate end opening (16i; 17d) having an inner diameter in the range of about 0.03-0.07 mm, and a proximal end opening (16p; 17p) having an inner diameter in the range of about 0.10-0.18 mm. For example, in some embodiments, the second restricted channel (16) has a distal end opening (16d; 15p) having an inner diameter in the range of about 0.04-0.06 mm. For example, in some embodiments, the second restricted channel (16) has an intermediate end opening (16i; 17d) having an inner diameter in the range of about 0.04-0.06 mm. For example, in some embodiments, the second restricted channel (16) has a proximal end opening (16p; 17p; 13p) having an inner diameter in the range of about 0.12-0.17 mm. In some embodiments, the second restricted channel (16) has a length in the range of 0 mm to about 10 mm. For example, in some embodiments, the second restricted channel (16) has a length of 0 mm resulting in the second restricted channel (16) being a second restricted opening. In some embodiments, the second restricted channel (16) has a length of about 4-10 mm, such as a length of about 4 mm or about 2 mm.

[0093] In some embodiments, the nozzle (3) provided herein includes a dropper mouth (26). In some embodiments, the most proximal end of the outflow channel (13), where the drops to be released are formed. In some embodiments, the diameter of the dropper mouth (26) is circular and/or its diameter is in the range of 1 to 5 mm, such as its diameter is in the range of 2 to 3 mm, for example, in the range of 2.0 to 2.6 mm, or in the range of about 2.0 to 2.4 mm..

Container (Bottle)

[0094] In some embodiments, the container (2) of the eye drop dispenser (1) provided herein includes the bottle (5) and the neck (6). In some embodiments, the bottle (5) provided herein has a rounded top (7) and indents (8) on the sides (see FIG. 3B, relative to FIG. 3A, which has a flat base and cylindrical sides). FIG. 3A illustrates a container comprising a bottle and a neck, wherein 70% or more of the middle portion of the bottle sides are cylindrical and 70% or more of the bottom surface of the bottle (i.e., the surface opposite the neck of the container) is a flat surface. FIG. 3B illustrates a container (2) comprising a bottle (5) and a neck (6), wherein the middle portion of the bottle sides has 2 or more indents (8), and 70% or more of the bottle surface opposite the neck (6) of the bottle (5), the rounded top (7), which is the bottle surface opposite the neck of the container, is a rounded surface.

[0095] In some embodiments, the inclusion of the rounded top (7) provides a less rigid bottle

(5), and therefore adds increased functionality, such as ease of use in topically administering a liquid composition (e.g., less force required to squeeze the bottle to provide a drop). In some embodiments, the inclusion of the rounded top (7) reduces the pressure required to express a droplet, which would be of great value for subjects, such as subjects suffering from arthritis in the hands and fingers. The rounded shape of the rounded top (7) is configured such that it cannot support the entire structure of the eye drop dispenser (1) in an upright position. In some embodiments, the inclusion of indents (8), such as two indents on opposite sides of the bottle (5), facilitates intuitive and correct holding of the bottle (5) and ease of use.

[0096] In some embodiments, the container (2) of the eye drop dispenser (1) provided herein includes the bottle (5) and the neck (6). In some embodiments, the bottle (5) provided herein has an interior diameter in the range of about 15-20 mm. In some embodiments, the bottle (5) provided herein has an interior diameter at the upper third or the lower third of the bottle (5) in the range of about 15-20 mm. For example, in some embodiments, the bottle (5), such as at the upper third or the lower third of the bottle (5), has an interior diameter of about 15 mm, about 16 mm, about 17 mm, about 18 mm, about 19 mm, or about 20 mm. In some embodiments, the bottle (5) provided herein has an exterior diameter in the range of about 17-22 mm. For example, in some embodiments, the bottle (5) has an exterior diameter of about 17 mm, about 18 mm, about 19 mm, about 20 mm, about 21 mm, or about 22 mm. In some embodiments, the bottle (5) provided herein has indents (8) on the sides of said bottle (5). In some embodiments, the bottle (5) has an interior diameter at the level of the indents (8) that is 1-5 mm less than the interior diameter at the upper third or the lower third of the bottle (5). For example, in some embodiments, the bottle (5) has an interior diameter at the level of the indents (8) that is 1 mm less, 2 mm less, 3 mm less, 4 mm less, or 5 mm less, than the interior diameter at the upper third or the lower third of the bottle (5). In some embodiments, the bottle (5) provided herein has a length in the range of about 20-25 mm, such as a length of about 20 mm, about 21 mm, about 22 mm, about 23 mm, about 24 mm, or about 25 mm. In some embodiments, the bottle (5) provided herein has a portion proximate the opening of said bottle (5) that extends into the neck (6) of the container. For example, in some embodiments, the extended portion of the bottle (5) has a length of at least 2 mm, such as a length of at least 5 mm, for example, a length in the range of about 2-15 mm. In some embodiments, the bottle (5) provided herein has an interior fill volume in the range of about 1-10 mL. For example, in some embodiments, the bottle (5) has an interior fill volume of about 1 mL, about 2 mL, about 3 mL, about 5 mL, or about 10 mL. In some embodiments, the bottle (5) is manufactured, at least partially, of a flexible polymer, for example, a flexible thermoplastic polymer. In some embodiments, the bottle (5) is deformable by the exertion of force from a subject’s finger tips. [0097] In some embodiments, the bottle (5) provided herein has two indents (8) positioned in the middle portion (e.g., in the middle 50% of the bottle (5)) along the sides of the bottle (5). For example, in some embodiment, the bottle (5) has three indents (8) positioned in the middle portion along the sides of said bottle (5), or has four indents (8) positioned in the middle portion along the sides of said bottle (5). In some embodiments, the indents (8) have a shape complimentary to finger and/or thumb tips of a subject. In some embodiments, the indents (8) have a gripping texture on the outer surface of said bottle to facilitate grasping and/or holding of the bottle (5) by the subject.

[0098] In some embodiments, the bottle (5) provided herein has a rounded top end (7) that is positioned opposite the neck of the container (2). In some embodiments, the rounded top end (7) is a rounded surface on the bottle (5). For example, in some embodiments, 70-95% or more of the rounded top end (7) of the bottle (5) is a rounded surface, such as 70% or more, 80% or more, or 90% or more, of the rounded top end (7) of the bottle (5) is a rounded surface. In some embodiments, the rounded top end (7) of the bottle (5) is incapable of maintaining the eye drop dispenser (1) in an upright position. For example, the rounded surface of the rounded top end (7) of the bottle (5) is such that the rounded top end (7) is incapable of maintaining the eye drop dispenser (1) in an upright position. In some embodiments, the rounded top end (7) is deformable upon the exertion of force by a subject, such as when a subject exerts a force at the indents (8) (e.g., squeezes the bottle (5) at the indents (8)). In some embodiments, this added flexibility resulting from the deformation at the rounded top end (7) lessens the amount of force required to topically administer a drop from the eye drop dispenser (1), relative to a dispenser have a flat top end (7) (e.g., can maintain the eye drop dispenser in an upright position), for example, lessens the amount of required force by about 10-50%, relative to a dispenser have a flat top end (7).

[0099] In some embodiments, the container (2) of the eye drop dispenser (1) provided herein includes the bottle (5) and the neck (6), wherein the bottle (5) is detachably connected to the neck (6). For example, the bottle (5) may have threads that screw into complimentary threading in the base of the neck (6), or there may be a snapping function that allows the bottle (5) to snap into the base of the neck (6). In some embodiments, the bottle (5) is permanently fixed to the neck (6), or the bottle (5) and neck (6) are manufactured as one single unit. In some embodiments, the neck (6) provided herein has a variable exterior diameter ranging from about 10 mm to about 20 mm, such as a variable exterior diameter ranging from about 12 mm to about 17 mm. For example, in some embodiments, the distal exterior diameter of the neck (6) is in the range of about 15-20 mm, such as about 17 mm. In some embodiments, for example, the proximal exterior diameter of the neck (6) is about 12 mm. In some embodiments, the neck (6) has a length in the range of about 18-25 mm, such as a length of about 20 mm. In some embodiments, the neck (6) has a connecting portion for physically connecting the container (2) to the nozzle (3). For example, in some embodiments, the connecting portion on the neck (6) for physically connecting the container (2) to the nozzle (3) is located on the exterior surface of said neck (6). In some embodiments, the connecting portion on the exterior surface of the neck (6) for physically connecting the container (2) to the nozzle (3) is a threaded portion. In some embodiments, the neck (6) has a threaded portion on its exterior surface to physically connect the container (2) to the nozzle (3). In some embodiments, the threaded portion of the neck (6) has an exterior diameter in the range of about 10-15 mm, such as an exterior diameter of about 12 mm. In some embodiments, the threaded portion of the neck (6) has a length in the range of about 8-15 mm, such as a length of about 10 mm. In some embodiments, the connecting portion on the exterior surface of the neck (6) for physically connecting the container (2) to the nozzle (3) is a snapping portion.

[00100] In some embodiments, the container (2) of the eye drop dispenser (1) provided herein includes the bottle (5), wherein said bottle (5) comprises a liquid phase (9) and a gaseous phase (10). In some embodiments, the liquid phase (9) within the bottle (5) is an aqueous liquid composition. In some embodiments, the liquid phase (9) within the bottle (5) is a non-aqueous liquid composition. In some embodiments, the liquid phase (9) within the bottle (5) comprises a semifluorinated alkane. In some embodiments, the liquid phase (9) within the bottle (5) consists of a semifluorinated alkane.

Base Support (Cap/Lid)

[00101] In some embodiments, the eye drop dispenser (1) provided herein includes a base support (4), which also functions as a cap or lid to the container (2) of said eye drop dispenser (1). However, as the bottle (5) has a rounded top (7), it is upon the base support (4) that the entire structure of the eye drop dispenser (1) can be placed on to keep the eye drop dispenser (1) in an upright, inverted position. The bottle (5) may be attached to the base support(4) in an “up-side- down manner”. The base bottom (20) of the base support (4) has an exterior diameter that is bigger in diameter than the exterior diameter of the base opening (22) of the base support (4). In some embodiments, the interior of the base support (4) further includes, optionally, an elevated protrusion (22), or an elevated nipple, that is centrally located on the interior surface of the base bottom (20) of said base support (4), which may function to form a seal with the nozzle (3) when the container (2) is attached to the base support (4), thereby preventing leakage of the liquid phase in the container (2), such as a liquid composition comprising SFAs.

[00102] In some embodiments, the eye drop dispenser (1) provided herein includes a combination of a container (2), a nozzle (3), and a base support (4), wherein the base support (4) has an interior portion comprising a first connector receptacle (18), a nozzle body receptacle (19), and optionally, an elevated protrusion (23). In some embodiments, the first connector receptacle (18) connects to the neck (6) of the container (2), such as detachably connects to the neck (6) of the container (2). In some embodiments, the first connector receptacle (18) comprises a connecting structure to facilitate connecting to the neck (6) of the container (2). For example, in some embodiments, the connecting structure of the first connector receptacle (18) is a threading structure or is a snapping structure. In some embodiments, the first connector receptacle (18) has an interior diameter in the range of about 10-15 mm, such as an interior diameter of about 12 mm. For example, in some embodiments, the first connector receptacle (18) is threaded and has an interior diameter in the range of about 10-15 mm, such as an interior diameter of about 12 mm. In some embodiments, the first connector receptacle (18) has a length in the range of about 8-15 mm, such as a length of about 10 mm. One embodiment of the eye drop dispenser (1) provided herein, showing the container (2) attached to the base support (4), is shown in FIG. 4A. Another embodiment of the base support (4) provided herein is shown in FIG. 4B. Another embodiment of the eye drop dispenser (1) provided herein, showing the container (2) attached to the base support (4), is shown in FIG. 4C.

[00103] FIG. 4A illustrates an embodiment of an eye drop dispenser (1), wherein the eye drop dispenser (1) comprises a container (2) in physical and fluid connection with a nozzle (3), and wherein the container is detachably connected to a base support (4). In some embodiments, the container (2) of said eye drop dispenser (1) comprises a bottle (5) having a neck (6), two or more indents (8) on the sides of the bottle (5), and a rounded top end (7) opposite the neck (6) of said bottle (5). In some embodiments, the bottle (5) comprises an interior volume adapted to be partially filled with a liquid phase (9) and a gaseous phase (10) filling the remainder of the interior volume at a pressure above ambient pressure, wherein the neck (6) connects said bottle (5) to said nozzle (3). In some embodiments, the nozzle (3) of said eye drop dispenser (1) comprises a nozzle connector (11) and a nozzle body (12), wherein the nozzle connector (11) attaches the neck (6) of said container (2) to the nozzle (3), and wherein the nozzle body (12) further comprises an outflow channel (13). In some embodiments, the outflow channel (13) comprises a first restricted channel (14), an outflow chamber portion (15), a second restricted channel (16), and optionally, a dimple (17). In some embodiments, the base support (4) comprises: an interior portion, comprising a first connector receptacle (18), a nozzle body receptacle (19), and an elevated protrusion (23) capable of physical communication with said nozzle body (12), such as physical communication with the nozzle tip portion (28) of said nozzle body (12); and an exterior portion, comprising a base bottom (20), a base side (21), and a base opening (22) capable of connecting to the neck (6) of said container (2); wherein said base bottom (20) is configured to support the eye drop dispenser (1) in an upright, inverted position, and has a diameter greater than the diameter of the base side (21).

[00104] FIG. 4B illustrates a base support having an interior portion that has a first connector receptacle (18), a nozzle body receptacle (19), and an elevated protrusion (23) capable of physical communication with said nozzle body (12), such as physical communication with the nozzle tip portion (28) of said nozzle body (12); and an exterior portion that has a base bottom (20), a base side (21), and a base opening (22) capable of connecting to the neck (6) of said container (2), wherein said base bottom (20) is configured to support the eye drop dispenser (1) in an upright, inverted position, and has a diameter greater than the diameter of the base side (21).

[00105] FIG. 4C illustrates an embodiment of an eye drop dispenser (1), wherein the nozzle (3) of the eye drop dispenser (1) is sealed by the interior surface of the base support (4), wherein the nozzle (3) is exclusive of the optional dimple (17), and the base support (4) has a flat elevated protrusion (23) capable of physical communication with said nozzle body (12), such as physical communication with the nozzle tip portion (28) of said nozzle body (12), or is exclusive of an elevated protrusion.

[00106] In some embodiments, the base support (4) provided herein includes a nozzle body receptacle (19), wherein the nozzle body receptacle (19) is in a shape complementary to the shape of the nozzle body (12). In some embodiments, the nozzle body receptacle (19) is in a shape complementary to at least the nozzle tip portion (28) of the nozzle body (12). In some embodiments, the nozzle body receptacle (19) is cylindrical or conical in shape, complimentary to a portion of or all of the nozzle body (12). In some embodiments, the nozzle body receptacle (19) is cylindrical in shape. In some embodiments, the nozzle body receptacle (19) is conical in shape. In some embodiments, the shape of the nozzle body receptacle (19) is complimentary to a portion of or all of the nozzle body (12), such as complimentary to the portion proximal to the dropper mouth of the nozzle body (12). In some embodiments, the nozzle body receptacle (19) is cylindrical has an interior diameter in the range of about 5-10 mm. In some embodiments, the nozzle body receptacle (19) has a length in the range of about 8-15 mm, such as a length of about 12 mm or about 10 mm.

[00107] In some embodiments, the interior portion of the base support (4) provided herein optionally includes an elevated protrusion (23). In some embodiments, the interior portion of the base support (4) provided herein includes the elevated protrusion (23). In some embodiments, the elevated protrusion (23) comes in physical contact with the most proximal portion of the nozzle (3), such as physical contact with the dropper mouth (26) or physical contact with the nozzle tip portion (28), when the base support (4) is attached to the container (2), for example physically sealing the outflow channel (13) such that no liquid phase can escape the container (2). In some embodiments the elevated protrusion (23) slightly deforms the most proximal portion of the nozzle (3), such as slightly deforms the dropper mouth (26) or the nozzle tip portion (28), when the base support (4) is attached to the container (2), for example slightly deforming and physically sealing the outflow channel (13) such that no liquid phase can escape the container (2). In some embodiments, the interior of the base support (4) has an elevated protrusion (23) that is centrally positioned on the interior surface of the base bottom (20). In some embodiments, the elevated protrusion (23) is complimentary in shape and size to the dimple (17). In some embodiments, the elevated protrusion (23) is hemispherical in shape and complimentary to that of the dimple (17).

In some embodiments, the elevated protrusion (23) has a variable exterior diameter ranging from 0.03 mm at the tip to 0.19 mm at the base of said elevated protrusion (23). In some embodiments, the elevated protrusion (23) has a length in the range of about 0.1-1 mm. In some embodiments, the elevated protrusion (23) is rigid. In some embodiments, the elevated protrusion (23) is deformable when placed in physical contact with the nozzle (3) upon closing the eye drop dispenser to seal the interior contents.

[00108] In some embodiments, the eye drop dispenser (1) provided herein includes a combination of a container (2), a nozzle (3), and a base support (4), wherein the base support (4) has an exterior portion comprising a base bottom (20), a base support side (21), a base support opening (22), and optionally, a base lip edge (25). In some embodiments, the base support (4) has an overall vertical length in the range of about 20-30 mm, such as an overall vertical length in the range of about 25-30 mm. For example, in some embodiments, the base support (4) has an overall vertical length of about 27 mm. In some embodiments, the base support (4) is cylindrical or conical in shape. In some embodiments, the base support (4) is cylindrical in shape. In some embodiments, the base support (4) is conical in shape. In some embodiments, the base support (4) is conical in shape, having an increasing exterior diameter traversing from the base support opening (22) towards to the base bottom (20).

[00109] In some embodiments, the base support (4) provided herein includes a flat base bottom (20) surface. In some embodiments, the flat base bottom (20) is configured to support the eye dropper dispenser (1) in an upright, inverted position, wherein the gaseous phase (10) is above the flat base bottom (20). In some embodiments, the base support side (21) is cylindrical in shape and the base bottom (20) has an exterior diameter equal to or greater than the exterior diameter of said base support side (21). In some embodiments, the base support side (21) is cylindrical in shape and the base bottom (20) has an exterior diameter in the range of between 1- 40% greater than the exterior diameter of said base support side (21). For example, in some embodiments, the base support side (21) is cylindrical in shape and the base bottom (20) has an exterior diameter at least 10% greater than the exterior diameter of said base support side (21), such as an exterior diameter at least 20% greater or at least 30% greater than the exterior diameter of said base support side (21). In some embodiments, the base support side (21) is conical in shape, having an increasing exterior diameter traversing from the base support opening (22) towards to the base bottom (20), and the base bottom (20) has an exterior diameter equal to or greater than largest exterior diameter of said base support side (21). In some embodiments, the base support side (21) is conical in shape, having an increasing exterior diameter traversing from the base support opening (22) towards to the base bottom (20), and the base bottom (20) has an exterior diameter in the range of between 1-40% greater than largest exterior diameter of said base support side (21). For example, in some embodiments, the base support side (21) is conical in shape, having an increasing exterior diameter traversing from the base support opening (22) towards to the base bottom (20), and the base bottom (20) has an exterior diameter at least 10% greater than largest exterior diameter of said base support side (21), such as at least 20% greater or at least 30% greater than largest exterior diameter of said base support side (21). In some embodiments, the base bottom (20) has an exterior diameter in the range of about 18-30 mm, such as 20-30 mm, 19-25 mm, 20-28 mm, or 21-26 mm, such that the exterior diameter is in the range of between 1-40% greater than the exterior diameter of said base support side (21).

[00110] In some embodiments, the base support (4) provided herein includes a flat base bottom (20) surface and a base support side (21). In some embodiments, the base support side (21) is cylindrical or conical in shape. In some embodiments, the base support side (21) is cylindrical in shape. In some embodiments, the base support side (21) is conical in shape. In some embodiments, the base support side (21) is conical in shape, having an increasing exterior diameter traversing from the base support opening (22) towards to the base bottom (20). In some embodiments, the base support side (21) has a vertical length in the range of about 20-30 mm, such as a vertical length in the range of about 25-30 mm, for example, about 27 mm. In some embodiments, the base support side (21) is cylindrical in shape and has an exterior diameter in the range of about 15-20 mm, such as an exterior diameter of about 18 mm. In some embodiments, the base support side (21) is conical in shape, having an increasing exterior diameter traversing from the base support opening (22) towards to the base bottom (20), wherein the exterior diameter increases from 15 mm to 20 mm, such as increases from 15 mm to 18 mm or increases from 18 mm to 20 mm.

[00111] In some embodiments, the base support (4) provided herein includes a flat base bottom (20) surface, a base support side (21), and a base support opening (22). In some embodiments, the base support opening (22) has an inner diameter in the range of about 15-28 mm, such as an inner diameter of about 18 mm. In some embodiments, the base support (4), optionally, has a base lip edge (25). In some embodiments, the base support (4) has a base lip edge (25). In some embodiments, the base lip edge (25) has an exterior diameter equal to or greater than the exterior diameter of the base support side (21) proximal to the base support opening (22). In some embodiments, the base lip edge (25) has an exterior diameter is about 1- 15% greater than the exterior diameter of the base support side (21) proximal to the base support opening (22), such as at least 5% greater or at least 10 % greater than the exterior diameter of the base support side (21) proximal to the base support opening (22).

Filling and Sealing Process

[00112] In some embodiments, the process provided herein of fdling an eye drop dispenser (1) with a liquid composition includes i) providing the eye drop dispenser (1) provided herein; ii) fdling a bottle (5) of a container (2) with the liquid composition, wherein the container (2) comprises the bottle (5), a neck (6), and a rounded top (7) surface that is opposite the neck (6), and wherein the neck (6) is above a rounded top (7) of said bottle (5) during the fdling; iii) attaching a nozzle (3) to the neck (6) of the container (2); iv) applying a pressure above ambient pressure to the contents within the bottle (5) of said container (2); v) while maintaining the pressure above ambient pressure, attaching a base support (4) to the neck (6) to seal the liquid composition inside the bottle (5) of said container (2). In some embodiments, the process further comprises positioning the fdled eye drop dispenser (1) in an upright, inverted position such that the eye drop dispenser (1) is supported by the base support (4). In some embodiments, the process further comprises packaging the fdled eye drop dispenser (1) with the bottle (5) of the eye drop dispenser (1) above the base support (4). In some embodiments, the liquid composition comprises a semifluorinated alkane. In some embodiments, the this process will eliminate requiring a subject to create a negative pressure in the bottle before use, particularly in situations where the liquid composition is or comprises a semifluorinated alkane.

[00113] For example, in some embodiments, the process of fdling includes i) holding the bottle (5) in an upright position, such that the rounded top end (7) is below the neck (6); ii) fdling the bottle (5) with a liquid composition, such as with 3 mL of SFAs; iii) attaching the nozzle (3) to the neck (6); iv) applying pressure to the bottle (5) before the attaching the base support (4); v) turning the eye drop dispenser (1) in an upright, inverted position; and vi) boxing the eye drop dispenser (1), such that the entire structure of the eye drop dispenser (1) is supported on the base bottom surface (20) of said base support (4) and the top end (7) is above the neck (6). The process of fdling, in some embodiments, is shown in FIGS. 5A-5D, which illustrate a series of steps in fdling and creating a vacuum in an eye drop dispenser. In some embodiments, step 1 of the process includes fdling the bottle (5) of the container (2) with a liquid composition (FIG. 5A), step 2 includes attaching the nozzle (3) to container (2) (FIG. 5B), step 3 includes applying pressure to the contents within the bottle (5) of the container (2) and attaching the base support (4) to said container (2) to seal the pressurized contents in the bottle (5) (FIG. 5C), and step 4 includes positioning the eye drop dispenser (1) in an upright position such that the eye drop dispenser (1) is supported by the bottom surface (20) of the base support (4) (FIG. 5D).

[00114] In some embodiments, upon opening the pressurized, upright, inverted eye drop dispenser (1), external air pressure will instantaneously be sucked into the container (2) and bottle (5) and equalize the internal pressure. This opening process will automatically restrict the flow of the SFAs drop and the subject can directly administer one or more drops of the liquid composition contained within the container (2) with “soft pressure” to release 1 drop at a time, e.g., less pressure than required of an eye drop dispenser lacking the nozzle (3), bottle (5), or base support (4), as provided herein.

[00115] In some embodiments, as illustrated in FIGS. 6A-6C, the process of opening an eye drop dispenser disconnects, or unseals the nozzle tip portion and the dropper mouth from the interior surface of the base support. For example, as shown in FIG. 6A, the nozzle of the eye drop dispenser is sealed closed with the interior surface of the base support with the liquid composition contained within in the bottle under a slight pressure (pressurized liquid composition). Upon detaching the container from the base support, FIG. 6B (step 1), the nozzle is unsealed and the pressure is released and external air pressure enters the eye drop dispenser, FIG. 6C (step 2) showing an expanded view of the nozzle upon opening in step 1, illustrating the external air pressure entering into the nozzle from the environment.

Methods of Dispensing

[00116] In some embodiments, the method provided herein of topical administration of a liquid composition pressurized above ambient pressure from an eye drop dispenser (1) includes i) providing the eye drop dispenser (1) provided herein; ii) positioning said eye drop dispenser (1) such that the rounded top (7) is positioned above the base support (4); iii) detaching the base support (4) from the neck (6) of said container (2), wherein the detachment decreases the pressure within said container (2) below ambient pressure; iv) grasping and applying pressure at the indents (8) on the sides of said bottle (5), to dispense one drop of the liquid composition at a time from the container (2); v) releasing the grasped pressure at the indents (8) on the sides of said bottle (5) thereby decreasing the pressure within said container (2) below ambient pressure. In some embodiments, during each step of said method, the rounded top (7) is positioned above the base support (4). In some embodiments, the less than ambient pressure is maintained in the bottle (5), the container (2), or the eye drop dispenser (1), even if the rounded top (7) is not positioned above the base support (4), such as is positioned below the base support (4), or positioned at the same level as the base support (4), for a period of time. In some embodiments, the period of time is between 1-60 seconds. In some embodiments, the period of time is between 0-10 minutes, such as 1 ,2 ,3, 4, 5, 6, 7, 8, 9, or 10 min. In some embodiments, the liquid composition comprises a semifluorinated alkane.

[00117] In some embodiments, the method provided herein of topical administration of a liquid composition pressurized at or below ambient pressure from an eye drop dispenser (1) includes i) providing the eye drop dispenser (1) provided herein; ii) positioning the eye drop dispenser (1) such that the rounded top (7) is positioned below the base support (4); iii) removing the base support (4) from the container (2) of said eye drop dispenser (1); iv) exerting a force to the sides of the bottle (5) while holding the container (2) in an upright position such that the outflow channel (13) in the nozzle (3) is not in contact with the liquid composition in said bottle (3), thereby reducing the interior volume of said bottle (5) and forcing a portion of the gaseous phase (10) in said bottle (5) out of the container (2) and into the environment; v) inverting the container (2) to an inverted position, while maintaining the exerted force, such that the liquid composition comes in contact with the outflow channel (13); vi) releasing said first force from the bottle (5) of the container (2) at least partly, thereby reducing the pressure inside the bottle (5) below ambient pressure; and vii) exerting a second force to sides of the bottle (5) of the container (2), while still holding the container (2) in the inverted position in which the liquid composition is in contact with the outflow channel (13), thereby raising the pressure inside the interior volume of the bottle (5) above ambient pressure and releasing the liquid composition dropwise from the nozzle (3) of the eye drop dispenser (1). In some embodiments, the exerting of the first force to sides of the bottle (5) of the eye drop dispenser (1) is applied at the indents (8) on the sides of said bottle (5). In some embodiments, the exerting of the second force to sides of the bottle (5) of the eye drop dispenser (1) is applied at the indents (8) on the sides of said bottle (5). In some embodiments, once the less than ambient pressure is achieved, it is maintained in the bottle (5), the container (2), or the eye drop dispenser (1), even if the rounded top (7) is not positioned above the base support (4), such as is positioned below the base support (4), or positioned at the same level as the base support (4), for a period of time. In some embodiments, the period of time is between 1-60 seconds. In some embodiments, the period of time is between 0-10 minutes, such as 1 ,2 ,3, 4, 5, 6, 7, 8, 9, or 10 min. In some embodiments, the liquid composition comprises a semifluorinated alkane. In some embodiments, the method provided herein is topically administering a liquid composition pressurized at ambient pressure from an eye drop dispenser

(1). In some embodiments, the method provided herein is topically administering a liquid composition pressurized below ambient pressure from an eye drop dispenser (1).

[00118] In some embodiments, the method provided herein of topical administration of a liquid composition includes: a) providing an eye drop dispenser (1), comprising a container (2) with an interior volume partially filled with a liquid composition (9) and a gaseous phase (10) filling the remainder of the interior volume at ambient pressure, the container (2) having a bottle (5), and a nozzle (3) in physical connection and in fluid communication with the interior volume of the container (2), comprising an outflow channel (13), connecting the interior volume of the container (2) to the environment; b) exerting a first force to the bottle (5) of the container

(2) of the eye drop dispenser (1) while holding the eye drop dispenser (1) in an upright position in which the outflow channel (13) is not in contact with the liquid composition (9), thereby reducing the interior volume of the container (2) and forcing the gaseous phase (10) of the interior volume at least partially out of the eye drop dispenser (1) into the environment; c) inverting the eye drop dispenser (1) to an inverted position in which the liquid composition (9) is in contact with the outflow channel (13); d) releasing said first force from the bottle (5) of the container (2) at least partly, thereby reducing the pressure inside the container (2) below ambient pressure; and e) exerting a second force to the bottle (5) of the container (2), while still holding the eye drop dispenser (1) in the inverted position in which the liquid composition (9) is in contact with the outflow channel (13), thereby raising the pressure inside the interior volume of the container (2) above ambient pressure and releasing the liquid composition (9) dropwise from the nozzle (3) of the eye drop dispenser (1).

[00119] In some embodiments, the method provided herein further includes i) inverting the eye drop dispenser (1) as to return to an upright position, thereby sucking air from environment through the outflow channel (13) into the interior volume, as to effect underpressure relief in the eye dropper dispense (1); ii) closing and storing the eye drop dispenser (1). In some embodiments, the method may be used more than once pre delivery of a single dose of the liquid composition.

[00120] The eye drop dispenser (1) provided herein, and methods of fdling and using the same, facilitates dispensing of semifluorinated alkanes in smaller volumes and in a more controlled fashion than currently possible thereby greatly reducing wastage and cost [00121] The eye drop dispenser (1) provided herein, and methods of fdling and using the same, facilitates dispensing of smaller volume for water-based eye drops, at a level achieved by more expensive and complicated piezoelectric dispensers. This has the additional advantage of reducing the risk of over-dispensing potent drugs, thereby reducing potential side effects.

[00122] Dimensions of the base support (4), the nozzle (3), and the container (2) attached to the nozzle (3), and provided in FIGS. 7-9, respectively.

[00123] FIG. 7 illustrates a base support (4). In some embodiments, for example, the base support (4) includes base support sides (21) having a length of about 27 mm, a base support opening (22) having an inner diameter of about 18 mm, and optionally, a base lip edge having an inner diameter of about 20 mm.

[00124] FIG. 8 illustrates a nozzle (3). In some embodiments, for example, the nozzle (3) includes a nozzle connector (11) and a nozzle body (12). In some embodiments, the nozzle body

(12) includes an outflow channel (13) having a first restricted channel (14) distal to the dropper mouth (26), a baffle (27) positioned in the nozzle tip portion (28) and proximal to the dropper mouth (26), wherein the baffle (27) includes a second restricted channel (16), and an outflow chamber portion (15) between and in communication with the first restricted channel (14) and the second restricted channel (16) within said baffle (27). In some embodiments, the outflow channel

(13) may be cylindrical or conical in shape, or a combination of cylindrical and conical portions, has an overall length in the range of about 10-20 mm, and has a variable inner diameter in the range or 0.03-0.20 mm. In some embodiments, the first restricted channel (14), which may be cylindrical or conical in shape, and has a distal end opening (14d; 13d) having an inner diameter in the range of about 0.03-0.05 mm, such as 0.04 mm, a proximal end opening (14p; 15d) having an inner diameter in the range of about 0.05-0.10 mm, such as about 0.06-0.09 mm, and a length in the range of about 0 mm to 10 mm, such as about 4 mm or about 2 mm. In some embodiments, the outflow chamber portion (15) may be cylindrical or conical in shape, or a combination of cylindrical and conical portions and has a distal end opening (15d; 14p) having an inner diameter in the range of about 0.05-0.10 mm, such as in the range of about 0.06-0.09 mm, a proximal end opening (15p; 16d) having an inner diameter in the range of about 0.03-0.07 mm, such as in the range of about 0.04-0.06 mm, and a length in the range of about 2-15 mm, wherein the central portion of the outflow chamber portion (15) has an inner diameter ranging from 0.09-0.20 mm. In some embodiments, the baffle (27) may be cylindrical or conical in shape, or a combination of cylindrical and conical portions, and has an exterior diameter in the range of about 0.15-0.20 mm and a length in the range of about 2-10 mm, and includes a second restricted channel (16), which may be cylindrical or conical in shape, or a combination of cylindrical and conical portions, and has a distal end opening (16d; 15p) having an inner diameter in the range of about 0.03-0.07 mm, such as in the range of about 0.04-0.06 mm, and a proximal end opening (16p, 13p) having an inner diameter in the range of about 0.03-0.05 mm, such as about 0.04 mm, and a length in the range of about 0 mm to 10 mm, such as about 4 mm.

[00125] FIG. 9 illustrates a container (2) of an eye dispenser (1) that is attached to a nozzle (3). In some embodiments, the container (2) has a bottle (5) having an interior diameter of about 18 mm, an exterior diameter of about 20 mm, and a length of about 22 mm. In some embodiments, the bottle (5) has a portion proximate the opening of the bottle (5) that extends into the neck (6), wherein the length of said extended portion is at least 2 mm in length. In some embodiments, the container (2) has a neck (6) having a variable exterior diameter ranging from about 12 mm to about 17 mm, and a length of about 20 mm, wherein the neck (6) is in physical communication with the bottle (5) and the nozzle (3), and wherein said neck has features suitable for connecting the container (2) to a base support (4) so as to enclose the nozzle (3), for example, threads to screw into the base support (4), or a snapping configuration. In some embodiments, the threaded portion of the neck has an exterior diameter of about 12 mm and a length of about 10 mm. In some embodiments, the nozzle (3) attaches directly to the neck (6) of the container (2) via a nozzle connector (11), wherein the nozzle body (12) is cylindrical or conical in shape along the portion distal to the dropper mouth (26) and hemispherical in shape within the nozzle tip portion (28). In some embodiments, the nozzle body (12) has a length of about 12 mm, and an exterior diameter in the range of about 5-10 mm, and the nozzle connector (11) has an exterior diameter of about 12 mm.

Examples

Exemplary Embodiments

[00126] In certain embodiments, one or more than one (including for instance all) or the following further embodiments may comprise each of the other embodiments or parts thereof. [00127] Al. In an embodiment, an eye drop dispenser (1), comprising a container (2), a nozzle (3), and a base support (4), wherein: i) the nozzle (3) comprises a nozzle body (12), said nozzle body (12) comprising an outflow channel (13) that connects the interior volume in the container (2) to the environment, said outflow channel (13) comprising: a) a first restricted channel (14); and b) a second restricted channel (16); and ii) the base support (4) comprises: a) a base side (21); and b) a base bottom (20) configured to support the eye drop dispenser (1) in an upright, inverted position, and has a diameter greater than the diameter of the base side (21).

[00128] A2. In an embodiment, an eye drop dispenser (1), comprising a container (2), a nozzle (3), and a base support (4), wherein: i) the nozzle (3) comprises a nozzle body (12), said nozzle body (12) comprising an outflow channel (13) that connects the interior volume in the container (2) to the environment, said outflow channel (13) comprising: a) a first restricted channel (14); and b) a baffle (27) configured with a second restricted channel (16); and ii) the base support (4) comprises: a) a base side (21); and b) a base bottom (20) configured to support the eye drop dispenser (1) in an upright, inverted position, and has a diameter greater than the diameter of the base side (21).

[00129] A3. In an embodiment, an n eye drop dispenser (1), comprising a container (2), a nozzle (3), and a base support (4), wherein: i) the nozzle (3) comprises a nozzle body (12), said nozzle body (12) comprising an outflow channel (13) that connects the interior volume in the container (2) to the environment, said outflow channel (13) comprising: a) a first restricted channel (14); b) an outflow chamber portion (15); and c) a baffle (27) configured with a second restricted channel (16) in fluid connection with the outflow chamber portion (15) and the environment; and ii) the base support (4) comprises: a) a base side (21); and b) a base bottom (20) configured to support the eye drop dispenser (1) in an upright, inverted position, and has a diameter greater than the diameter of the base side (21).

[00130] A4. In an embodiment, an eye drop dispenser (1), comprising a container (2), a nozzle (3), and a base support (4), wherein: i) the nozzle (3) comprises a nozzle body (12), said nozzle body (12) comprising an outflow channel (13) that connects the interior volume in the container (2) to the environment, said outflow channel (13) comprising: a) a first restricted channel (14); b) an outflow chamber portion (15); and c) a baffle (27) configured with a second restricted channel (16) in fluid connection with the outflow chamber portion (15) and the environment; and ii) the base support (4) comprises: a) an interior portion comprising a first connector receptacle (18), a nozzle body receptacle (19), and an elevated protrusion (23) capable of physical communication with said nozzle body (12); and b) an exterior portion comprising a base bottom (20) and a base side (21), and a base opening (22) capable of connecting to the neck (6) of said container (2); wherein said base bottom (20) is configured to support the eye drop dispenser (1) in an upright, inverted position, and has a diameter greater than the diameter of the base side (21).

[00131] A5. In an embodiment, an eye drop dispenser (1), comprising a container (2), a nozzle (3), and a base support (4), wherein: i) the container (2) is in physical and fluid connection with the nozzle (3), and wherein said container (2) is detachably connected to the base support (4), and wherein said container (2) comprises:

A) a bottle (5) having two or more indents (8) on the sides of the bottle (5) and a rounded top end (7) opposite the neck (6) of the bottle (5), said bottle (5) further comprising an interior volume adapted to be partially filled with a liquid phase (9) and a gaseous phase (10) filling the remainder of the interior volume at a pressure above ambient pressure; and

B) a neck (6) connecting the bottle (5) to the nozzle (3); ii) the nozzle (3) comprises a nozzle connector (11) and a nozzle body (12), wherein:

A) the nozzle connector (11) attaches the neck (6) of said container (2) to the nozzle (3); and

B) the nozzle body (12) comprises an outflow channel (13), said outflow channel (13) comprising: a) a first restricted channel (14); b) an outflow chamber portion (15); c) a second restricted channel (16); and d) optionally, a dimple (17); iii) the base support (4) comprises:

A) an interior portion comprising a first connector receptacle (18), a nozzle body receptacle (19), and an elevated protrusion (23) capable of physical communication with said nozzle body (12); and

B) an exterior portion comprising a base bottom (20), a base side (21), and a base opening (22) capable of connecting to the neck (6) of said container (2); wherein said base bottom (20) is configured to support the eye drop dispenser (1) in an upright, inverted position, and has a diameter greater than the diameter of the base side (21).

[00132] A6. In an embodiment, the eye drop dispenser of any one of embodiments A1-A5, wherein the bottle (5) has an interior diameter in the range of about 15-20 mm.

[00133] A7. In an embodiment, the eye drop dispenser of any one of embodiments A1-A6, wherein the bottle (5) has an interior diameter of about 18 mm.

[00134] A8. In an embodiment, the eye drop dispenser of any one of embodiments A1-A7, wherein the bottle (5) has an exterior diameter in the range of about 17-22 mm.

[00135] A9. In an embodiment, the eye drop dispenser of any one of embodiments A1-A8, wherein the bottle (5) has an exterior diameter of about 20 mm.

[00136] A10. In an embodiment, the eye drop dispenser of any one of embodiments A1-A9, wherein the bottle (5) has an interior diameter at the level of the indents (8) is 1-5 mm less than the interior diameter at the upper third or the lower third of the bottle (5).

[00137] All. In an embodiment, the eye drop dispenser of any one of embodiments A1-A10, wherein the bottle (5) has a length in the range of about 20-25 mm.

[00138] A12. In an embodiment, the eye drop dispenser of any one of embodiments Al-Al 1, wherein the bottle (5) has a length of about 22 mm.

[00139] A13. In an embodiment, the eye drop dispenser of any one of embodiments A1-A12, wherein the bottle (5) has a portion proximate the opening of said bottle (5) that extends into the neck (6) of the container.

[00140] A14. In an embodiment, the eye drop dispenser of any one of embodiments A1-A13, wherein the extended portion of the bottle (5) has a length of at least 2 mm.

[00141] A15. In an embodiment, the eye drop dispenser of any one of embodiments A1-A14, wherein the extended portion of the bottle (5) has a length in the range of about 2-15 mm.

[00142] A16. In an embodiment, the eye drop dispenser of any one of embodiments A1-A15, wherein the extended portion of the bottle (5) has a length of at least 5 mm.

[00143] A17. In an embodiment, the eye drop dispenser of any one of embodiments A1-A16, wherein the bottle (5) has an interior fdl volume in the range of about 1-10 mL.

[00144] A18. In an embodiment, the eye drop dispenser of any one of embodiments Al-Al 7, wherein the bottle (5) has an interior fdl volume of about 1 mL.

[00145] A19. In an embodiment, the eye drop dispenser of any one of embodiments A1-A18, wherein the bottle (5) has an interior fdl volume of about 2 mL.

[00146] A20. In an embodiment, the eye drop dispenser of any one of embodiments A1-A19, wherein the bottle (5) has an interior fdl volume of about 3 mL.

[00147] A21. In an embodiment, the eye drop dispenser of any one of embodiments A1-A20, wherein the bottle (5) has an interior fdl volume of about 5 mL. [00148] A22. In an embodiment, the eye drop dispenser of any one of embodiments A1-A21, wherein the bottle (5) has two indents (8) positioned in the middle portion along the sides of the bottle (5).

[00149] A23. In an embodiment, the eye drop dispenser of any one of embodiments A1-A22, wherein the bottle (5) has three indents (8) positioned in the middle portion along the sides of said bottle (5).

[00150] A24. In an embodiment, the eye drop dispenser of any one of embodiments A1-A23, wherein the bottle (5) has four indents (8) positioned in the middle portion along the sides of said bottle (5).

[00151] A25. In an embodiment, the eye drop dispenser of any one of embodiments A1-A24, wherein the bottle (5) has a rounded top end (7) that is positioned opposite the neck of the container (2).

[00152] A26. In an embodiment, the eye drop dispenser of any one of embodiments A1-A25, wherein the rounded top end (7) is a rounded surface on the bottle (5).

[00153] A27. In an embodiment, the eye drop dispenser of any one of embodiments A1-A26, wherein 70-95% or more of the rounded top end (7) of the bottle (5) is a rounded surface.

[00154] A27. In an embodiment, the eye drop dispenser of any one of embodiments A1-A27, wherein 70% or more of the rounded top end (7) of the bottle (5) is a rounded surface.

[00155] A29. In an embodiment, the eye drop dispenser of any one of embodiments A1-A28, wherein 80% or more of the rounded top end (7) of the bottle (5) is a rounded surface.

[00156] A30. In an embodiment, the eye drop dispenser of any one of embodiments A1-A29, wherein 90% or more of the rounded top end (7) of the bottle (5) is a rounded surface.

[00157] A31. In an embodiment, the eye drop dispenser of any one of embodiments A1-A30, wherein the rounded top end (7) of the bottle (5) is incapable of maintaining the eye drop dispenser (1) in an upright position.

[00158] A32. In an embodiment, the eye drop dispenser of any one of embodiments A1-A31, wherein the neck (6) has a variable exterior diameter ranging from about 10 mm to about 20 mm. [00159] A33. In an embodiment, the eye drop dispenser of any one of embodiments A1-A32, wherein the neck (6) has a variable exterior diameter ranging from about 12 mm to about 17 mm. [00160] A34. In an embodiment, the eye drop dispenser of any one of embodiments A1-A33, wherein the distal exterior diameter of the neck (6) is in the range of about 15-20 mm.

[00161] A35. In an embodiment, the eye drop dispenser of any one of embodiments A1-A34, wherein the distal exterior diameter of the neck (6) is about 17 mm.

[00162] A36. In an embodiment, the eye drop dispenser of any one of embodiments A1-A35, wherein the proximal exterior diameter of the neck (6) is about 12 mm.

[00163] A37. In an embodiment, the eye drop dispenser of any one of embodiments A1-A36, wherein the neck (6) has a length in the range of about 18-25 mm. [00164] A38. In an embodiment, the eye drop dispenser of any one of embodiments A1-A37, wherein the neck (6) has a length of about 20 mm.

[00165] A39. In an embodiment, the eye drop dispenser of any one of embodiments A1-A38, wherein the neck (6) has a connecting portion for physically connecting the container (2) to the nozzle (3).

[00166] A40. In an embodiment, the eye drop dispenser of any one of embodiments A1-A39, wherein the connecting portion on the neck (6) for physically connecting the container (2) to the nozzle (3) is located on the exterior surface of said neck (6).

[00167] A41. In an embodiment, the eye drop dispenser of any one of embodiments A1-A40, wherein the connecting portion on the exterior surface of the neck (6) for physically connecting the container (2) to the nozzle (3) is a threaded portion.

[00168] A42. In an embodiment, the eye drop dispenser of any one of embodiments A1-A41, wherein the neck (6) has a threaded portion on its exterior surface to physically connect the container (2) to the nozzle (3).

[00169] A43. In an embodiment, the eye drop dispenser of any one of embodiments A1-A42, wherein the threaded portion of the neck (6) has an exterior diameter in the range of about 10-15 mm.

[00170] A44. In an embodiment, the eye drop dispenser of any one of embodiments A1-A43, wherein the threaded portion of the neck (6) has an exterior diameter of about 12 mm.

[00171] A45. In an embodiment, the eye drop dispenser of any one of embodiments A1-A44, wherein the threaded portion of the neck (6) has a length in the range of about 8-15 mm.

[00172] A46. In an embodiment, the eye drop dispenser of any one of embodiments A1-A45, wherein the threaded portion of the neck (6) has a length of about 10 mm.

[00173] A47. In an embodiment, the eye drop dispenser of any one of embodiments A1-A46, wherein the connecting portion on the exterior surface of the neck (6) for physically connecting the container (2) to the nozzle (3) is a snapping portion.

[00174] A48. In an embodiment, the eye drop dispenser of any one of embodiments A1-A47, wherein the liquid phase (9) within the bottle (5) is a non-aqueous liquid composition.

[00175] A49. In an embodiment, the eye drop dispenser of any one of embodiments A1-A48, wherein the liquid phase (9) within the bottle (5) comprises a semifluorinated alkane.

[00176] A50. In an embodiment, the eye drop dispenser of any one of embodiments A1-A49, wherein the nozzle connector (11) attaches the neck (6) of the container (2) to the nozzle (3). [00177] A51. In an embodiment, the eye drop dispenser of any one of embodiments A1-A50, wherein the nozzle connector (11) has an exterior diameter in the range of about 10-15 mm. [00178] A52. In an embodiment, the eye drop dispenser of any one of embodiments A1-A51, wherein the nozzle connector (11) has an exterior diameter of about 12 mm. [00179] A53. In an embodiment, the eye drop dispenser of any one of embodiments A1-A52, wherein the nozzle body (12) is cylindrical or conical in shape along the portion distal to the dropper mouth (26).

[00180] A54. In an embodiment, the eye drop dispenser of any one of embodiments A1-A53, wherein the nozzle body (12) has an exterior diameter in the range of about 5-10 mm.

[00181] A55. In an embodiment, the eye drop dispenser of any one of embodiments A1-A54, wherein the nozzle body (12) has a length in the range of about 8-15 mm.

[00182] A56. In an embodiment, the eye drop dispenser of any one of embodiments A1-A55, wherein the nozzle body (12) has a length of about 12 mm.

[00183] A57. In an embodiment, the eye drop dispenser of any one of embodiments A1-A56, wherein the nozzle body (12) has a length of about 10 mm.

[00184] A58. In an embodiment, the eye drop dispenser of any one of embodiments A1-A57, wherein the nozzle body (12) is hemispherical in shape along the nozzle tip portion (28).

[00185] A59. In an embodiment, the eye drop dispenser of any one of embodiments A1-A58, wherein the outflow channel (13) connects the interior volume in the container (2) to the environment.

[00186] A60. In an embodiment, the eye drop dispenser of any one of embodiments A1-A59, wherein the outflow channel (13) connects the interior volume in the bottle (5) to the environment.

[00187] A61. In an embodiment, the eye drop dispenser of any one of embodiments A1-A60, wherein the outflow channel (13) comprises a first restricted channel (14) distal to the dropper mouth (26) and a second restricted channel (16) proximal to the dropper mouth (26).

[00188] A62. In an embodiment, the eye drop dispenser of any one of embodiments A1-A61, wherein the outflow channel (13) comprises: i) a first restricted channel (14) distal to the dropper mouth (26); ii) a second restricted channel (16) proximal to the dropper mouth (26); iii) an outflow chamber portion (15) in fluid communication between the first restricted channel (14) and the second restricted channel (16); and iv) optionally, a dimple (17) in fluid communication between the second restricted channel (16) and the dropper mouth (26).

[00189] A63. In an embodiment, the eye drop dispenser of any one of embodiments A1-A62, wherein the outflow channel (13) comprises a first restricted channel (14) distal to the dropper mouth (26) and a baffle (27) proximal to the dropper mouth (26), wherein the baffle (27) is configured with a second restricted channel (16).

[00190] A64. In an embodiment, the eye drop dispenser of any one of embodiments A1-A63, wherein the outflow channel (13) comprises: i) a first restricted channel (14) distal to the dropper mouth (26); ii) a baffle (27) proximal to the dropper mouth (26), wherein the baffle (27) is configured with a second restricted channel (16); iii) an outflow chamber portion (15) in fluid communication between the first restricted channel (14) and the second restricted channel (16) of the baffle (27); and iv) optionally, a dimple (17) in fluid communication between the second restricted channel (16) of the baffle (27) and the dropper mouth (26).

[00191] A65. In an embodiment, the eye drop dispenser of any one of embodiments A1-A64, wherein the outflow channel (13) comprises the dimple (17).

[00192] A66. In an embodiment, the eye drop dispenser of any one of embodiments A1-A65, wherein the dimple (17) is hemispherical in shape.

[00193] A67. In an embodiment, the eye drop dispenser of any one of embodiments A1-A66, wherein the dimple (17) has a variable interior diameter ranging from 0.03 mm to 0.19 mm. [00194] A68. In an embodiment, the eye drop dispenser of any one of embodiments A1-A67, wherein the dimple (17) has a length in the range of about 0.1-1 mm.

[00195] A69. In an embodiment, the eye drop dispenser of any one of embodiments A1-A68, wherein the outflow channel (13) is cylindrical or conical in shape, or a combination of cylindrical and conical portions.

[00196] A70. In an embodiment, the eye drop dispenser of any one of embodiments A1-A69, wherein the outflow channel (13) has an overall length in the range of about 10-20 mm.

[00197] A71. In an embodiment, the eye drop dispenser of any one of embodiments A1-A70, wherein the outflow channel (13) has an overall length in the range of about 10-15 mm.

[00198] A72. In an embodiment, the eye drop dispenser of any one of embodiments A1-A71, wherein the outflow channel (13) has an overall length of about 10 mm.

[00199] A73. In an embodiment, the eye drop dispenser of any one of embodiments A1-A72, wherein the outflow channel (13) has an overall length of about 12 mm.

[00200] A74. In an embodiment, the eye drop dispenser of any one of embodiments A1-A73, wherein the outflow channel (13) has a variable inner diameter in the range or 0.03-0.20 mm [00201] A75. In an embodiment, the eye drop dispenser of any one of embodiments A1-A74, wherein the first restricted channel (14) is cylindrical or conical in shape, or a combination of cylindrical and conical portions.

[00202] A76. In an embodiment, the eye drop dispenser of any one of embodiments A1-A75, wherein the first restricted channel (14) has a distal end opening (14d; 13d) having an inner diameter in the range of about 0.03-0.05 mm, and a proximal end opening (14p; 15d) having an inner diameter in the range of about 0.05-0.10 mm.

[00203] A77. In an embodiment, the eye drop dispenser of any one of embodiments A1-A76, wherein the first restricted channel (14) has a distal end opening (14d; 13d) having an inner diameter of about 0.04 mm. [00204] A78. In an embodiment, the eye drop dispenser of any one of embodiments A1-A77, wherein the first restricted channel (14) has a proximal end opening (14p; 15d) having an inner diameter in the range of about 0.06-0.09 mm.

[00205] A79. In an embodiment, the eye drop dispenser of any one of embodiments A1-A78, wherein the first restricted channel (14) has a length in the range of 0 mm to about 10 mm. [00206] A80. In an embodiment, the eye drop dispenser of any one of embodiments A1-A79, wherein the first restricted channel (14) has a length in the range of about 2-10 mm.

[00207] A81. In an embodiment, the eye drop dispenser of any one of embodiments A1-A80, wherein the first restricted channel (14) has a length of about 4 mm.

[00208] A82. In an embodiment, the eye drop dispenser of any one of embodiments A1-A81, wherein the first restricted channel (14) has a length of about 2 mm.

[00209] A83. In an embodiment, the eye drop dispenser of any one of embodiments A1-A82, wherein the outflow chamber portion (15) is cylindrical or conical in shape, or a combination of cylindrical and conical portions.

[00210] A84. In an embodiment, the eye drop dispenser of any one of embodiments A1-A83, wherein the outflow chamber portion (15) has a distal end opening (15d; 14p) having an inner diameter in the range of about 0.05-0.10 mm, and a proximal end opening (15p; 16d) having an inner diameter in the range of about 0.03-0.07 mm.

[00211] A85. In an embodiment, the eye drop dispenser of any one of embodiments A1-A84, wherein the outflow chamber portion (15) has a distal end opening (15d; 14p) having an inner diameter in the range of about 0.06-0.09 mm.

[00212] A86. In an embodiment, the eye drop dispenser of any one of embodiments A1-A85, wherein the outflow chamber portion (15) has a proximal end opening (15p; 16d) having an inner diameter in the range of about 0.04-0.06 mm.

[00213] A87. In an embodiment, the eye drop dispenser of any one of embodiments A1-A86, wherein the outflow chamber portion (15) has a length in the range of about 2-15 mm.

[00214] A88. In an embodiment, the eye drop dispenser of any one of embodiments A1-A87, wherein the outflow chamber portion (15) has a length in the range of about 2-10 mm.

[00215] A89. In an embodiment, the eye drop dispenser of any one of embodiments A1-A88, wherein the outflow chamber portion (15) has a length in the range of about 4-8 mm.

[00216] A90. In an embodiment, the eye drop dispenser of any one of embodiments A1-A89, wherein the outflow chamber portion (15) has a length of about 3 mm.

[00217] A91. In an embodiment, the eye drop dispenser of any one of embodiments A1-A90, wherein the outflow chamber portion (15) has a length of about 4 mm.

[00218] A92. In an embodiment, the eye drop dispenser of any one of embodiments A1-A91, wherein the central portion of the outflow chamber portion (15) has a variable inner diameter in the range of about 0.09-0.20 mm. [00219] A93. In an embodiment, the eye drop dispenser of any one of embodiments A1-A92, wherein more than 50% of the central portion of the outflow chamber portion (15) has a variable inner diameter in the range of about 0.15-0.20 mm.

[00220] A94. In an embodiment, the eye drop dispenser of any one of embodiments A1-A93, wherein the baffle (27) is positioned in the nozzle tip portion (28) of the nozzle body (12) and proximal to the dropper mouth (26).

[00221] A95. In an embodiment, the eye drop dispenser of any one of embodiments A1-A94, wherein the baffle (27) is cylindrical or conical in shape, or a combination of cylindrical and conical portions.

[00222] A96. In an embodiment, the eye drop dispenser of any one of embodiments A1-A95, wherein the baffle (27) has an exterior diameter in the range of about 0.15-0.20 mm.

[00223] A97. In an embodiment, the eye drop dispenser of any one of embodiments A1-A96, wherein the baffle (27) has a length in the range of about 2-10 mm.

[00224] A98. In an embodiment, the eye drop dispenser of any one of embodiments A1-A97, wherein the baffle (27) has a length of about 4 mm.

[00225] A99. In an embodiment, the eye drop dispenser of any one of embodiments A1-A98, wherein the baffle (27) comprises a second restricted channel (16).

[00226] A 100. In an embodiment, the eye drop dispenser of any one of embodiments Al- A99, wherein the second restricted channel (16) is cylindrical or conical in shape, or a combination of cylindrical and conical portions.

[00227] A101. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A100, wherein the second restricted channel (16) has a distal end opening (16d; 15p) having an inner diameter in the range of about 0.03-0.07 mm, and a proximal end opening (16p; 13p) having an inner diameter in the range of about 0.03-0.05 mm.

[00228] A 102. In an embodiment, the eye drop dispenser of any one of embodiments Al- A101, wherein the second restricted channel (16) has a distal end opening (16d; 15p) having an inner diameter in the range of about 0.04-0.06 mm.

[00229] A 103. In an embodiment, the eye drop dispenser of any one of embodiments Al- A102, wherein the second restricted channel (16) has a proximal end opening (16p; 13p) having an inner diameter of about 0.04 mm.

[00230] A 104. In an embodiment, the eye drop dispenser of any one of embodiments Al- A103, wherein the second restricted channel (16) has a length in the range of 0 mm to about 10 mm.

[00231] A 105. In an embodiment, the eye drop dispenser of any one of embodiments Al- A104, wherein the second restricted channel (16) has a length of about 4-10 mm.

[00232] A 106. In an embodiment, the eye drop dispenser of any one of embodiments Al- A105, wherein the second restricted channel (16) has a length of about 4 mm. [00233] A 107. In an embodiment, the eye drop dispenser of any one of embodiments Al- A106, wherein the interior of the base support (4) has a first connector receptacle (18), a nozzle body receptacle (19), and optionally, an elevated protrusion (23).

[00234] A 108. In an embodiment, the eye drop dispenser of any one of embodiments Al- A107, wherein the first connector receptacle (18) connects to the neck (6) of the container (2). [00235] A 109. In an embodiment, the eye drop dispenser of any one of embodiments Al- A108, wherein the first connector receptacle (18) detachably connects to the neck (6) of the container (2).

[00236] A110. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A109, wherein the first connector receptacle (18) comprises a connecting structure to facilitate connecting to the neck (6) of the container (2).

[00237] A111. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A110, wherein the connecting structure of the first connector receptacle (18) is a threading structure.

[00238] A112. In an embodiment, the eye drop dispenser of any one of embodiments Al- A111, wherein the connecting structure of the first connector receptacle (18) is a snapping structure.

[00239] A113. In an embodiment, the eye drop dispenser of any one of embodiments Al- A112, wherein the first connector receptacle (18) has an interior diameter in the range of about 10-15 mm.

[00240] A114. In an embodiment, the eye drop dispenser of any one of embodiments Al- A113, wherein the first connector receptacle (18) has an interior diameter of about 12 mm.

[00241] A115. In an embodiment, the eye drop dispenser of any one of embodiments Al- A114, wherein the first connector receptacle (18) is threaded and has an interior diameter in the range of about 10-15 mm.

[00242] A116. In an embodiment, the eye drop dispenser of any one of embodiments Al- A115, wherein the first connector receptacle (18) is threaded and has an interior diameter of about 12 mm.

[00243] A117. In an embodiment, the eye drop dispenser of any one of embodiments Al- A116, wherein the first connector receptacle (18) has a length in the range of about 8-15 mm. [00244] A118. In an embodiment, the eye drop dispenser of any one of embodiments Al- A117, wherein the first connector receptacle (18) has a length of about 10 mm.

[00245] A119. In an embodiment, the eye drop dispenser of any one of embodiments Al- A118, wherein the nozzle body receptacle (19) is in a shape complementary to the shape of the nozzle body (12). [00246] A 120. In an embodiment, the eye drop dispenser of any one of embodiments Al- A119, wherein the nozzle body receptacle (19) is in a shape complementary to at least the nozzle tip portion (28) of the nozzle body (12).

[00247] A 121. In an embodiment, the eye drop dispenser of any one of embodiments Al- A120, wherein the nozzle body receptacle (19) is cylindrical or conical in shape, complimentary to a portion of or all of the nozzle body (12).

[00248] A 122. In an embodiment, the eye drop dispenser of any one of embodiments Al- A121, wherein the nozzle body receptacle (19) is cylindrical has an interior diameter in the range of about 5-10 mm.

[00249] A 123. In an embodiment, the eye drop dispenser of any one of embodiments Al- A122, wherein the nozzle body receptacle (19) has a length in the range of about 8-15 mm. [00250] A 124. In an embodiment, the eye drop dispenser of any one of embodiments Al- A123, wherein the nozzle body receptacle (19) has a length of about 12 mm.

[00251] A125. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A124, wherein the nozzle body receptacle (19) has a length of about 10 mm.

[00252] A 126. In an embodiment, the eye drop dispenser of any one of embodiments Al- A125, wherein the interior of the base support (4) has an elevated protrusion (23).

[00253] A 127. In an embodiment, the eye drop dispenser of any one of embodiments Al- A126, wherein the elevated protrusion (23) is centrally positioned on the interior surface of the base bottom (20).

[00254] A128. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A127, wherein the elevated protrusion (23) is complimentary in shape and size to the dimple (17). [00255] A 129. In an embodiment, the eye drop dispenser of any one of embodiments Al- A128, wherein the elevated protrusion (23) is hemispherical in shape and complimentary to that of the dimple (17).

[00256] A 130. In an embodiment, the eye drop dispenser of any one of embodiments Al- A129, wherein the elevated protrusion (23) has a variable exterior diameter ranging from 0.03 mm at the tip to 0.19 mm at the base of said elevated protrusion (23).

[00257] A131. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A130, wherein the elevated protrusion (23) has a length in the range of about 0.1-1 mm.

[00258] A132. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A131, wherein the exterior of the base support (4) has a base bottom (20), a base support side (21), a base support opening (22), and optionally, a base lip edge.

[00259] A 133. In an embodiment, the eye drop dispenser of any one of embodiments Al- A132, wherein the base support (4) has an overall vertical length in the range of about 20-30 mm. [00260] A134. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A133, wherein the base support (4) has an overall vertical length in the range of about 25-30 mm. [00261] A135. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A134, wherein the base support (4) has an overall vertical length of about 27 mm.

[00262] A 136. In an embodiment, the eye drop dispenser of any one of embodiments Al- A135, wherein the base support (4) is cylindrical or conical in shape.

[00263] A 137. In an embodiment, the eye drop dispenser of any one of embodiments Al- A136, wherein the base support (4) is cylindrical in shape.

[00264] A138. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A137, wherein the base support (4) is conical in shape.

[00265] A 139. In an embodiment, the eye drop dispenser of any one of embodiments Al- A138, wherein the base support (4) is conical in shape, having an increasing exterior diameter traversing from the base support opening (22) towards to the base bottom (20).

[00266] A 140. In an embodiment, the eye drop dispenser of any one of embodiments Al- A139, wherein the base support side (21) is cylindrical or conical in shape.

[00267] A 141. In an embodiment, the eye drop dispenser of any one of embodiments Al- A140, wherein the base support side (21) is cylindrical in shape.

[00268] A 142. In an embodiment, the eye drop dispenser of any one of embodiments Al- A141, wherein the base support side (21) is conical in shape.

[00269] A 143. In an embodiment, the eye drop dispenser of any one of embodiments Al- A142, wherein the base support side (21) is conical in shape, having an increasing exterior diameter traversing from the base support opening (22) towards to the base bottom (20).

[00270] A 144. In an embodiment, the eye drop dispenser of any one of embodiments Al- A143, wherein the base support side (21) has a vertical length in the range of about 20-30 mm. [00271] A145. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A144, wherein the base support side (21) has a vertical length in the range of about 25-30 mm. [00272] A 146. In an embodiment, the eye drop dispenser of any one of embodiments Al- A145, wherein the base support side (21) has a vertical length of about 27 mm.

[00273] A 147. In an embodiment, the eye drop dispenser of any one of embodiments Al- A146, wherein the base support side (21) is cylindrical in shape and has an exterior diameter in the range of about 15-20 mm.

[00274] A148. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A147, wherein the base support side (21) is cylindrical in shape and has an exterior diameter of about 18 mm.

[00275] A 149. In an embodiment, the eye drop dispenser of any one of embodiments Al- A148, wherein the base support side (21) is conical in shape, having an increasing exterior diameter traversing from the base support opening (22) towards to the base bottom (20), wherein the exterior diameter increases from 15 mm to 20 mm. [00276] A 150. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A149, wherein the base support side (21) is conical in shape, having an increasing exterior diameter traversing from the base support opening (22) towards to the base bottom (20), wherein the exterior diameter increases from 15 mm to 18 mm.

[00277] A151. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A150, wherein the base support side (21) is conical in shape, having an increasing exterior diameter traversing from the base support opening (22) towards to the base bottom (20), wherein the exterior diameter increases from 18 mm to 20 mm.

[00278] A152. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A151, wherein the base support opening (22) has an inner diameter in the range of about 15-28 mm.

[00279] A 153. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A152, wherein the base support opening (22) has an inner diameter of about 18 mm.

[00280] A154. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A153, wherein the base support (4) has a flat base bottom (20) surface.

[00281] A155. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A154, wherein the flat base bottom (20) is configured to support the eye dropper dispenser (1) in an upright, inverted position, wherein the gaseous phase (10) is above the flat base bottom (20). [00282] A 156. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A155, wherein the base support side (21) is cylindrical in shape and the base bottom (20) has an exterior diameter equal to or greater than the exterior diameter of said base support side (21). [00283] A 157. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A156, wherein the base support side (21) is cylindrical in shape and the base bottom (20) has an exterior diameter in the range of between 1-40% greater than the exterior diameter of said base support side (21).

[00284] A158. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A157, wherein the base support side (21) is cylindrical in shape and the base bottom (20) has an exterior diameter at least 10% greater than the exterior diameter of said base support side (21). [00285] A 159. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A158, wherein the base support side (21) is cylindrical in shape and the base bottom (20) has an exterior diameter at least 20% greater than the exterior diameter of said base support side (21). [00286] A 160. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A159, wherein the base support side (21) is cylindrical in shape and the base bottom (20) has an exterior diameter at least 30% greater than the exterior diameter of said base support side (21). [00287] A161. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A160, wherein the base support side (21) is conical in shape, having an increasing exterior diameter traversing from the base support opening (22) towards to the base bottom (20), and the base bottom (20) has an exterior diameter equal to or greater than largest exterior diameter of said base support side (21).

[00288] A 162. In an embodiment, the eye drop dispenser of any one of embodiments Al- A161, wherein the base support side (21) is conical in shape, having an increasing exterior diameter traversing from the base support opening (22) towards to the base bottom (20), and the base bottom (20) has an exterior diameter in the range of between 1-40% greater than largest exterior diameter of said base support side (21).

[00289] A 163. In an embodiment, the eye drop dispenser of any one of embodiments Al- A162, wherein the base support side (21) is conical in shape, having an increasing exterior diameter traversing from the base support opening (22) towards to the base bottom (20), and the base bottom (20) has an exterior diameter at least 10% greater than largest exterior diameter of said base support side (21).

[00290] A 164. In an embodiment, the eye drop dispenser of any one of embodiments Al- A163, wherein the base support side (21) is conical in shape, having an increasing exterior diameter traversing from the base support opening (22) towards to the base bottom (20), and the base bottom (20) has an exterior diameter at least 20% greater than largest exterior diameter of said base support side (21).

[00291] A 165. In an embodiment, the eye drop dispenser of any one of embodiments Al- A164, wherein the base support side (21) is conical in shape, having an increasing exterior diameter traversing from the base support opening (22) towards to the base bottom (20), and the base bottom (20) has an exterior diameter at least 30% greater than largest exterior diameter of said base support side (21).

[00292] A 166. In an embodiment, the eye drop dispenser of any one of embodiments Al- A165, wherein the base support (4) has a base lip edge (25).

[00293] A 167. In an embodiment, the eye drop dispenser of any one of embodiments Al- A166, wherein the base lip edge (25) has an exterior diameter equal to or greater than the exterior diameter of the base support side (21) proximal to the base support opening (22).

[00294] A 168. In an embodiment, the eye drop dispenser of any one of embodiments Al- A167, wherein the base lip edge (25) has an exterior diameter is about 1-15% greater than the exterior diameter of the base support side (21) proximal to the base support opening (22).

[00295] A 169. In an embodiment, the eye drop dispenser of any one of embodiments Al- A168, wherein the base lip edge (25) has an exterior diameter at least 5% greater than the exterior diameter of the base support side (21) proximal to the base support opening (22).

[00296] A 170. In an embodiment, the eye drop dispenser of any one of embodiments Al- A169, wherein the base lip edge (25) has an exterior diameter at least 10% greater than the exterior diameter of the base support side (21) proximal to the base support opening (22). [00297] A171. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A170, wherein the baffle (27) comprises a locking mechanism on the exterior wall that comes in contact with and locks into place within the nozzle (3) with a complimentary position along the interior wall of said nozzle (3) that defines a portion of the outflow channel (13) in said nozzle. [00298] A172. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A171, wherein the baffle (27) comprises a ridge (29a) on the exterior wall that, upon insertion into the outflow channel (13) of the nozzle (3), comes in contact with and locks into a groove (29b) that is located in the complimentary position along the interior wall of the nozzle (3) that defines a portion of the outflow channel (13) in said nozzle.

[00299] A 173. In an embodiment, the eye drop dispenser of any one of embodiments Al- A172, wherein the baffle (27) comprises two or more ridges (29a), such as three more ridges (29a) on the exterior wall that come in contact with and lock into two or more grooves (29b), such as three or more grooves (29b) located in the complimentary positions along the interior wall of the nozzle (3) defining a portion of the outflow channel (13) in said nozzle.

[00300] A174. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A173, wherein the ridge (29) on the exterior wall of the baffle (27) is located about the circumference on the exterior wall of the baffle (27).

[00301] A175. In an embodiment, the eye drop dispenser of any one of embodiments Al-

A174, wherein the elevated protrusion (23) is rigid.

[00302] A 176. In an embodiment, the eye drop dispenser of any one of embodiments Al- A174, wherein the elevated protrusion (23) is deformable when placed in physical contact with the nozzle (3) upon closing the eye drop dispenser to seal the interior contents.

[00303] B 1. In an embodiment, a process of filling an eye drop dispenser (1) with a liquid composition, wherein the method comprises: i) providing the eye drop dispenser (1) of any one of embodiments A1-A170; ii) filling a bottle (5) of a container (2) with the liquid composition, wherein the container (2) comprises the bottle (5), a neck (6), and a rounded top (7) surface that is opposite the neck (6), and wherein the neck (6) is above a rounded top (7) of said bottle (5) during the filling; iii) attaching a nozzle (3) to the neck (6) of the container (2); iv) applying a pressure above ambient pressure to the contents within the bottle (5) of said container (2); v) while maintaining the pressure above ambient pressure, attaching a base support (4) to the neck (6) to seal the liquid composition inside the bottle (5) of said container (2).

[00304] B2. In an embodiment, the process of filling of any one of embodiments Bl, wherein the process further comprises positioning the filled eye drop dispenser (1) in an upright, inverted position such that the eye drop dispenser (1) is supported by the base support (4). [00305] B3. In an embodiment, the process of filling of any one of embodiments B1-B2, wherein the process further comprises packaging the filled eye drop dispenser (1) with the bottle (5) of the eye drop dispenser (1) above the base support (4).

[00306] B4. In an embodiment, the process of filling of any one of embodiments B1-B3, wherein during each step of said method, the rounded top (7) is positioned above the base support

(4).

[00307] B5. In an embodiment, the process of filling of any one of embodiments B1-B4, wherein the liquid composition comprises a semifluorinated alkane.

[00308] B6. In an embodiment, the process of filling of any one of embodiments B1-B5, wherein the liquid composition consists essentially of semifluorinated alkane.

[00309] Cl . In an embodiment, a method of topical administration of a liquid composition pressurized above ambient pressure from an eye drop dispenser (1), wherein the method comprises: i) providing the eye drop dispenser (1) of any one of embodiments A1-A170; ii) positioning said eye drop dispenser (1) such that the rounded top (7) is positioned above the base support (4); iii) detaching the base support (4) from the neck (6) of said container (2), wherein the detachment decreases the pressure within said container (2) below ambient pressure; iv) grasping and applying pressure at the indents (8) on the sides of said bottle (5), to dispense one drop of the liquid composition at a time from the container (2); v) releasing the grasped pressure at the indents (8) on the sides of said bottle (5) thereby decreasing the pressure within said container (2) below ambient pressure.

[00310] C2. In an embodiment, a method of topical administration of a liquid composition at a pressure below ambient pressure from an eye drop dispenser (1), wherein the method comprises: i) providing the eye drop dispenser (1) of any one of embodiments A1-A170; ii) positioning the eye drop dispenser (1) such that the rounded top (7) is positioned below the base support (4); iii) removing the base support (4) from the container (2) of said eye drop dispenser (1); iv) exerting a force to the sides of the bottle (5) while holding the container (2) in an upright position such that the outflow channel (13) in the nozzle (3) is not in contact with the liquid composition in said bottle (3), thereby reducing the interior volume of said bottle (5) and forcing a portion of the gaseous phase (10) in said bottle (5) out of the container (2) and into the environment; v) inverting the container (2) to an inverted position, while maintaining the exerted force, such that the liquid composition comes in contact with the outflow channel (13); vi) releasing said first force from the bottle (5) of the container (2) at least partly, thereby reducing the pressure inside the bottle (5) below ambient pressure; and vii) exerting a second force to sides of the bottle (5) of the container (2), while still holding the container (2) in the inverted position in which the liquid composition is in contact with the outflow channel (13), thereby raising the pressure inside the interior volume of the bottle (5) above ambient pressure and releasing the liquid composition dropwise from the nozzle (3) of the eye drop dispenser (1).

[00311] C3. In an embodiment, the method of topical administration of any one of embodiments C1-C2, wherein the exerting of the first force to sides of the bottle (5) of the eye drop dispenser (1) is applied at the indents (8) on the sides of said bottle (5).

[00312] C4. In an embodiment, the method of topical administration of any one of embodiments C1-C3, wherein the exerting of the second force to sides of the bottle (5) of the eye drop dispenser (1) is applied at the indents (8) on the sides of said bottle (5).

[00313] C5. In an embodiment, the method of topical administration of any one of embodiments C1-C4, wherein the liquid composition comprises a semifluorinated alkane.

[00314] C6. In an embodiment, the method of topical administration of any one of embodiments C1-C5, wherein the liquid composition in the eye drop dispenser is pressurized at ambient pressure.

[00315] C7. In an embodiment, the method of topical administration of any one of embodiments C1-C5, wherein the liquid composition in the eye drop dispenser is pressurized below ambient pressure.

[00316] All publications and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference in its entirety.

[00317] It will be understood that the embodiments disclosed and defined in this specification extends to all alternative combinations of two or more of the individual features mentioned or evident from the text or drawings, and that subheadings used within this specification are for convenience purposes only, and not meant to define or limit portions of combinations with the remaining disclosure. All of these different combinations constitute various alternative aspects of the present disclosure.

[00318] The foregoing outlines features of several embodiments so that those skilled in the art may better understand the aspects of the present disclosure. Those skilled in the art should appreciate that they may readily use the present disclosure as a basis for designing or modifying other processes and structures for carrying out the same purposes and/or achieving the same advantages of the embodiments introduced herein. Those skilled in the art should also realize that such equivalent constructions do not depart from the spirit and scope of the present disclosure, and that they may make various changes, substitutions, and alterations herein without departing from the spirit and scope of the present disclosure.

[00319] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.