CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of U.S. Provisional Application No.

62/589,326, filed on November 21, 2017, which is herein incorporated by reference in its entirety.

BACKGROUND

[0002] Depositing drug in the upper nasal cavity is difficult to accomplish due to the complex architecture of the nasal cavity and the turbinate guided air path for inhaled breath through the nose. These natural structures act to prevent materials from depositing in the upper nasal cavity as a way to protect this entry way into the central nervous system (CNS). Existing nasal drop or spray devices are designed to saturate the lower nasal cavity. Drug deposited on the lower nasal cavity is absorbed into the blood stream instead of the CNS, eliminating an advantage of using the nasal route for CNS delivery.

[0003] A more elegant approach to the intranasal delivery of compounds or mixtures is needed.

SUMMARY

[0004] A device for delivering a compound to the upper nasal cavity is described. In one embodiment, the device includes an actuator body and a tip configured to removably couple to the actuator body. The actuator body comprises a propellant channel that is configured to be in fluid communication with a canister containing a propellant. The tip comprises an outer wall and an inner wall, an exit channel, an inlet interface, one or more grooves, and an outlet orifice. The inner wall forms the exit channel which extends between a proximal end and a distal end of the tip. The inlet interface is positioned about a distal end of the outer wall, and the inlet interface is configured to couple to a compound container containing the compound. The one or more grooves are positioned about the inlet interface, where, when the compound container is coupled to the inlet interface, each groove is in fluid communication with the propellant channel and the exit channel. The outlet orifice is disposed at the distal end of the exit channel, such that propellant released from the canister travels through the propellant channel and the one or more grooves, into the compound container, thereby contacting the compound and propelling the compound through the exit channel and out the outlet orifice.

[0005] In one embodiment, the one or more grooves are oriented on the inlet interface such that the one or more grooves are configured to direct propellant released from the canister into the compound container in an orthogonal or near-orthogonal direction relative to a bottom surface of the compound container, thereby agitating and entraining the compound in the compound container with the released propellant.

[0006] This configuration enables a user to load and unload a compound container onto the tip for administration of the compound.

[0007] The invention will best be understood by reference to the following detailed description of various embodiments, taken in conjunction with any accompanying drawings. The discussion below is descriptive, illustrative and exemplary and is not to be taken as limiting the scope defined by any appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0001] Figure (FIG.) 1 is an intranasal drug delivery device, in accordance with one or more embodiments.

[0002] FIG. 2 illustrates a partial cross-sectional view of the device, in accordance with one or more embodiments.

[0003] FIG. 3 is a perspective view of a tip and a capsule, in accordance with one or more embodiments.

[0004] FIG. 4 is cross-sectional view of the tip and the capsule coupled to the device, in accordance with one or more embodiments.

[0005] FIG. 5 is an exploded view of the tip and the capsule, in accordance with one or more embodiments.

[0006] FIG. 6 is a perspective view of the tip with the capsule attached, in accordance with one or more embodiments

[0007] FIG. 7 is a cross-sectional view of the tip with the capsule attached, in accordance with one or more embodiments.

[0008] FIG. 8 is a cross-sectional view of the tip, in accordance with one or more embodiments.

[0009] FIG. 9 is a cross-sectional view of the tip, in accordance with one or more embodiments.

[0010] FIG. 10 is cross-sectional view of an inlet interface of the tip with the capsule attached, in accordance with one or more embodiments.

[0011] FIG. 11A-11D are cross-sectional views of a tip of the device, in accordance with one or more embodiments. [0012] FIG. 12 is a perspective view of the tip, in accordance with one or more embodiments.

[0013] FIG. 13 is a perspective view of the tip, in accordance with one or more embodiments.

[0014] FIG. 14 is perspective view of the tip coupled to the device, in accordance with one or more embodiments.

[0015] FIG. 15 is a cross-sectional view of the tip coupled to the device, in accordance with one or more embodiments.

[0016] FIG. 16 is a zoomed-in view of the inlet interface with the capsule attached, in accordance with one or more embodiments.

[0017] FIG. 17 is a perspective view of a second embodiment of a tip, in accordance with one or more embodiments.

[0018] FIG. 18 is a perspective view of the tip of FIG. 17 with a capsule attached, in accordance with one or more embodiments.

[0019] FIG. 19 is a perspective view of a puncture member, in accordance with one or more embodiments.

[0020] FIG. 20 is a perspective view of the puncture member, in accordance with one or more embodiments.

[0021] FIG. 21 illustrates a flow path of the second embodiment of the device, in accordance with one or more embodiments.

[0022] The figures depict embodiments of the present disclosure for purposes of illustration only. One skilled in the art will readily recognize from the following description that alternative embodiments of the structures and methods illustrated herein may be employed without departing from the principles, or benefits touted, of the disclosure described herein.

DETAILED DESCRIPTION

[0023] Unless stated otherwise, the following terms and phrases as used herein are intended to have the following meanings:

[0024] When trade names are used herein, applicants intend to independently include the trade name product formulation, the generic drug, and the active pharmaceutical ingredient(s) of the trade name product. [0025] For clarity of disclosure, and not by way of limitation, the detailed description of the invention is divided into the subsections which follow.

[0026] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art pertinent to the methods and compositions described. The following references provide one of skill with a non-exclusive guide to a general definition of many of the terms used herein: Hale & Margham, The Harper Collins Dictionary of Biology (Harper Perennial, New York, N.Y., 1991); King & Stansfield, A Dictionary of Genetics (Oxford University Press, 4th ed. 1990); Hawley’s Condensed Chemical Dictionary (John Wiley & Sons, l3th ed. 1997); and Stedmans’ Medical Dictionary (Uippincott Williams & Wilkins, 27th ed. 2000). As used herein, the following terms and phrases have the meanings ascribed to them unless specified otherwise.

[0027] As shown in FIGS. 1 and 2, the intranasal device 100 is designed to deliver a consistent mass of compound into the nasal cavity. For example, but not limited to, the compound may be an intranasal formulation in a powder form. The device 100 targets a specific region of the nasal cavity utilizing a narrow, targeted delivery plume. Specifically, the device 100 provides the compound to the upper one third of the nasal cavity. In one embodiment, the device 100 is used to administer the compound into the upper nasal cavity of a human. The upper nasal cavity includes the olfactory region and the middle and upper turbinate regions. In another embodiment, the device 100 is used to administer the compound into the upper nasal cavity of a non-human primate. The device 100 is also designed to simplify clinician loading of the compound into the device 100 and use thereof. The device 100 may be re-used to administer several doses of the compound.

[0028] FIG. 2 illustrates a partial cross-sectional view of the device 100 for delivering a compound intranasally. In the embodiment of FIG. 2, the device 100 includes an actuator body 105, a propellant canister 110, and a tip 115. The tip 115 includes an outer wall 205 and an inner wall 210, an exit channel 215, an inlet interface 220, one or more grooves 305 (shown in FIG. 3), an outlet orifice 225, and a nozzle 230. FIG. 2 illustrates the compound container 235 coupled to the inlet interface 220. The compound contained in the compound container 235 may be a liquid or a powder. In the embodiment of FIG. 2, the compound is a powder.

[0029] As shown in FIG. 2, the device 100 includes a propellant canister 110 positioned within the actuator body 105. The propellant canister 110 contains propellant. In one embodiment, the propellant may be pressurized. The propellant is a fluid, for example, a liquid or gas. In one aspect, the propellant is a liquid. In another aspect, the propellant is a gas. Propellants include pharmaceutically suitable propellants. Some examples of pharmaceutically suitable propellants include hydrofluoroalkane (HFA) including but not limited to HFA, HFA 227, HFA l34a, HFA-FP, HFA-BP and the like HFA's. In one aspect, the propellant is liquid HFA. In another aspect, the propellant is gaseous HFA. Additional examples of suitable propellants include nitrogen or chloroflourocarbons (CFC).

Additionally, propellants may be pressurized air (e.g. ambient air). The canister 110 may be a metered dose inhaler (MDI) device that includes a pressurized canister and metering valve 240 (including stem) to meter the propellant upon actuation. In one embodiment, a pump fitment (not shown) secures the metered valve 240 to the canister 110 and holds both components in place during device 100 use. One series of embodiments of the pump fitment consists of securing interfaces that retain the pump fitment within the actuator body 105, provide vertical displacement, and prevent rotation during installation of the canister 110.

[0030] The propellant canister 110 may have a capacity for distributing propellant for a certain number of doses. In one embodiment, the device 100 may be shipped without a canister 110 and the canister 110 may be loaded into the actuator body 105 by the user. In some embodiments, the propellant canister may be replaced with a new propellant canister, such that the device 100 may be reused. In one aspect, when the MDI device is actuated, a discrete amount of pressurized HFA fluid is released. The MDI may contain between about 30 to about 300 actuations, inclusive of endpoints, of HFA propellant. The amount of fluid propellant released upon actuation may be between about 20 mΐ and about 200 mΐ inclusive of endpoints, of liquid propellant.

[0031] The actuator body 105 comprises a propellant channel 245 that is in fluid communication with the propellant canister 110. The propellant channel 245 is in fluid communication with the inlet interface 220, which is configured to couple to the compound container 235 such that propellant released from the propellant canister 110 can be introduced into the compound container 235 via the one or more grooves 305 on the inlet interface 220. In the embodiment of FIG. 2, the propellant channel 245 includes a port 250 at a distal end for receiving the tip 115. In this configuration, the tip 115 may be coupled and decoupled to the actuator body 105 by inserting the tip 115 into the port 250. In other embodiments, the port 250 may be inserted into the tip 115. In some embodiments, the port 250 and/or the tip 115 may include a sealing interface that creates an airtight seal between the propellant channel 245 and the tip 115 such that propellant released from the canister 110 does not escape out of the propellant channel 245 and is directed to the inlet interface 220.

[0032] The tip 115 may be coupled and decoupled to the actuator body 105, which enables a user to load and unload a compound container 235 to and from the inlet interface 220. The tip 115 includes the outer wall 205 and the inner wall 210, where the inner wall forms the exit channel 215 which extends between a proximal end and a distal end of the tip 115. The inlet interface 220 is positioned about a distal end of the outer wall 205, and the inlet interface 220 couples the compound container 235. In the embodiment of FIG. 2, the inlet interface 220 is a collar that may be inserted into the compound container 235. In other embodiments, the inlet interface 220 may be a ring, band, port, or strap that interfaces with the compound container 235. The inlet interface 220 includes one or more grooves 305 (shown in FIG. 3) for directing propellant released from the canister 110 into the compound container 235 coupled to the inlet interface 220. The released propellant then contacts the compound within the compound container 235, agitating and entraining the compound and propelling the compound through the exit channel 215 and out the outlet orifice 225 located at a distal end of the exit channel 215. In the embodiment of FIG. 2, the tip 115 includes a nozzle at the distal end of the exit channel 215 for directing the released propellant and the compound out of the outlet orifice in a narrow plume.

[0033] FIG. 3 is a perspective view of the tip 1 15 and a compound container, in accordance with one or more embodiments. In the embodiment of FIG. 3, the compound container 235 is a capsule. The capsule may be comprised of two portions fitted together. When separated, a portion of the capsule (e.g., a half-capsule, as shown in FIGS. 5-7) may be coupled to the tip 115. In use, the compound container 235 may contain a compound within the capsule. In one example, the compound is a powder. As shown in FIG. 5, the half- capsule comprises an exit opening 505 of the compound container 235. The exit opening 505 may be coupled to the inlet interface 220, as shown in FIGS. 6-7. In the embodiments of FIGS. 6-7, the inlet interface 220 is inserted into the exit opening 505, and the compound container 235 may be secured to the inlet interface 220 via an interference fit. In an alternate embodiment, the exit opening 505 may be inserted into the inlet interface 220. As shown in FIGS. 7-8, the tip 115 has the outer wall 205 and the inner wall 210, where the exit channel 215 is formed by a bore or lumen through the inner wall 210. The exit opening 505 is fitted about the inlet interface 220 such that the compound container 235 and the exit channel 215 are in fluid communication. [0034] As shown in FIGS. 6, 7, and 10, the inlet interface 220 is, for example, a ring, band, port, collar, or strap interfacing with the compound container 235. As shown in FIGS. 3, 5, 6, 11A-11D, 12, and 13, one or more grooves 305 are positioned on the inlet interface 220 and create a flow path for the propellant released from the propellant canister 110 to travel into the compound container 235. An example of the grooves 305 includes but is not limited to channels, slots, radial ports, or passageways. The grooves 305 provide a pathway via the inlet interface 220 by which the propellant flows into the compound container 235. In one example, there are a plurality of grooves 305. The grooves 305 may be equally spaced about the inlet interface 220. The grooves 305 may be of equal size to each other or may be of differing sizes. The grooves 305 run along a length of the inlet interface 220 such that, when the compound container 235 is coupled to the inlet interface 220, a first portion of each groove 305 is exposed within the propellant channel 245 and a second portion of each groove 305 is positioned within the compound container 235. As shown in FIG. 3, the inlet interface 220 includes a ledge 310 that is designed to abut the compound container 235 when coupled to the inlet interface 220 and the grooves 305 extend past the ledge 310 such that the grooves 305 are not fully covered by the compound container 235.

[0035] In use, as shown by the direction of the arrows in FIG. 4, the propellant released from the canister 110 flows through the propellant channel 245 and into the compound container 235 via the grooves 305. The exit channel 215 is aligned with the exit opening 505 of the compound container 235. The propellant flows in the grooves 305 of the inlet interface 220, into the compound container 235 to agitate the powder, and the powder and the propellant exit the compound container 235 via the exit opening 505 congruent with the exit channel 215. The propellant and powder mixture are carried through the exit channel 215 through the nozzle 230 and exit the device 100 at the outlet orifice 225. In one example, the tip 115 may have one or a plurality of outlet orifices. The plume exiting the outlet orifice 225 has a narrow spray plume.

[0036] In one example of use of the device 100, at time of use, a user separates a pre- filled capsule into its two halves. In one example, the capsule is prefilled with a powder compound. The half-capsule is coupled to the tip 115 via the inlet interface 220. As shown in FIGS. 13 and 14, the tip 115 is then coupled to the actuator body 105. A propelling gas, for example from either a refrigerant or compressed gas source, is directed through the propellant channel 245 and towards the filled powder capsule. The grooves 305 around the inlet interface 220 of the tip 115 introduce high velocity jets of propellant gas which agitate the dry powder into a suspension within the propellant gas (data not shown but confirmed with high speed close up video). Grooves 305 that introduce gas tangentially to the semispherical-shaped bottom of the compound container 235 creates jets which enhance stirring and entrainment of powder. Once the powder has been suspended, it is evacuated through the exit opening 505, into the exit channel 215, and out the outlet orifice 225 of the device 100.

[0037] Generally, when accelerating a powder formulation through a restricting orifice, any constricting junction will cause the powder to clog. Since the powder administered by this device 100 is suspended within the propellant gas prior to evacuation, it can be further throttled and directed without device clogging. As a result, a much larger mass of powder can be delivered through a much smaller outlet orifice without the device 100 being prohibitively long. The time from propellant actuation to end of compound delivery is less than 1 second.

[0038] The grooves 305 in the proximal end of the tip 115 promote gas flow into the compound container 235. In one example, the HFA gas is directed (e.g. orthogonally or near- orthogonally) at the surface of the powder dose residing in the compound container 235, which creates rapid agitation and entrainment of the powder. The semispherical shape of the compound container 235 promotes gas redirection to the exit channel 215 of the tip 115 as shown in FIG. 4. The arrows of FIGS. 2 and 4 show the direction of propellant flow after the device 100 has been actuated.

[0039] The actuator body 105 attached and seals to the propellant canister 110 and the tip 115, creating a pressurized flow path for the propellant gas. In certain aspects, the actuator body 105 is a reusable component. In certain aspects, the canister 110 is a reusable component.

[0040] In one example, the compound container 235 is a standard Size 3 drug capsule, although one of skill in the art would know how to use other sized drug capsules and modify the device 100 to fit same. Additionally, in another example, the compound container 235 may not be a capsule, but another container capable of containing a compound, such as but not limited to an ampoule. In one example, the ampoule may be made of plastic, and in one example it may be a blow fill sealed ampoule. To load the device 100, the user or clinician will separate a prefilled formulation containing capsule, discard the cap, and install the capsule over the tip 115. An empty compound container 235 can also be filled by a clinician at time of use before installing the compound container 235 onto the tip 115. In certain examples, the capsule is a disposable component.

[0041] The tip 115 receives the compound container 235 during loading and is then coupled to the actuator body 105 prior to use. When the propellant canister 110 is actuated, expanding propellant gas is introduced into the compound container 235 via the grooves 305 around the inlet interface 220 of the tip 115. The resulting propellant gas jets agitate and entrain the powder formulation within the compound container 235, which then exits through the exit channel 215 and the outlet orifice 225 of the tip 115. In one example, the tip 115 is a disposable component. FIG. 11A illustrates example measurements of the tip 115 with units in inches. In the embodiment of FIG. 11D, the inlet interface 220 may include a radius along a bottom edge 222 to aid placement of the compound container 235 onto the tip 115. The radius of curvature may range between approximately 0.005 inches to 0.025 inches, inclusive.

[0042] FIGS. 17-18 illustrate perspective views of a second embodiment of a tip 1700. Similar to the tip 115, the tip 1700 may be coupled and decoupled to the actuator body 105, which enables a user to load and unload a compound container 1705 to and from the tip 1700 for delivery to an upper nasal cavity of a user using the device 100. As shown in FIGS. 17- 18, a compound container 1705 is a capsule. The compound container 1705 may, in one example, contain a powder. In the embodiments of FIGS. 17-18, the tip 1700 includes an inlet interface 1710 for coupling the compound container 1705, where the inlet interface 1710 has a puncture member 1715. The puncture member 1715 is designed to puncture the compound container 1705 to create an opening in the compound container 1705. The puncture member 1715 may comprise a sharp point, a sharp angle, a blade-like edge, or other suitable geometries for puncturing the compound container 1705. In one embodiment, the inlet interface 1710 includes more than one puncture member 1715, where each puncture member 1715 is designed to puncture the compound container 1705. The puncture members 1715 may be positioned about the inlet interface 1710 in a pattern, symmetrically, or at random. In one example, in use, a user may remove the tip 1700 from the actuator body 105, load the compound container 1705 into the port 250 of the propellant channel 245, and then insert the tip 1700 back into the port 250. As the tip 1700 is coupled to the actuator body 105, the puncture member 1715 punctures the capsule. In this configuration, the punctured capsule fits around the puncture member 1715, as shown in FIG. 18. In alternate

embodiments, the puncture member 1900 may comprise a plurality of puncture points 1905 that each puncture the compound container 1705. The plurality of puncture points 1905 may be spaced about the puncture member 1900, or each

[0043] FIGS. 19-20 illustrate perspective views of a puncture member 1900 that may be used with the tip 1700, in accordance with one or more embodiments. As shown in FIG. 19, the puncture member 1900 may be a collar, ring, band, port or strap that couples with the punctured compound container 1705. The puncture member 1900 includes one or more puncture grooves 1910 that, similar to grooves 305, form a flow path between the propellant channel 245 and the compound container 1705. The propellant from the propellant canister 110 enters via the one or more puncture grooves 1910 of puncture member 1900 and flows along the puncture grooves 1910 and into the punctured compound container 1705. As shown in FIGS. 19-20, the puncture member 1900 includes a plurality of puncture openings 1915. In the embodiments of FIGS. 19-21, the puncture openings 1915 are in fluid communication with the exit channel 215. The propellant from the propellant canister 110 flows into the puncture grooves 1910, mixes with the powder in the punctured compound container 1705, and flows into the puncture openings 1905 to the exit channel 215. The arrows of FIG. 21 illustrate the flow path of the propellant. The exit channel 215 provides a route for the propellant and the powder to the nozzle 230 and the outlet orifice 225. The mixture of propellant and powder exit the device 100 via the outlet orifice 225. The plume exiting the device 100 is a narrow spray plume. In this embodiment, the puncture member 1900 may be integrally molded as a single piece or may consist of two or more pieces. In one example, the puncture member 1900 may be a separately molded piece acting in association with the inlet interface 1710 (where the capsule attaches). In some embodiments, an inlet interface may include more than one puncture member 1900.

[0044] As shown in FIGS. 19 and 20, as an alternate to the capsule being manually separated prior to placement on the tip 1700, the tip 1700 may include an integrated puncture member 1900 and puncture grooves 1910. In order to create a repeatable puncture of the compound container 1705, a puncture member 1900 comes to a single point, puncture point 1905. In one example, the puncture point 1905 includes puncture openings 1910 that are radially spaced about the puncture point 1905. The puncture openings 1910 are in fluid communication with the exit channel 215 for the powder to be evacuated from the compound container 1705.

[0045] As shown in FIG. 21, by allowing the propellant flow path to be created with an inline puncture motion, loading the compound container 1705 onto the tip 1700 is simplified for the user, as the compound container 1705 does not require manual manipulation and separation. In one example, the puncture member 1900 is formed integrally with the tip 1700. In one example, the filled compound container 1705 may be filled and installed into either the actuator body 105 or the tip 1700 during manufacturing of the device 100. At time of use, a user may apply a linear motion to drive the puncture member 1900 into the pre-filled compound container 1705, creating a complete gas flow path for dosing prior to propellant actuation.

[0046] The invention is further described in the following examples, which are not intended to limit the scope of the invention.

Example 1

Powder capsule

[0047] In one embodiment, a device was constructed and tested. Testing was conducted for residual powder in the compound container after actuation. The device has equivalent performance of powder delivery, as determined by residuals after actuation, when 2 or more but less than 6 grooves on the inlet interface are used. In this example, the grooves are in combination with 63mg of HFA propellant and a .040” outlet orifice of the nozzle. Four grooves (every 90 degrees) were found to provide uniform gas delivery.

Dose mass

[0048] Dose mass reproducibility testing was conducted. The standard deviation on dose delivery shows the device is capable of delivering consistent dose masses. The mean residual of dose left in the device was <5%, showing very little dose is lost in the device.

Table 1 : Mass reproducibility of final molded device, Values in milligrams Additional Configuration Tnformation

[0049] The foregoing description of the embodiments of the disclosure has been presented for the purpose of illustration; it is not intended to be exhaustive or to limit the disclosure to the precise forms disclosed. Persons skilled in the relevant art can appreciate that many modifications and variations are possible in light of the above disclosure.

[0050] The language used in the specification has been principally selected for readability and instructional purposes, and it may not have been selected to delineate or circumscribe the inventive subject matter. It is therefore intended that the scope of the disclosure be limited not by this detailed description, but rather by any claims that issue on an application based hereon. Accordingly, the disclosure of the embodiments is intended to be illustrative, but not limiting, of the scope of the disclosure, which is set forth in the following claims.