Controllable rate turbulating nozzle

Abstract

A piercing device for use in internally pierced blister delivery devices include a base, a piercer body and an internal fluid path. The internal fluid path includes one or more inlet channels into a central cavity which is connected to one or more delivery channels and exit ports. The cavity is defined by angular walls and top to create turbulence in the fluid flow and to produce a controllable spray, mist, drops, plume or stream delivery. The piercer body also provides a pointed lancet disposed in the center of the exit ports for piercing the lidstock of a formed blister.

Claims

1. A piercing device for delivering a predetermined quantity of a flowable liquid or powder contained in a crushable blister into a spray, plume, stream or droplets, said device comprising: a base comprising a top; a substantially hollow, elongated member extending from the base and comprising a body region and terminating in a lancet piercing tip region; the lancet piercing tip region comprising a tip and a base end; an internal delivery channel formed by the hollow interior of the elongated member extending from the base and terminating in a plurality of discharge ports arranged around the base end of piercing tip region; wherein the internal delivery channel comprises: a central cavity; and a plurality of outlet channels radially disposed around the central cavity and open to the central cavity along at least a portion of an innermost side of each outlet channel and wherein each outlet channel terminates in one of the plurality of discharge ports, wherein the central cavity is defined by angular walls disposed between the outlet channels and an angular top surface proximate the tip configured to deflect fluid from the central cavity into the outlet channels when the fluid enters one or more conduits under pressure; one or more inlet ports in the base in fluid communication with an interior of the crushable blister, and the one or more conduits providing fluid communication between the one or more inlet ports and the internal delivery channel.

2. The piercing device of claim 1, wherein at least one of the conduits from an inlet port to the internal delivery channel comprises one or more bends or turns.

3. The piercing device of claim 2, wherein one or more of the bends or turns is an angle of from 20 to 135.

4. The piercing device of claim 2, wherein at least one of the conduits from an inlet port to the internal delivery channel comprises one or more 90 turns.

5. The piercing device of claim 1, wherein the internal delivery channel comprises three outlet channels disposed radially around the central cavity and each terminating in one of three discharge ports disposed radially around the base end of the piercing tip region.

6. The piercing device of claim 1, wherein the piercing tip region is configured as a three sided pyramid.

7. The piercing device of claim 1, wherein during use, delivery of a fluid that enters said one or more inlet ports under pressure, creates a laminar flow as the fluid flows through the one or more conduits and creates a turbulent flow as the fluid flows into and through the internal delivery channel and one or more of said plurality of outlet channels, such that the fluid is released through the discharge ports as a spray or mist.

8. A dosage form containing the piercing device of claim 1 and a liquid or powder composition.

9. The dosage form of claim 8, wherein the liquid or powder composition is a medical composition.

10. The dosage form of claim 9, wherein the liquid or powder composition is a medical composition for administration to the eye, ear, nasal passage or topical area of a user.

11. The dosage form of claim 9, wherein the liquid or powder composition is a medical composition for administration to the eye of a user.

12. The dosage form of claim 8, wherein the dosage form contains a volume of from 1 l to 50 l of flowable liquid or powder.

13. The dosage form of claim 8, wherein the dosage form contains a volume of from 75 l to 500 l of flowable liquid or powder.

14. The dosage form of claim 8, wherein the dosage form contains a volume of from 1 l to 1000 l of flowable liquid or powder.

15. The dosage form of claim 8, wherein the outlet channels and discharge ports have a bilobal cross section.

16. An internally pierced dosage form comprising: a modified dome shaped blister with a circular base; a planar sheet of pierceable material sealed to the base of the blister; and an internal chamber contained within the blister and the planar sheet; a piercing device and a medical composition contained in the internal chamber; and wherein the piercing device comprises: a base comprising a top; a substantially hollow, elongated member extending from the base and comprising a body region and terminating in a lancet piercing tip region; wherein the lancet piercing tip region comprises a base end; an internal delivery channel formed by the hollow interior of the elongated member extending from the base and terminating in a plurality of discharge ports arranged around the base end of the piercing tip region; one or more inlet ports in the base in fluid communication with the interior of the crushable blister; and one or more conduits providing fluid communication between the one or more inlet ports and the internal delivery channel.

17. The internally pierced dosage form of claim 16, wherein the internal delivery channel comprises: a central cavity extending from, and in fluid communication with the one or more conduits, and a plurality of outlet channels radially disposed around the central cavity and open to the central cavity along at least a portion of an innermost side of each outlet channel and wherein each outlet channel terminates in one of said plurality of discharge ports, wherein the central cavity is defined by angular walls disposed between the outlet channels and an angular top surface proximate the lancet piercing tip region configured to deflect a fluid from the central cavity into the outlet channels when the fluid enters the internal delivery channel under pressure.

18. The internally pierced dosage form of claim 16, wherein at least one of the conduits from an inlet port to the internal delivery channel comprises one or more bends or turns.

19. The internally pierced dosage form of claim 18, wherein one or more of the bends or turns is an angle of from 20 to 135.

20. The internally pierced dosage form of claim 18, wherein at least one of the conduits from an inlet port to the internal delivery channel comprises one or more 90 turns.

21. The internally pierced dosage form of claim 16, comprising three outlet channels disposed radially around the central cavity and each terminating in one of three discharge ports disposed radially around the base end of the piercing tip region.

22. The internally pierced dosage form of claim 16, wherein the piercing tip region is configured as a three sided pyramid.

23. The internally pierced dosage form of claim 17, wherein during use, delivery of a fluid that enters said one or more inlet ports under pressure, creates a laminar flow as a fluid flows through the one or more conduits and creates a turbulent flow as the fluid flows into and through the internal delivery channel and outlet channels, such that the fluid is released through the discharge ports as a spray or mist.

24. The internally pierced dosage form of claim 16, wherein the medical composition is a fluid composition for administration to the eye, ear, nasal passage or topical area of a user.

25. The internally pierced dosage form of claim 16, wherein the medical composition is a fluid composition for administration to the eye of a user.

26. The internally pierced dosage form of claim 16, wherein the dosage form contains a volume of from 1 l to 50 l of flowable liquid or powder.

27. The internally pierced dosage form of claim 16, wherein the dosage form contains a volume of from 75 l to 500 l of flowable liquid or powder.

28. The internally pierced dosage form of claim 16, wherein the dosage form contains a volume of from 1 l to 1000 l of flowable liquid or powder.

29. The internally pierced dosage form of claim 17, wherein the outlet channels and discharge ports have a bilobal cross section.

30. A piercing device for delivering a predetermined quantity of a flowable liquid or powder contained in a crushable blister into a spray, plume, stream or droplets, said device comprising: a base comprising a top and one or more inlet ports in fluid communication with the interior of the crushable blister; a substantially hollow, elongated member extending from the base and comprising a body region and terminating in a lancet piercing tip region, wherein the lancet piercing tip region comprises a base end; an internal delivery channel formed by the hollow interior of the elongated member extending from the base and terminating in a plurality of bilobal discharge ports arranged around the base end of the lancet piercing tip region, said internal delivery channel comprising a central cavity extending from, and in fluid communication with one or more inlet ports, and a plurality of bilobal shaped outlet channels radially disposed around the central cavity and open to the central cavity along at least a portion of an innermost side of each outlet channel and each outlet channel terminating in one of said bilobal discharge ports, wherein the central cavity is defined by angular walls disposed between the outlet channels and an angular top surface proximate the piercing tip region configured to deflect fluid from the central cavity into the outlet channels when the fluid enters the inlet ports under pressure; and one or more conduits providing fluid communication between the one or more inlet ports and the internal delivery channel.

31. A piercing device for delivering a predetermined quantity of a flowable liquid or powder contained in a crushable blister into a spray, plume, stream or droplets, said device comprising: a base comprising a top and one or more inlet ports in fluid communication with an interior of the crushable blister and each of said one or more inlet ports in fluid communication with an internal delivery channel through a conduit; a substantially hollow, elongated member extending from the base and comprising a body region and terminating in a lancet piercing tip region configured as a three sided pyramid; and the lancet piercing tip region comprising a base end; wherein the internal delivery channel is formed by the hollow interior of the elongated member, said internal delivery channel comprising a central cavity extending from the base and three outlet channels having bilobal cross sections radially disposed around the central cavity and open to the central cavity along at least a portion of an innermost side of each outlet channel and each outlet channel terminating in one of said three discharge ports each having a bilobal cross section and radially disposed around the base end of the lancet piercing tip region, wherein the central cavity is defined by angular walls disposed between the outlet channels and an angular top surface proximate the lancet piercing tip region configured to deflect fluid from the central cavity into the outlet channels when the fluid enters the one or more inlet ports under pressure.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present invention. The invention may be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein.

(2) FIG. 1 is a side view of an embodiment of a lancet tipped piercer.

(3) FIG. 2 is a side view of the piercer shown in FIG. 1 rotated 120 about the center of the lancet.

(4) FIG. 3 is a perspective top view of the piercer shown in FIG. 1.

(5) FIG. 4 is top plan view of the piercer shown in FIG. 1.

(6) FIG. 5 is a bottom plan view of the bottom of the base top of the piercer shown in FIG. 1.

(7) FIG. 6 is a sectional view of a piercer as shown in FIG. 1.

(8) FIG. 7 is an alternate sectional view of a piercer as shown in FIG. 1.

(9) FIG. 8 is a sectional view through the body of the piercer as shown in FIG. 1.

(10) FIG. 9 is a sectional view through the piercing region of a piercer as shown in FIG. 1.

(11) FIG. 10 is a horizontal section view through a base of a piercer as shown in FIG. 1.

DETAILED DESCRIPTION

(12) Preferred embodiments of the present disclosure are directed to dosage forms that contain a measured dose of one or more pharmaceutically active agents and a piercable section such that the dosage form can be pierced to release the contents under pressure. When using the term under pressure in the disclosure, it is understood that the pressure is typically an externally applied pressure rather than internal pressure within the dosage form itself. In typical operation, a plunger, lever, ram, wheel, or some other mechanical device contacts the dosage form with sufficient force to crush the dosage form against a piercing member and force the contents out of the opening. The dosage form can be generated using methods well known to those of skill in the art, including, for example, form fill seal technology or blow fill seal technology, or by deep draw forming as described in U.S. Application Publication No. 2009/0071108, incorporated herein in its entirety by reference.

(13) The form-fill-seal process can be used to create a blister, for example a blister pack, from rolls of flat sheet or film, inserted with a piercing mechanism, filled with the pharmaceutically active agent, and closed or sealed on the same equipment. This process involves a formed base which has the cavity in which the pharmaceutically active agent, or an agent that may be mixed or combined with a pharmaceutically active agent, is placed, and a lidding, for example of foil, through which the agent is dispensed out of the blister. Blow fill seal technology involves forming, filling, and sealing a dosage form in a continuous process in a sterile enclosed area inside a machine.

(14) The film layer may include a variety of different materials, including, but not limited to, thermoplastics, polymers, copolymers, composites and laminates. When the unit dose is a pharmaceutical dosage form, the film will need to be able to undergo aseptic manufacturing processes to produce sterile shaped articles, for example gamma ray irradiation. Preferably the film is flexible but capable of holding its shape, can be crushed with minimal force, creates a barrier, withstands radiation, and has desirable chemical properties (e.g., does not react with the pharmaceutical dosage form to be administered). For blister packs, the film is preferably a foil laminate, and more preferably a metal-plastic laminate. The metal-plastic laminate comprises a metal foil coated on at least one side, or on both sides, with a plastic layer. If the metal-plastic laminate comprises a plastic layer on both sides of the metal foil, the plastic layers may be the same type of plastic layer, or different types of plastic layers.

(15) Materials which may be used in the plastic layer of the laminate are well known by those skilled in the art and include, but are not limited to, a variety of commercially available polymers and copolymers, such as polyvinylchloride, nylon, nylon derivatives, polybutylene terephthalate, polyethylene terephthalate, polyethylene, polypropylene, polystyrene, polyacetal, vinylidene chloride, propylene ethylene copolymers, polyethylene napthalate, fluoropolymers, cyclic polyolefins, polyamides, and similar materials or combinations thereof. The plastic layer may be present in the laminate at a thickness of about 8 m to about 80 m, about 10 m to about 70 m, about 15 m to about 60 m, about 20 m to about 50 m, or about 25 m to about 40 m, and any ranges therein. The plastic components may be non-stretched, or alternatively uniaxially or biaxially stretched, or may be thermoplastics such as halogen-containing polymers, polyolefins, polyamides, polyesters, acrylonitrile copolymers, or polyvinylchlorides. Typical examples of thermoplastics of the polyolefin type are polyethylenes such as low density polyethylene (LDPE), medium density polyethylene (MDPE), high density polyethylene (HDPE), uniaxially, or biaxially stretched polypropylenes, polypropylenes such as cast polypropylene and uniaxially or biaxially stretched polyethylene terephthalate (PET) from the polyester series. The above examples are in no way meant to be limiting, as other materials known in the art may be used in the plastic layer as well.

(16) Examples of plastics based on halogen-containing polymers include but are not limited to polymers of vinylchloride (PVC) and vinyl plastics, containing vinylchloride units in their structure, such as copolymers of vinylchloride and vinylesters of aliphatic acids, copolymers of vinylchloride and esters of acrylic or methacrylic acids or acrylonitrile, copolymers of diene compounds and unsaturated dicarboxyl acids or their anhydrides, copolymers of vinylchloride and vinylchloride with unsaturated aldehydes, ketones, etc., or polymers and copolymers of vinylidenchloride with vinylchloride or other polymerizable compounds. The vinyl-based thermoplastics may also be made soft or pliable in a conventional manner by means of primary or secondary softeners.

(17) If the plastic films comprise polyesters (PET-films), examples of polyesters include but are not limited to polyalkylene-terephthalate or polyalkylene-isophthalate with alkylene groups or radicals with 2 to 10 carbon atoms or alkylene groups with 2 to 10 carbon atoms interrupted by at least one oxygen atom, such as, e.g., polyethylene-terephthalate, polypropylene-terephthalate, polybutylene-terephthalate (polytetramethylene-terephthalate), polydecamethylene-terephthalate, poly 1,4-cyclohexyldimethylol-terephthalate or polyethylene-2,6-naphthalene-dicarboxylate or mixed polymers of polyalkylene-terephthalate and polyalkylene-isophthalate, where the fraction of isophthalate amount, e.g., to 1 to 10 mol. %, mixed polymers and terpolymers, also block polymers and grafted modifications of the above mentioned materials. Other useful polyesters are known in the field by the abbreviation PEN. Other polyesters are copolymers of terephthalic acid, a polycarboxyl acid with at least one glycol, copolymers of terephthalic acid, ethyleneglycol and an additional glycol, polyalkylene-terephthalates with alkylene groups or radicals with 2 to 10 carbon atoms, polyalkylene-terephthalates with alkylene groups or radicals with 2 to 10 carbon atoms which are interrupted by one or two oxygen atoms, polyalkylene-terephthalates with alkylene groups or radicals with 2 to 4 carbon atoms, and polyethyleneterephthalates (e.g., A-PET, PETP, PETG, G-PET). Glycol-modified polyesters are also referred to as PETG.

(18) Examples of polyolefins for plastic films include but are not limited to polyethylenes (PE), e.g., high density polyethylene (HDPE, density larger than 0.944 g/cm), medium density polyethylene (MDPE, density 0.926-0.940 g/cm), linear polyethylene of medium density (LMDPE, density 0.926.0.940 g/cm), low density polyethylene (LDPE, density 0.910-0.925 g/cm), and linear low density polyethylene (LLDPE, density 0.916-0.925 g/cm), for example as non oriented (PE film) or uniaxially or biaxially oriented films (oPE film), polypropylenes (PP), such as axially or biaxially oriented polypropylene (oPP film), or cast polypropylene (cPP film), amorphous or crystalline polypropylene or mixtures thereof, ataktic or isotaktic polypropylene or mixtures thereof, poly-1-butene, poly-3-methylbutene, poly-4-methylpententene and copolymers thereof, polyethylene with vinylacetate, vinylalcohol, acrylic acid, such as, e.g., ionomeric resins, such as copolymers of ethylene with 11% acrylic acid, methacrylic acid, acrylic esters, tetrafluorethylene or polypropylene, statistical copolymers, block polymers or olefin polymer-elastomer mixtures, ionomers, and ethylene-acrylic acid copolymers (EAA).

(19) If the plastic films comprise polyamide films (PA), examples of polyamides include but are not limited to polyamide 6, a homo-polymer of []-caprolactam (polycaprolactam); polyamide 11, polyamide 12, a homo-polymer of [o]-laurinlactam (polylaurinlactam); polyamide 6,6, a homo-polycondensate of hexamethylenediamine and adipinic acid (polyhexa-methylene-adi-amide); polyamide 6,10, a homo-polycondensate of hexa-methylene-diamine and sebacinic acid (poly-hexa-methylene-sebacamide); polyamide 6,12, a homo-polycondensate of hexa-methylene-diamine and dodecandic acid (poly-hexa-methylene-dodecanamide) or polyamide 6-3-T, a homo-polycondensate of trimethyl-hexa-methylene-diamine and terephthalic acid (poly-trimethyl-hexa-methylene-terephthalic-amide), and mixtures thereof.

(20) If the plastic comprise acrylnitrile-copolymers, examples of acrylnitrile-copolymers include but are not limited to copolymers of acrylnitrile or methacrylnitrile with acrylic acid esters, vinyl-carboxylate esters, vinyl halides, aromatic vinyl compounds or unsaturated carboxylic acid and diene, and acrylnitrile-methylacrylate copolymers.

(21) Metals which may be useful in the foil component of the laminate are those that can be formed into a foil with the physical and chemical properties (e.g., thickness, malleability, temperature resistance and chemical compatibility) sufficient to adhere to the plastic layer(s) and remain intact during the forming processes disclosed herein. Such metals include, but are not limited to, aluminum, iron, nickel, tin, bronze, brass, gold, silver, chrome, zinc, titanium, and copper, combinations thereof, as well as alloys including the aforementioned metals, such as steel and stainless steel. The metal foil may be present in the laminate, for example, at a thickness of about 8 m to about 200 m, about 10 m to about 150 m, about 15 M to about 125 m, about 20 m to about 100 m, or about 25 m to about 80 M, and any ranges therein. In certain embodiments the foils, e.g., aluminum foil, may have a purity of at least about 98.0%, more preferably at least about 98.3%, still more preferably at least about 98.5%, and most particularly at least about 98.6%. Aluminum foils of the aluminum-iron-silicon or aluminum-iron-silicon-manganese types may also be used. Other suitable metal foils known in the art may be used as well.

(22) The laminate may also include one or more adhesive layers between the foil layer and the plastic layer. The same or different adhesives may be used to adhere the plastic to the metal foil on each side. The adhesive layer should be capable of forming a bond with the plastic layer and the foil layer, and generally should be of a thickness of between about 0.1 m and about 12 m, more typically between about 2 m and about 8 m, and any ranges therein. Any number of adhesives known in the art may be used, and the adhesives may be applied using a number of known techniques. Suitable adhesives may contain one or more solvents, be solvent-free, or may be acrylic adhesives or polyurethane adhesives. The adhesive may also be a thermal bonding adhesive, for example an ethylene-vinylacetate copolymer or a polyester resin. The adhesive may also be of a type which hardens upon exposure to electromagnetic rays, for example ultraviolet rays. The laminate may also be formed by hot calendaring, extrusion coating, co-extrusion coating or through a combination of processes. Example adhesives that may be used in the present disclosure include but are not limited to polyethylene (PE) homopolymers, such as LDPE, MDPE, LLDPE, and HDPE; PE copolymers, such as ethylene-acrylic acid copolymers (EAA), ethylene methacrylic acid copolymer (EMAA); polypropylene (PP); PP copolymers; ionomers; and maleic anhydride grafted polymers.

(23) In another embodiment, the film, e.g., a metal-plastic laminate, may feature a sealing layer in the form of a sealable film or a sealable counting on one of the outer lying sides, or on both of the outer sides. The sealing layer will be the outermost layer in the laminate. In particular, the sealing layer may be on one outer side of the film, which is directed towards the contents of the shaped packaging, in order to enable the lid foil or the like to be sealed into place.

(24) Another embodiment for forming blister packaging is a laminate of aluminum, where the metal foil is coated with a plastic on each side. Aluminum foil is known to provide superior barrier properties to protect the contents of the package. The plastic coating provides an effective means of sealing the package plus provides a protective coating for the aluminum, and may also provide the ability to print on the package.

(25) In some embodiments, the thicknesses and compositions of the laminate include but are not limited to: i. OPA/ALU/PE (12 m/60 m/30 g/m.sup.2); ii. OPA/ALU/PE (12 m/45 m/30 g/m.sup.2); iii. OPA/ALU/PVC (12 m/60 m/30 g/m.sup.2); iv. OPA/ALU/PVC (12 m/45 m/30 g/m.sup.2); v. OPA/ALU/PP (12 m/60 m/30 g/m.sup.2); and vi. OPA/ALU/PP (12 m/45 m/30 g/m.sup.2). As used above, OPA stands for oriented polyamide, ALU stands for aluminum, PE stands for polyethylene, PVC stands for polyvinylchloride, and PP stands for polypropylene.

(26) An embodiment of a turbulating piercer is shown in FIG. 1. As used herein the term turbulating piercer is meant to convey its ordinary meaning in the art, and is used to indicate that the piercer, during use, i.e. during delivery of a fluid that enters the inlet opening under pressure, creates a laminar flow as the fluid flows through the radial inlet channel and creates a turbulent flow as the fluid flows into and through the internal cavity and outlet channels or cannulae, such that the fluid is released through the outlet openings as a spray or mist rather than a stream.

(27) As shown in the FIG. 1, the piercer 10 includes a base 12, which is a circular base in the embodiments shown, and an elongated trilaterally symmetrical member 14 projected from and concentric with the center of the base 12. It is understood that the base can be provided in alternate geometrical shapes for various applications, including but not limited to oval or polygonal, for example. The projected member 14, which can also be called the piercer body or the projection can be attached to, contiguous with, or integrally formed with the base. The piercer including the base and the projection can be a single piece and configured to be held within the interior of a closed, fluid containing cavity such as the interior of a formed recess or a blister as described elsewhere herein. In particular, the piercer is configured to be used in a formed blister and delivered under pressure in devices as described in commonly owned U.S. Pat. Nos. 7,669,597, 7,963,089, 8,047,204, 8,272,194, 8,377,009, and U.S. application Ser. Nos. 13/770,861, 13/625,614, 13/233,661, 13/191,315, 13/149,584, and 12/851,524, each of which is incorporated herein by reference in its entirety.

(28) As shown in FIG. 3, the top 32 of the base provides a single inlet 34 to the internal flow path of the piercer and the projection provides one or more outlets or discharge ports 36 near the lancet for the release of the fluid contents of the blister. As seen in FIG. 7, for example, this embodiment provides a fluid path that includes at least three turns effectively of 90 as the fluid enters from the top, passes through the base and then exits through the top of the projection. It is understood that this is a preferred embodiment only and that other angles or additional angular deviations in the path can also be incorporated into the fluid path as desired to achieve a certain spray geometry. For example, angles of any size can be utilized including any acute or obtuse angle, and not limited to angles of approximately 15, 30, 45, 60, 75, 105, 120, 135, 150, 165 and combinations thereof.

(29) In the embodiment shown, three outlets are provided. The base 12 and projection 14 provide a fluid path from the interior of a blister containing the piercer into and through the base and into a central cavity 40 as shown in FIGS. 5, 7 and 10, and out through the outlet channels 42 and openings 36. The interior channel or cavity provides structures that create turbulence in a liquid that is flowing through the cavity under pressure. In the embodiment shown in the figures the fluid path includes an conduit 38 from the inlet opening 34 into the interior cavity. The cavity includes a central channel 40 and three tubular side channels 42 that lead to the three outlet openings 36 respectively. As best seen in FIG. 6, the three tubular channels are connected by angular walls 48 that form the central cavity, and the top of the cavity is formed by an inverse pyramidal configuration 50, the surfaces of which deflect the liquid flow into the three side channels. This combination of angled surfaces creates turbulence in the fluid flow as the fluid flows from the internal cavity into the delivery channels and produces the desired spray geometry for liquids expelled through the piercer.

(30) The top, or most distal end of the projection provides a piercing point or lancet 16, effective to pierce the lidstock of a blister when forced against it, as when a blister containing the piercer is crushed to dispense the contents. The size and orientation of the lancet is designed to minimize any potential interference with the spray by any flap formed in the lidstock as it is pierced by the lancet. The embodiment shown in the figures has a triangular pyramid shape with 3 bilobal discharge ports disposed around the base. It is understood that other configurations are also contemplated including, but not limited to 2, 4, 5, or six channels for example, which may be used for dispensing fluids to different parts of a user's body or for alternate non-medical uses.

(31) During use, a piercing device as described herein can be placed in a formed blister as a step in the production of a measured dosage form. The production step can be described in certain embodiments as a process for manufacturing a shaped article for unit-dose packaging with at least one formed recess, that includes (a) holding a film between at least one retaining tool and at least one die, wherein the die has at least one die opening defined by a substantially circular edge of the die opening; (b) driving a first plunger into the die opening, which causes the film to be formed into a primary contour, the contour having a depth of at least about 100% and up to about 150% of the depth of the final formed recess, and an Area Ratio of from greater than 1.1, 1.2, 1.3, 1.5 or 2.1) to about 3.0; (c) driving a second plunger into the primary contour to a depth that is less than the depth of the primary contour, wherein the second plunger forms a second geometric shape with substantially the same Area Ratio as the primary contour, the second geometric shape comprising a portion distal from the die opening edge that is sized to fit a base portion of an internal piercer comprising a base portion and a piercing tip; and (d) inserting an internal piercer into the formed recess, wherein the base portion of the internal piercer is positioned in the shape formed in the distal portion of the formed recess by the second plunger. The dosage form can then be filled with a measured quantity of a liquid or powder composition and sealed, all within a sterile cabinet, room or machine.

(32) The formed blister, either individually or in a multiple blister pack or strip, is placed in a dispensing device. In certain embodiments a dispensing device can be described as typically including a body with a nozzle end for directing a spray or mist into the eye, ear, nose or throat of a user, a trigger device to be operated by a user, a dosage form, a cavity to contain the dosage form as described herein, a plunger or piston body, an actuator mechanism linking the trigger device to the plunger, a piercing mechanism positioned to pierce the dosage form upon activation of the trigger, and a discharge channel to release a spray of the liquid composition through the nozzle in a predetermined spray plume geometry and direction. In certain embodiments the trigger mechanism can include a mechanical advantage, a mechanical disadvantage or both, or the system may be fired by an electromechanical mechanism in order to ensure that the device can be operated by a person with limited strength, and also to ensure that the blister is crushed with sufficient force to dispense the contents in the desired spray geometry.

(33) All of the devices and methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the devices and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the devices and/or methods and in the steps or in the sequence of steps of the methods described herein without departing from the concept, spirit and scope of the invention. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.