Dispenser for dispensing beneficial agent

• US 4,290,426 A
• Filed: 12/31/1979
• Issued: 09/22/1981
• Est. Priority Date: 05/04/1978
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Theeuwes, Felix, Luschen, Joseph G.
• Primary Examiner(s): ROSENBAUM, C FRED
• Application Number:
  US06/108,515
• Time in Patent Office: 631 Days
• Field of Search: 128/127, 128/130, 128/222, 128/260-261, 128/270-271, 424/16, 424/19, 424/22
• US Class Current: 424/428
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50

Abstract

A dispenser is disclosed for dispensing a beneficial agent to a fluid environment. The dispenser comprises an impermeable container, a reservoir, a passageway, a beneficial agent, and a polymeric agent. In operation, beneficial agent is dispensed by fluid entering the reservoir motivating the polymeric agent to undergo fluid induced transition to a viscofluid, with beneficial agent dispensed by (a) viscofluid exiting through the passageway and transporting beneficial agent concurrently therewith, or by (b) beneficial agent exhibiting an increased coefficient of diffusion in the viscofluid and diffusing therethrough to the exterior of the device. An embodiment of the invention pertaining to laminates also is disclosed as useful for manufacturing the dispenser.

Claims

1. A dispenser for the controlled dispensing of a beneficial agent to a fluid environment of use, the dispenser comprising:

(a) a container having a wall impermeable to fluid and impermeable to agent, said wall surrounding an internal reservoir having an uniform measurement along a given dimension;

(b) a passageway in the container connecting the reservoir with the exterior of the dispenser, said passageway having an area that permits entry of fluid into the reservoir, and release of beneficial agent from the reservoir;

(c) means in the reservoir for dispensing the beneficial agent from the dispenser, said means (1) occupying a volume having a constant cross-sectional area parallel to the passageway and housing the beneficial agent therein, (2) absorbs fluid that enters the reservoir and undergoes fluid induced relaxation from an unrelaxed to a relaxed state, with (3) the beneficial agent exhibiting an increased coefficient of diffusion in the relaxed means; and

,

(d) wherein, when the dispenser is in operation in the fluid environment of use, beneficial agent is dispensed by diffusion through the relaxed means and the passageway at a controlled rate from the dispenser in an amount that corresponds to the amount of agent within the means that goes from an unrelaxed to a relaxed state, which relaxation occurs at a rate governed by the progressive fluid absorption and accompanying induced relaxation of the means over time.

2. The dispenser for dispensing the beneficial agent according to claim 1, wherein the dispenser has two passageways.

3. The dispenser for dispensing the beneficial agent according to claim 1, wherein the means is lightly cross-linked.

4. The dispenser for controlled dispensing of a beneficial agent to the fluid environment according to claim 1, wherein the beneficial agent is a drug and the environment of use to an animal.

5. The dispenser for the controlled dispensing of a beneficial agent according to claim 1, wherein the dispenser is sized, shaped and adapted for dispensing beneficial agent to an oral environment of use, and said agent is a drug.

6. The dispenser for the controlled dispensing of a beneficial agent according to claim 1, wherein the dispenser is sized, shaped and adapted for dispensing a beneficial agent to an anal environment of use.

7. The dispenser for the controlled dispensing of a beneficial agent according to claim 1, wherein the dispenser is sized, shaped and adapted for dispensing beneficial agent to an ocular environment.

8. A dispenser for the controlled dispensing of a beneficial agent to a fluid environment of use, wherein said dispenser comprises:

(a) a container impermeable to fluid and impermeable to agent;

(b) a reservoir in the container;

(c) a passageway in the container connecting the reservoir with the exterior of the dispenser, said passageway having an opening that permits the entry of fluid into the reservoir and release of agent from the reservoir;

(d) means for housing and dispensing the beneficial agent from the dispenser in the reservoir, said means a transporting agent that occupies a volume having a constant cross-sectional area parallel to the passageway, absorbs fluid that enters the reservoir, undergoes relaxation, and flows through the passageway to the exterior of the dispenser transporting the agent therewith; and

,

(e) wherein, when the dispenser is in operation, the agent is dipensed in a controlled amount to the environment of use at a rate governed by the rate of relaxation and flow of the transporting means from the dispenser over a prolonged period of time.

9. The dispenser for the controlled dispensing of the beneficial agent according to claim 8, wherein the beneficial agent is a drug, and the environment of use is an animal.

10. The dispenser for the controlled dispensing of the beneficial agent according to claim 8, wherein the dispenser has two passageways.

11. The dispenser for the controlled dispensing of the beneficial agent according to claim 8, wherein the means is lightly cross-linked.

12. The dispenser for the controlled dispensing of the beneficial agent according to claim 8, wherein the dispenser is sized, shaped and adapted for dispensing a beneficial agent to an oral environment of use.

13. The dispenser for the controlled dispensing of the beneficial agent according to claim 8, wherein the dispenser is sized, shaped and adapted for dispensing the beneficial agent to an anal environment of use.

14. The dispenser for the controlled dispensing of the beneficial agent according to claim 8, wherein the dispenser is sized, shaped and adapted for dispensing the beneficial agent to an ocular environment of use.

15. The dispenser for the controlled dispensing of the beneficial agent according to claim 8, wherein the passageway has an area that permits the simultaneous entry of fluid into the reservoir and the release of beneficial agent from the reservoir, and the transporting agent maintains a constant cross-sectional area in reference to the passageway.

16. The dispenser for the controlled dispensing of the beneficial agent according to claim 8, wherein the fluid is water.

17. The dispenser for the controlled dispensing of the beneficial agent according to claim 8, wherein the beneficial agent is a member selected from the group consisting of central nervous system, autonomic nervous system, hypnotic, sedative, psychic energizers, tranquilizers, anticonvulsants, muscle relaxants, antiparkinson, analgesic, antipyretic, anti-inflammatory, anesthetic, antispasmodic, muscle contractant, antimicrobial, antimalarial, hormonal, progestational, estrogenic, androgenic, corticoid, sympathomimetic, cardiovascular, diuretic, antiparasite, neoplastic, hypoglycemic, nutritional, vitamin, and ocular drugs.

18. The dispenser for the controlled dispensing of the beneficial agent according to claim 8, wherein the dispenser has two passageways and the means has an uniform cross-sectional area parallel to the passageways during the dispensing period.

19. The dispenser for the controlled dispensing of the beneficial agent to a fluid environment of use, said dispenser comprising:

(a) a container having a wall that surrounds an internal reservoir, said wall formed of a polymer selected from the group consisting of acrylonitrile-styrene copolymer, acrylonitrile-butadiene-styrene terpolymer, poly(monochlorotrifluoroethylene), poly(tetrafluorethylene), tetrafluoroethylenehexafluoroethylene copolymer, poly(vinylidene chloride), vinylidene chloride-vinyl chloride copolymer, poly(styrene), butadiene-styrene copolymer, chlorosulfonated polyethylene-styrene copolymer, vinyl chloride-acrylonitrile copolymer, poly(vinyl chloride), vinylidene chloride-alkylacrylate copolymer, poly(cyclohexane-dimethanolterphthalate), poly(carbonate) and rubber;

(b) a passageway in the container connecting the reservoir with the exterior of the device, said passageway having an area that permits the entry of fluid into the reservoir, and the release of agent from the reservoir; and

,

(c) means in the reservoir for dispensing the agent from the dispenser, said means (1) containing the agent mixed therein, (2) absorbs fluid that enters the reservoir and undergoes fluid induced relaxation from an unrelaxed to and relaxed state, with (3) the agent exhibiting an increased coefficient of diffusion in the relaxed state, and (4) passing through the relaxed means and the passageway to the exterior of the dispenser for dispensing of agent at a controlled rate over time.

20. A dispenser for the controlled dispensing of a beneficial agent to a fluid environment of use, said dispenser comprising:

(a) a container having a wall that surrounds and forms an internal reservoir, said wall a polymer selected from the group consisting of acrylonitrile-styrene copolymer, acrylonitrile-butadiene-styrene terpolymer, poly(monochlorotrifluoroethylene), poly(tetrafluoroethylene), tetrafluoroethylenehexafluoroethylene copolymer, poly(vinylidene halide), poly(vinylidene chloride), vinylidene chloride-vinyl chloride copolymer, polymer(styrene), butadiene-styrene copolymer, chlorosulfonated polyethylene-styrene copolymer, vinyl chloride-acrylonitrile copolymer, poly(vinyl chloride), vinylidene chloride-acrylonitrile copolymer, poly(vinyl chloride), vinylidene chloride-alkylacrylate copolymer, poly(cyclohexane dimethanol-terphthalate), poly(carbonate) and rubber;

(b) a passageway in the container wall connecting the reservoir with the exterior of the dispenser, said passageway having an area that permits the entry of fluid into the reservoir and the release of agent from the reservoir, and,

(c) means for dispensing the beneficial agent from the device in the reservoir, said means a transporting agent having the agent therein, which means absorbs fluid that enters the reservoir, undergoes relaxation and flows through the passageway to the exterior of the dispenser transporting the agent concurrently therewith at a controlled rate governed by the rate of relaxation of the transporting means over time.

21. A dispenser for the controlled dispensing of a beneficial agent to a biological fluid environment of use, wherein said dispenser comprises:

(a) container having a wall impermeable to fluid and impermeable to agent, said wall surrounding an internal reservoir;

(b) a passageway in the wall connecting the reservoir with the exterior of the dispenser, said passageway having an opening that permits the entry of the biological fluid into the reservoir and release of agent from the reservoir;

(c) means in the reservoir housing the agent, said means absorbing fluid that enters the reservoir and undergoes fluid induced relaxation from an unrelaxed to a relaxed means with the agent exhibiting an increased coefficient of diffusion in the relaxed means, which means is a member selected from the group consisting of poly(hydroxyalkyl methacrylate), poly(acrylamide), poly(methacrylamide), poly(N-vinyl-2-pyrrolidone), dextrin, anionic and cationic hydrogels, organic poly(electrolyte) complexes, poly(alkylene oxide), lightly cross-linked poly(vinyl alcohol), poly(glyceryl methacrylate), poly(hydroxypropyl methacrylate), poly(sulphide), poly(sulphoxide), poly(sulphone), poly(styrene), copolymeric divinylbenzene-styrene, poly(diakylaminoethyl styrene), cation-exchange resins, anion-exchange resins, sulfonated copolymers of styrene and divinyl-benzene, copolymers of methacrylic acid and divinylbenzene; and

,

(d) wherein, when the dispenser is in operation in the fluid environment of use, beneficial agent is dispensed by diffusion through the relaxed means and the passageway from the dispenser at a rate governed by the progressive fluid absorption and accompanying fluid induced relaxation of the means over a prolonged period of time.

22. A dispenser for dispensing a beneficial agent at an oscillating rate of release to a fluid environment of use, wherein said dispenser comprises:

(a) a container having a wall made of a material that is substantially impermeable to the passage of fluid and substantially impermeable to the passage of agent, which wall surrounds and forms;

(b) an internal reservoir having a cross-sectional area that changes periodically from a maximum to a minimum area along one dimension;

(c) a passageway in the wall of the container connecting the reservoir with the exterior of the dispenser;

(d) means in the reservoir for dispensing the beneficial agent from the dispenser, said means having a cross-sectional area that corresponds to the reservoir, houses the beneficial agent, and absorb fluid and undergoes relaxation; and

,

(e) wherein, when the dispenser is in operation, fluid enters the reservoir, with the beneficial agent dispensed at an oscillating rate in an amount that corresponds to the amount of agent in the means that undergoes relaxation as it cross-sectional area changes throughout the device.

23. The dispenser for dispensing the beneficial agent according to claim 22, wherein the wall exhibits a frequency of change in shape that corresponds to the periodic changes of the reservoir.

24. A dispenser for dispensing a beneficial agent at an oscillating rate of release to a fluid environment of use, wherein said dispenser comprises:

(a) a container having a wall made of a material that is substantially impermeable to the passage of fluid and substantially impermeable to the passage of agent, which wall increases in length outwardly then decreases in length inwardly along the axis of the device over the length of the device, which wall surrounds and forms;

(b) an internal reservoir having a cross-sectional area that changes periodically from a maximum to a minimum area along one dimension;

(c) a passageway in the wall of the container connecting the reservoir with the exterior of the dispenser;

(d) means in the reservoir for dispensing the beneficial agent from the dispenser, said means having a cross-sectional area that corresponds to the reservoir, houses the beneficial agent, and absorbs fluid and undergoes relaxation; and

,

(e) wherein, when the dispenser is in operation fluid enters the reservoir, with the beneficial agent dispensed at an oscillating rate in an amount that corresponds to the amount of agent in the means that undergoes relaxation as it cross-sectional area changes throughout the device.

25. A dispenser for dispensing a beneficial agent in a fluid environment of use at a gradually increasing rate of release followed by a substantially zero order rate of release over a prolonged period of time, wherein said device comprises:

(a) a container having a wall made of a material that is substantially impermable to the passage of fluid and substantially impermeable to the passage of agent, said container having a lead end that gradually increases in size followed by the remainder of the container having constant dimensions, with the wall surrounding and forming;

(b) an internal reservoir;

(c) a passageway in the lead end of the wall connecting the reservoir with the exterior of the device;

(d) means in the reservoir for dispensing agent from the dispenser, said means occupying a shape that corresponds to the shape of the reservoir, housed the beneficial agent, absorbs fluid and undergoes relaxation in the presence of the fluid, and,

(e) wherein, when the dispenser is in the environment of use, fluid enters the reservoir urging the means to undergoes relaxation, which dispenses agent from the device at a gradually increasing rate followed by a zero order rate that corresponds to shape and rate at which the means undergoes relaxation over time.