FIELD OF THE INVENTION

[0001] The present invention relates to a pharmaceutical kit comprising (i) a pump dispenser for dispensing multiples of a predetermined base-dosage of a liquid or paste-like pharmaceutical (ii) said liquid or paste-like pharmaceutical contained in said pump dispenser and (iii) instructions for implementing a predetermined titration scheme, wherein said titration scheme comprises the dispensing of at least two different integer multiples of said predetermined base-dosage.

[0002] The present invention also relates to the use of said kit for treating a patient.

BACKGROUND OF THE INVENTION

[0003] For certain pharmaceutical compositions, a desired dosage regime and/or a desired overall dosage cannot or should not be achieved in a single step but rather by means of incrementally increasing or decreasing the dosage from a certain predefined initial dosage to a certain predetermined final dosage and/or by means of dosing in intervals.

[0004] This increase or decrease or alternating of dosages involving at least two dosages that are different from each other is referred to as "titration" in the following. [0005] In the prior art, the titration of solid tablets is known, for example by providing a tablet of a given dosage and further providing instructions to administer fractions or multiples of said one tablet.

[0006] Titration packages comprising different tablets of increasing dosages (for example 5 mg, 10 mg, 15 mg, 20 mg) are also known from the art (see, e.g., US 2006/0278557). Therein, a titration package and method for enabling compliance with a regime of changing dosage of medication over a period of time is provided. The solid formulation package includes a backing having an array of receivers with the array including a plurality of columns and a plurality of rows. A plurality of sets of tablets are provided with each tablet in set having a common dose of medication and a different dose than a tablet of a different set.

[0007] In some cases, however, a solid formulation may not be available or may be difficult to implement. Also, in case the titration scheme comprises a large number of different dosages, manufacturing and providing a large number of different tablets may be cumbersome and ineffective. For example, according to US 2006/0278557, at least four different tablets each having a different composition need to be manufactured and packaged/provided separately.

[0008] A method of dosing liquids known in the art is a droplet dispenser. Therein, small droplets are dispensed out of a bottle having a comparatively small orifice. The volume of the droplet so dispensed is determined, within a certain margin of error, by the geometry of the orifice. In order to average fluctuations in the droplet volume, a large number of droplets needs to be dispensed and counted, for example 20 droplets. In order to achieve titration, multiples of a base-dosage would need to be dispensed rendering this system cumbersome and error-prone, for example for elderly and/or impaired patients.

OBJECTS OF THE INVENTION

[0009] Therefore, one object of the present invention is to provide a means for delivering a liquid or paste-like pharmaceutical to a patient in need thereof that allows for a high degree of flexibility in regard to how many and which multiples of a base-dosage can be administered and that allows for easy and safe dispensing of different dosages even if the patient is potentially impaired, for example in regard to vision or in regard to memory. Drawbacks and limitations posed by the prior art as discussed above should be avoided or minimized.

SUMMARY OF THE INVENTION

[0010] This object, among others, is solved by a pharmaceutical kit comprising (i) a pump dispenser for dispensing multiples of a predetermined base-dosage of a liquid or paste-like pharmaceutical (ii) said liquid or paste- like pharmaceutical contained in said pump dispenser and (iii) instructions for implementing a predetermined titration scheme, wherein said titration scheme comprises the dispensing of at least two different integer multiples of said predetermined base-dosage.

[0011] This object is also solved by the use of said kit for treating a patient. [0012] In accordance with one embodiment of the present invention, said pump dispenser comprises at least a pump head and dispensing is achieved by means of actuating said pump head of said pump dispenser.

[0013] In accordance with another embodiment of the present invention, said pump dispenser comprises at least one pump head and at least one reservoir attached thereto. Pump heads are easy to operate and are made, in one embodiment, big enough and ergonomically suitable for operation by elderly patients, visually impaired patients and/or patients who are impaired in regard to motion control.

[0014] In accordance with another embodiment of the present invention, the pump head is of the "push-plunger"-type, i.e. comprises at least one plunger or piston or actuated pusher, i.e. actuator, and at least one sealed chamber in which a pressure can be built up by means of moving said plunger/piston/ actuator.

[0015] In accordance with another embodiment of the present invention said pump dispenser comprises at least one hollow body with a chamber of a defined inner volume and a defined inner diameter. In accordance with one embodiment of the present invention, said hollow body comprises a recess that has a diameter that is larger than said inner diameter of the chamber.

[0016] In accordance with another embodiment of the present invention, said pump dispenser additionally comprises at least one ball acting as a one-way valve and at least one piston that runs inside said hollow body.

[0017] In accordance with another embodiment of the present invention, the volume as defined by the chamber inside said hollow body of the dispenser head is more than 0.1 ml or more than 0.5 ml or more than 1 ml or more than 3 ml. In accordance with another embodiment, said volume ranges from 0.1 ml to 5.0 ml or from 0.3 ml to 3 ml or from 0.5 ml to 1 ml.

[0018] In accordance with yet another embodiment of the present invention, the spout of the pump dispenser, i.e. the part of the pump head out of which the liquid or paste-like pharmaceutical is ultimately expelled is arcuate, i.e. has at least one portion that is substantially parallel to the horizontal plane and has at least one other portion that is inclined in at least a 45 degree angle relative to said horizontal plane.

[0019] In accordance with another embodiment of the present invention, the dispensing of the base-dosage is achieved by performing one stroke of an actuator or plunge or piston of the pump head. Therein, "one stroke" means one single stroke.

[0020] In accordance with one embodiment of the present invention, said liquid or paste-like pharmaceutical comprises at least one NMDA receptor antagonist and/or at least one acetylcholinesterase inhibitor and/or at least one αg/αio nicotinic receptor antagonist.

[0021] In accordance with one embodiment of the present invention, said liquid or paste-like pharmaceutical comprises at least memantine and/or neramexane and/or pharmaceutically acceptable salts thereof such as memantine HCI or neramexane mesylate.

[0022] In accordance with one embodiment of the present invention, said titration scheme comprises at least one up-titration step, i.e. comprises the dispensing of at least two or at least three or at least four increasing integer multiples of said predetermined base-dosage, for example the dispensing of at least two increasing integers of the base-dosage with said integer starting at 1.

[0023] In accordance with one embodiment of the present invention, said titration scheme comprises the dispensing of at least two or at least three or at least four decreasing integer multiples of said predetermined base-dosage. Such a titration scheme may be used for decreasing the dosage to a certain predetermined final dosage (such as for a maintenance therapy). The scheme may comprise at first the dispensing of an integer multiple ni of a base-dosage and consecutively dispensing an integer multiple n ₂ , wherein

[0024] In accordance with one embodiment of the present invention, said titration scheme comprises the dispensing of at least two or at least three or at least four alternating dosages that are different from each other. Such a titration scheme may be used for alternating between certain predetermined dosages (such as for an interval therapy). In one embodiment, each of the at least two different dosages are dispensed at least twice.

[0025] Any of the titration schemes is to be understood that an initial dosage may be administered for several consecutive days, including one week or more than a week, for example once daily for one week, before the next (different) dosage is administered, for example a higher or a lower or an alternating dosage, also for example once daily for one week.

[0026] In accordance with one embodiment of the present invention, the kit as described in any one of the aforementioned embodiments is used for the treatment of a patient. DETAILED DESCRIPTION OF THE INVENTION

[0027] In accordance with one embodiment of the present invention, "dispensing" means "actuating a pump dispenser". This is achieved, in one embodiment, by means of actuating the pump head of the pump dispenser, for example by performing one complete or one incomplete stroke of the actuator or plunge or piston of the pump head. Therein, "one" means "one single".

[0028] In accordance with one embodiment of the present invention, "predetermined" base-dosage means one specific volume that is dispensed per (incomplete or complete) stroke, for example 0.25 ml or 0.3 ml or 0.5 ml or 1 ml or 2 ml or 3 ml or 5 ml. This volume is defined by the geometry of the pump dispenser, for example of the pump head and the volume of the hollow chamber formed therein. Said predetermined base-dosage cannot be adjusted or altered by the patient.

[0029] In accordance with one embodiment, an incomplete stroke of the actuator or plunge or piston of the pump head may also be sufficient, as long as the amount of fluid dispensed per (incomplete) stroke is the same or similar. Mechanisms ensuring such a repetitively stable modus of dispensing are described below, for example starting in paragraph [0046].

[0030] In one embodiment according to the present invention, titration occurs in at least two steps of administering consecutively increasing multiple integers of the base-dosage. Such a titration regime is referred to as "up-titra- tion" and may be used, for example, for administering memantine as the active ingredient. In a specific embodiment, said integer is starting at 1 , i.e. one time the base-dosage is administered, then two times the base-dosage etc.

[0031] In another embodiment according to the present invention, titration occurs in at least two steps of administering consecutive decreasing multiple integers of a base-dosage. For example, the starting dosage may be 100 %, i.e. 4 times the base-dosage of 25 % while the following dosage is 75 %, i.e. 3 times the base-dosage of 25 %. Such a titration regime is referred to as "maintenance therapy" and may be used, for example, for administering neramexane or pharmaceutically acceptable salts thereof.

[0032] In a specific embodiment according to the present invention, titration occurs in at least three steps of administering consecutive multiple integers of the base-dosage. According to one embodiment, said integer starts at 1 and the dosage increases (i.e. 1 time the base-dosage, 2 times the base- dosage, 3 times the base-dosage, ...), while in another embodiment, the integer starts at a number ≥ 3 and the dosage decreases (i.e. 3 times the base- dosage, 2 times the base-dosage, 1 time the base-dosage).

[0033]ln yet another embodiment according to the present invention, titration occurs in at least four steps of administering consecutive multiple integers of the base-dosage with said integer starting at 1 (i.e. 1 time the base-dosage, 2 times the base-dosage, 3 times the base-dosage, 4 times the base-dosage or 4 times the base-dosage, then 3 times the base-dosage etc.), while in another embodiment, the integer starts at a number ≥ 4 and the dosage correspondingly decreases. [0034] In yet another embodiment of the invention, titration occurs in intervals with a high dosage and a subsequent lower dosage followed again by said high dosage etc.

[0035] As can be seen from the above, implementing various titration schemes by means of using one pump dispenser and simply varying the number of strokes is possible, while, at the same type working with only one base-dosage of the pharmaceutical composition (having a predetermined concentration in regard to the active ingredient).

[0036]ln accordance with the present invention, a practitioner prescribing the kit may devise individual titration schemes for individual patients while using one pump dispenser provided with one base-dosage that can therefore be manufactured and provided commercially at minimum operating expenses.

[0037] Liquid or paste-like pharmaceuticals according to the present invention may be in the form of a solution, a dispersion or an emulsion (micro- or nano- emulsions, self-emulsifying system, multiple emulsions) or in the form of a gel, paste, suspension (micro- or nano-suspension), hydrosol, liposome, mixed micells or in other forms of colloidal disperse systems such as drug loaded microparticles, nanocapsules or nanoparticles dispersed in a colloidal system or solution. Paste-like masses may display a Newtonian or a non- Newtonian flow behaviour.

[0038] Active pharmaceutical ingredients (APIs) that may be administered in accordance with such a titration scheme are or may be the following active ingredients in liquid or in paste-like form: uncompetitive channel blockers (e.g. NMDAr antabonists, e.g. amantadine, dextromethorphan, ibogaine, ketamine, phencyclidine, riluzole, memantine, neramexane), antagonists at αg/cho nicotinic receptors (e.g. neramexane), non-competitive antagonists (e.g. dizocilpine, aptiganel, remacimide), glycine antagonists (e.g. 1-aminocyclopropanecarboxylic acid (ACPC), competitive antagonists (e.g. AP7 (2-amino-7-phosphonoheptanoic acid), thrombolytics (e.g. reteplase, tenecteplase, anistreplase, streptokinase, urokinase), anticoagulants (e.g. heparin, warfarin, acenocoumarol, phenprocoumon, phenindione, argatroban, lepirudin, bivalirudin), antibiotics, corticosteroids (e.g. be- clomethasone, budesonide, betamethasone, ciclesonide, flunisolide, fluticasone, mometasone, refleponide, triamcinolone), antiplatelet agents (e.g. aspirin, clopidogrel, ticlopidine, abciximab, eptifibatide, tirofiban, cilostazol), non-stereoidal anti-inflammatories (NSAID) (e.g. salicylates (e.g. aspirin, amoxiprin, benorilate, choline magnesium salicylate, diflunisal, faislamine, methyl salicylate, magnesium salicylate, salicyl salicylate), arylalkanoic acids (e.g. diclofenac, aceclofenac, acemetacin, bromfenac, etodolac, indometacin, nabumetone, sulindac, tometin), 2-Arylpropionic acids (profens) (e.g. ibuprofen, carprofen, fenbufen, fenoporfen, flurbiprofen, ketoprofen, ketorolac, loxoprofen, naproxen, oxaprozin, tiaprofenic acid, suprofen), N-Arylanthranilic acids (fenamic acids) (e.g. mefenamic acid, meclofenamic acid), pyrazolidine derivates (e.g. phenylbutazone, azapropa- zone, metamizole, oxyphenbutazone, sulfinpyrazone), oxicams (e.g. piroxi- cam, lornoxicam, meloxicam, tenoxicam), COX-2 inhibitors (e.g. celecoxib, etoricoxib, lumiracoxib, parecoxib, rofecoxib, valdecoxib), sulphonanilides (e.g. nimesulide)), growth factors (e.g. transforming growth factor beta (TGF- β), granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), nerve growth factor (NGF), neurotro- phins, platelet derived growth factor (PDGF), erythropoietin (EPO), throm- bopoietin (TPO), myostatin (GDF-8), growth differentiation factor-9 (GDF9), acidic fibroblast growth factor (aFGF or FGF-1), basic fibroblast growth factor (bFGF or FGF-2), epidermal growth factor (EGF), hepatocyte growth factor (HGF)), immunosuppressant drugs (e.g. cyclosporine, tacrolimus, prednisolone, azathioprine, sirolimus, mycopehnolate, glatiramer acetate), antineoplastic agents (alkylating agents (e.g. cisplatin, carboplatin, oxaliplatin, mechlorethamine, cyclophosphamide, chlorambucil), anti-metabolites (e.g. azathioprine, mercaptopurine, pyrimidine), vinca alkaloids (e.g. vincristine, vinblastine, vinorelbine, vindesine), podophyllotoxin (e.g. etoposide, teni- poside), taxanes (e.g. paclitaxel), topoisomerase inhibitors (e.g. amsacrine, etoposide, etoposide phosphate, teniposide, camptothecins such as iri- notecan, topotecan), antitumor antibiotics (e.g. dactinomycin), monoclonal antibodies (e.g. trastuzumab, cetuximab, rituximab, bevacizumab)), ACE- inhibitors (e.g. captopril, zofenopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, fosinopril), Acetylcholinesterase Inhibitors (e.g. done- pezil, rivastigmine, pyridostigmine, tetrahydroaminoacridine physostigmine, galantamine, tacrine, edrophonium, neostigmine), HMG-coA reductase inhibitors (e.g. atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, simvastatin), beta-blockers (e.g. alprenolol, carteolol, levobunolol, mepin- dolol, metipranolol, nadolol, oxprenolol, penbutolol, pindolol, propranolol, sotalol, timolol, acebutolol, atenolol, betaxolol, bisoprolol, esmolol, metoprolol, nebivolol, carvedilol, celiprolol, lavetalol, butaxamin), calcium channel blockers (e.g. verapamil, gallopamil, diltiazem, nimodipine, amlodi- pine, felodipine, nicardipine, nifedipine, nisoldipine, nitrendipine, lacidipine, lercandipine), long acting nitrates (e.g. isosorbide dinitrate and mononitrate, nitroglycerin) or cholesterol-lowering agents (e.g. bezafibrate, ciprofibrate, clofibrate, gemfibrozil, fenofibrate).

[0039] According to one embodiment of the present invention, the kit comprising a liquid or paste-like pharmaceutical comprises at least one NMDA receptor antagonist. Such NMDAr antagonists may be compositions com- prising, as pharmaceutically active ingredients, memantine or neramexane or pharmaceutically acceptable salts thereof.

[0040] Another embodiment according to the present invention relates to a kit comprising a liquid or paste-like pharmaceutical comprising at least one acetylcholinesterase inhibitor (AchEI). Such acetylcholinesterase inhibitors may be compositions comprising, among others, donepezil, rivastigmine, pyridostigmine, tetrahydroaminoacridine, physostigmine, galantamine, tacrine, edrophonium, neostigmine and pharmaceutically acceptable salts thereof.

[0041] In accordance with the present invention, no restrictions are made in regard to the composition of the fluid, liquid or paste-like substance that is being dispensed, other than that the fluid, liquid or paste-like substance must comprise at least one pharmaceutically active ingredient. Otherwise, the fluid, liquid or paste-like substance may include any other solvent, solute, additive, adjuvant or excipient that is pharmaceutically acceptable. According to one embodiment water and alcohol, or mixtures thereof, are used as solvent(s).

[0042] Pump dispensers for dispensing liquids, viscous or paste-like masses, for example soap, lotion or condiments are known form the art. A simple-to- operate push plunger housed in a container is known, for example, from US 3 463 093. Another example of a general use dispensing unit is given in US 5 326 000. A dispenser or delivery apparatus for flowable media, particularly very viscous or gel-like media, specifically also comprising pharmaceuticals is disclosed in US 4 728 008. [0043] In accordance with one embodiment of the present invention, the pump dispenser comprises at least one pump head and at least one reservoir attached thereto.

[0044] According to one embodiment of the present invention, the pump head is of the "push-plunger"-type, i.e. comprises at least one plunger or piston or actuated pusher (actuator) and at least one sealed chamber in which a pressure can be built up by means of moving said plunger/piston/actuator.

[0045] Dispensing by means of the "push-plunger"-principle is seen as particularly advantageous for operation of the dispenser by visually impaired patients or patients having coordination/motion control issues as is typical for some of the indications in accordance with the present invention, for example dementia, glaucoma, Alzheimer's disease etc. Droplet dispensers for liquids as known from pharmaceutical applications employing measuring spoons and/or narrow spouts for "counting" droplets are much less suitable for these indications/applications than the pump dispenser and kit in accordance with the present invention.

[0046] In one embodiment according to the present invention, the pump dispenser dispenses said predetermined base-dosage essentially independent of the actuation path, and/or irrespective of how far the pump head has been actuated. In one embodiment, the amount of dispensed fluid is independent of how far the pump head (or, more specifically, the plunger) has been actuated once a predetermined threshold of the actuation path has been passed. [0047] In accordance with one embodiment of the present invention said threshold is defined by a recess in a chamber of the pump head of the dispenser.

[0048] There are no restrictions in regard to the specific mechanic design for achieving this dosing of one specific and predetermined base-dosage as long as the same or at least a sufficiently similar dosage is provided per at least partially executed stroke.

[0049] One possible technical realization for achieving a predetermined and reproducible dosage with one complete or one partially incomplete stroke is described in the following and illustrated by Figure 1 showing an exemplary pump head / dosage head in accordance with the afore-described embodiment of the present invention.

[0050] The pump head comprises at least one hollow body (15) with a chamber (19) of a given inner diameter di ₅ . This chamber contains the substance to be dispensed during the next cycle. This hollow body (15) also comprises a recess (20) with a diameter larger than di ₅ . The hollow body furthermore comprises a conical seat and a second channel (22). This second channel is connected to a larger reservoir of the substance to be dispensed, i.e. the reservoir of the overall dispenser.

[0051] A ball (21) is located in a conical seat of hollow body (15). Said ball (21) acts as a one-way valve and may seal off the second channel (22). Inside the hollow body (15) runs a piston (17) with a hollow stem (18) and an elastic lip at the lower end of piston (17). The hollow stem (18) comprises a first channel (27). A first spring (24) is provided between piston (17) and a shoulder of the hollow body (15). Said first spring (24) drives the piston away from the above-discussed reservoir. The hollow stem (18) has a compartment at its top to house the cone (28) and a second spring (29). This small compartment is open (35) to lead to any tube or applicator or spout for actually dispensing the fluid. Cone (28) is loaded by this second spring (29) and will close channel (27). Further details can be taken from Figure 1.

[0052] In the following, one mode of operation of this unit is explained. The cycle of dispensing the substance and refilling chamber (19) can be achieved as follows. Initially, chamber (19) is filled with the pharmaceutical substance to be dispensed. Springs (24) and (29) are not fully expanded. The second and first channels (22) and (27) are closed. The dispensing cycle is started by pushing the stem (18) into the hollow body (15). Meanwhile, piston (17) is driven further into the hollow body (15) thus increasing the chamber pressure. At the same time, spring (24) is being compressed.

[0053] At a predetermined chamber pressure, the second spring (29) yields to said chamber pressure. This "yielding" can be adjusted (or "predetermined") by choosing an appropriate second spring (29). Coincidentally with the yielding of the second spring (29), the cone (28) opens the first channel (27). The pharmaceutical substance now flows out of chamber (19) through first channel (27) and opening (35), driven by the chamber pressure. Once the elastic lower lip of piston (17) reaches the recess (20) the chamber pressure collapses. This causes the second spring (29) to reposition cone (28) thus closing channel (27). This ends the dispensing step, irrespective of how the pump head is further actuated and/or how the plunger/piston is retracted. The dose (volume) of the supplied substance is determined by the inner diameter dis of hollow body (15) and the distance covered by piston (17) before reaching the annular recess (20). [0054] Once the hollow stem (18) is released, first spring (24) will push piston (17) upwards along the hollow body (15). On its way up the elastic lower lip of piston (17) will exit the annular recess (20) and reengage with the inner diameter of the chamber (19) thus sealing said chamber. Further travel of piston (17) causes the chamber pressure to drop further. The reduced chamber pressure allows ball (21) to leave its conical seat, i.e. opens up the seal. The reduced chamber pressure draws fresh liquid or paste from the large reservoir into chamber (19) until the shoulder of stem (18) makes contact with bar (52). This contact of stem (18) and the bar (52) ends the cycle of operation.

[0055] Therefore, in one embodiment of the present invention, the pump dispenser for dispensing multiples of a predetermined base-dosage of a liquid or paste-like pharmaceutical comprises at least one pump head comprising a hollow body with a chamber of a defined inner volume and a defined inner diameter, wherein the hollow body further comprises a recess that has a diameter that is larger than said inner diameter of the chamber.

[0056] While this mechanism is given as one example of how a predetermined amount of fluid can be dispensed with a high degree of reproducibility, this mechanism is only meant to serve as an example of the overall principle. The person skilled in the art readily knows of other mechanisms working in the same or in a similar manner.

[0057] In one embodiment according to the present invention and in order to mitigate any potential (small) error in reproducibility in regard to the absolute volume dispensed (for example an error of a fraction of a millilitre), the overall dispensed volume per stroke (i.e. the volume of the predetermined base- dosage) is comparatively large, for example more thanθ.3 ml per stroke, more than 0.5 ml per stroke or more than 1 ml per stroke. As a consequence, in one embodiment according to the present invention, the volume as defined by the chamber inside the hollow body of the dispenser head is more than 0.3 ml, more than 0.5 ml or more than 1 ml.

[0058] In one embodiment according to the present invention, while the volume dispensed per stroke is comparatively high, the concentration of the active ingredient in said predetermined dispensed volume is comparatively low, for example lower than 50 % (by volume), lower than 10 % or lower than 5 % or lower than 1 %. For example, 5 mg of active ingredient may be present in a base-dosage of 0.5 ml (resulting in a 1 % solution).

[0059] By means of dispensing a comparatively large volume with a comparatively low concentration of active ingredient(s), any possible variation in dispensed volume per successive stroke translates only into a small variation in dispensed active ingredient, i.e. in base-dosage.

[0060] Commonly used droplet bottles for dispensing liquid pharmaceuticals comprise a particularly narrow opening or spout through which only small droplets can be expelled. Due to the geometric constraint of the small opening and the action of surface tension, the volume of these small droplets is comparatively constant, albeit very small. In order to compensate for volume fluctuations and in order to achieve a final volume that can be reasonably administered, for example in a spoon, a large number of these small droplets needs to be dispensed in order to arrive at the one pre- described dosage, for example 20 droplets or 30 droplets. This administration scheme has a couple of draw-backs, in particular the requirement to count a large number of droplets. Therefore, such an administration scheme is not suitable for patients that are physically and/or mentally impaired. By contrast, the presently described pump-dispenser is designed to have an easy-to-use actuation head (as known, for example, from everyday usage soap dispensers) while dispensing the required base-dosage in one stroke. For example in a titration scheme requiring the administration of multiples of a base-dosage, for example two and three times the base-dosage, this may be achieved in the comparatively small number of two or three strokes (using a droplet-based dispenser as described above, for example the dispensing of two or three times 20 droplets would be required to achieve the same result).

[0061] In one embodiment according to the present invention, the spout of the pump dispenser, i.e. the part of the pump head out of which the liquid, viscous or paste-like pharmaceutical is ultimately expelled is arcuate, i.e. has at least one portion that is substantially parallel in the horizontal direction and has at least one portion that is inclined in at least a 45 degree angle relative to the horizontal plane. This arcuate spout allows for a less spill-prone dispensing and is of particular advantage if the user of the dispenser is an older, handicapped or visually impaired patient.