Laminate device for controlled and prolonged release of substances to an ambient environment and method of use

• US 4,601,893 A
• Filed: 12/06/1984
• Issued: 07/22/1986
• Est. Priority Date: 02/08/1984
• Status: Expired due to Term

• Current Assignee: Pfizer Inc.
• Original Assignee: Pfizer Inc.
• Inventors: Cardinal, John R.
• Primary Examiner(s): Niebling, John F.
• Assistant Examiner(s): Chapman, Terryence
• Application Number:
  US06/678,722
• Time in Patent Office: 593 Days
• Field of Search: 424/DIG. 7, 424/15, 424/16, 424/19, 424/21, 604/890, 604/892
• US Class Current: 424/424
• CPC Class Codes: A61K 9/70 Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092
• 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

Laminate device for the controlled and prolonged release of at least one active agent to an ambient environment comprising at least one core sheet, said core sheet or sheets comprising said agent or agents in a polymer matrix, and, in a preferred embodiment, a porosity enhancing agent in admixture with said agent; said core sheet or sheets being alternately sandwiched or interposed between coextensive inert polymeric films substantially impermeable to said environment and to said agent or agents, said device being perforated by one or a plurality of macroholes extending through said sheets and said films. In a modification of said device the perimeter edge thereof is coated by an inert polymeric film substantially impermeable to said environment and to said agent or agents. Also included are methods for making such a device.

Claims

1. A device for controlled and prolonged release of at least one active agent to an ambient environment comprising

at least one core sheet sandwiched between coextensive polymeric films which are substantially impermeable to said environment and to said agent,

said core sheet comprising a mixture of said agent in a polymer matrix,

said device having one or a plurality of macroperforations extending through said films and said core sheet,

the diameter and arrangement of said macroperforations in relation to the thickness of said core sheet being selected to expose sufficient interior edge area of said sheet to said environment to afford the desired release rate of said agent.

2. The device of claim 1 wherein said macroperforations are symmetrically distributed over the face of said device and said core sheet comprises a homogenous mixture of active agent in the polymer matrix.

3. The device of claim 1 wherein said macroperforations are circular to afford interior edges of cylindrical configuration for exposure of said agent to said environment.

4. The device of claim 3 wherein said macroperforations are from about 0.5 to 10 mm in diameter.

5. The device of claim 1 wherein the perimeter edge of said core sheet is coated by a film substantially impermeable to said environment and to said agent.

6. The device of claim 1 wherein said agent is dissolved in said core sheet.

7. The device of claim 1 wherein said agent is dispersed in said core sheet.

8. The device of claim 1 wherein said agent is released by vaporization into a gaseous environment.

9. The device of claim 1 wherein said agent is released into a liquid environment in which said agent exhibits a finite solubility and in which said film and said core polymers are substantially insoluble.

10. The device of claim 9 wherein said agent is present at a level of from about 0.1 to 75 weight % of said core sheet.

11. The device of claim 9 wherein said core sheet contains a dispersed porosigen of finite solubility in said environment.

12. The device of claim 9 wherein said agent is characterized by finite solubility in an aqueous environment.

13. The device of claim 12 wherein said agent is a drug.

14. The device of claim 12 for oral administration to a ruminant, wherein said film and said core sheet are flexible and resilient and capable of constrainment in rolled configuration by constraining means releasable in an aqueous environment.

15. The device of claim 14 wherein said agent is an anthelmintic agent.

16. The device of claim 15 wherein said agent is a water-soluble acid addition salt of morantel, pyrantel or levamisole.

17. The device of claim 16 wherein said agent is morantel citrate.

18. The device of claim 16 wherein said agent is morantel tartrate.

19. A device for controlled and prolonged release of anthelmintic in a ruminant comprising

a resilient and flexible ethylene-vinyl acetate copolymer core sheet sandwiched between a pair of coextensive resilient films of said copolymer,

said core sheet containing from about 10 to 75% by weight of a water-soluble morantel salt dispersed therein,

said device having one or a plurality of circular macroperforations about 0.5 to 10 mm in diameter symmetrically distributed across the face of said device and extending through said films and said core sheet,

the diameter and arrangement of said macroperforations in relation to the thickness of said core sheet being selected to expose sufficient interior edge area of said sheet to afford the desired morantel release rate,

said device being capable of constrainment in rolled configuration by constraining means releasable in the rumen of an animal.

20. The device of claim 19 wherein the perimeter edge of said core sheet is sealed by a film of ethylenevinyl acetate copolymer.

21. The device of claim 19 wherein said salt is morantel citrate.

22. The device of claim 19 wherein said salt is morantel tartrate.

23. A three-layer laminate device for the controlled and continuous release of a water-soluble active agent to an aqueous liquid-containing environment over a prolonged period of time, said device comprising

(a) a core sheet comprising a water soluble active agent dispersed in an amount corresponding to from 10% to 75% by weight of said core sheet, said sheet comprising a polymeric material insoluble in said aqueous liquid-containing environment, resilient, flexible and impermeable to said agent and to said environment;

(b) said core sheet being sandwiched between two coextensive films of polymeric material which are resilient, insoluble in said aqueous liquid-containing environment, flexible and impermeable to said environment and to said agent;

(c) the thus-produced three-layer laminate having one or a plurality of macroperforations extending through said films and said core;

(d) said three-layer laminate being capable of constrainment by constraining means in a rolled-up configuration, the constraining means being operable to release the constrained laminate when said laminate is placed in an aqueous liquid-containing environment.

24. A device according to claim 23 wherein the perimeter edge of said core sheet is sealed by a polymeric material.

25. A device according to claim 23 wherein the macroperforations are from 0.5 to 10 mm in diameter.

26. A dcvice according to claim 23 wherein the aqueous liquid-containing environment is the rumeno-reticular sac of a ruminant and the active agent is a drug.

27. A device according to claim 26 wherein the drug is an anthelmintic agent.

28. A device according to claim 27 wherein said anthelmintic agent is a water-soluble acid addition salt of morantel, pyrantel or levamisole.

29. A device according to claim 28 wherein said salt is selected from the group consisting of levamisole hydrochloride and the tartrate and citrate salts of morantel and pyrantel.

30. A device according to claim 29 wherein said salt is morantel citrate.

31. A device according to claim 30 wherein said salt is morantel tartrate.

32. A method for the control of helminthiasis in ruminant animals which comprises administering to said animals for retention in the rumeno-reticular sac, a device for the controlled and continuous administration of a water soluble salt of morantel to the aqueous liquid-containing environment in said rumeno-reticular sac over a prolonged period of time, said device comprising

(a) a core sheet comprising a water soluble salt of morantel dispersed in a sheet of ethylene vinyl acetate copolymer in an amount corresponding to from 10% to 75% by weight of said core sheet, said core sheet being insoluble in said aqueous liquid-containing environment, resilient, flexible and impermeable to said morantel salt and to said environment;

(b) said core sheet being sandwiched between two coextensive polymeric films of ethylene vinyl acetate copolymer which are insoluble in said aqueous liquid-containing environment, resilient, flexible and impermeable to said environment and to said morantel salt;

(c) the thus-produced three-layer laminate having one or a plurality of macroperforations extending through all laminae;

(d) said three-layer laminate being capable of constrainment by constraining means in a rolled-up configuration, the constraining means being operable to release the constrained laminate when said laminate is placed in said aqueous liquid-containing environment.

33. The method according to claim 32 wherein the water soluble morantel salt is morantel citrate.

34. The method according to claim 32 wherein the water soluble morantel salt is morantel tartrate.

35. A method for the control of helminthiasis in ruminant animals which comprises administering to said animals for retention in the rumeno-reticular sac, a device for the controlled and continuous administration of a water soluble salt of morantel to the aqueous liquid-containing environment in said rumeno-reticular sac over a prolonged period of time, said device comprising

(a) a core sheet comprising a water soluble morantel salt dispersed in a sheet of ethylene vinyl acetate copolymer in an amount corresponding to from 10% to 75% by weight of said core sheet, said core sheet being insoluble in said aqueous liquid-containing environment, resilient, flexible and impermeable to said morantel salt and to said environment;

(b) said core sheet being coated on all sides by ethylene vinyl acetate copolymer which is insoluble in said aqueous liquid-containing environment, resilient, flexible and impermeable to said environment and to said morantel salt;

(c) the thus-produced laminate having one or a plurality of macroperforations extending through all laminae;

(d) said laminate being capable of constrainment by constraining means in a rolled-up configuration, said constraining means being operable to release the constrained laminate when said laminate is placed in said aqueous liquid-containing environment.

36. A method according to claim 35 wherein the morantel salt is morantel citrate.

37. A method according to claim 35 wherein the morantel salt is morantel tartrate.

38. A method for the control of helminths on pasture land, the helminth larvae contamination of which is at or near a minimum level, which comprises grazing on said land ruminant animals having in their rumeno-reticular sacs, a device for the controlled and continuous administration of a water soluble salt of morantel to the aqueous liquid-containing environment in said rumeno-reticular sac over a prolonged period of time, said device comprising

(a) a core sheet comprising a water soluble morantel salt dispersed in a sheet of ethylene vinyl acetate copolymer in an amount corresponding to from 10% to 75% by weight of said core sheet, said core sheet being insoluble in the aqueous liquid-containing environment, resilient, flexible and impermeable to said morantel salt and to said environment;

(b) said core sheet being coated on all sides by ethylene vinyl acetate copolymer which is insoluble in said aqueous liquid-containing environment, resilient, flexible and impermeable to said environment and to said morantel salt;

(c) the thus-produced laminate having one or a plurality of macroperforations extending through all laminae;

(d) said laminate being capable of constrainment by constraining means in a rolled-up configuration, said constraining means being operable to release the constrained laminate when said laminate is placed in said aqueous liquid-containing environment.