Rate controlled dispenser for administering beneficial agent

• US 4,684,524 A
• Filed: 08/08/1985
• Issued: 08/04/1987
• Est. Priority Date: 03/19/1984
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Landrau, Felix A., Eckenhoff, James B., Cortese, Richard
• Primary Examiner(s): Griffin, Ronald W.
• Application Number:
  US06/763,493
• Time in Patent Office: 726 Days
• Field of Search: 424/15, 424/19, 424/469, 604/890, 604/892, 514/30, 514/53
• US Class Current: 424/469
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0068 Rumen, e.g. rumen bolus

Abstract

A dispenser is disclosed for delivering a beneficial agent. The dispenser comprises (1) a housing defining an internal space, (2) a heat-responsive composition containing a beneficial agent in the space, (3) an osmotically effective solute in the space, and (4) at least one passageway in the housing for delivering the beneficial agent from the dispenser.

Claims

1. A dispenser for delivering avermectin to an environment of use, the dispenser comprising:

(a) wall means for surrounding and forming a compartment, which compartment comprises;

(1) lipophilic means for absorbing thermal energy from the enviroment of use;

(2) a beneficially effective amount of avermectin present in the means for absorbing thermal energy;

(3) osmotically active means for mixing with an aqueous fluid present in the environment of use that enters the compartment for increasing the aqueous solution volume in the compartment; and

,

(b) means in the wall for delivering avermectin from the dispenser to the environment of use over time.

2. The dispenser for delivering avermectin to the environment of use according to claim 1, wherein the avermectin is ivermectin.

3. The dispenser for delivering avermectin to the environment of use according to claim 1, wherein the wall means comprises a composition permeable to the passage of fluid.

4. The dispenser for delivering avermectin to the environment of use according to claim 1, wherein the means in the wall for delivering avermectin comprises at least one passageway formed when the dispenser is in use.

5. The dispenser for delivering avermectin to the environment of use according to claim 1, wherein the means in the wall for dispensing avermectin comprises at least one passageway formed when the dispenser is in use, and wherein the avermectin is an ivermectin.

6. The dispenser for delivering avermectin to the environment of use according to claim 1, wherein the means in the wall for delivering avermectin comprises a passageway forming material that is removed from the wall when the dispenser is in operation in the environment of use.

7. The dispenser for delivering avermectin to the environment of use according to claim 1, wherein the wall means comprise a microporous composition.

8. The dispenser for delivering avermectin to the environment of use according to claim 1, wherein the wall means comprises a microporous composition laminated in part by a semipermeable composition.

9. The dispenser for delivering avermectin to the environment of use according to claim 1, wherein the wall means comprises a semipermeable composition.

10. The dispenser for delivering avermectin to the environment of use according to claim 1, wherein the wall means comprise a polymeric composition comprising a pore former that is removed from the composition, when the dispenser is in operation in a fluid environment, to form a multiplicity of controlled porosity pores for releasing avermectin from the dispenser.

11. The dispenser for delivering avermectin to the environment of use according to claim 1, wherein osmotically active means for mixing with fluid is an osmagent that mixes with fluid that enters the compartment and continuously forms an aqueous solution.

12. The dispenser for delivering avermectin to the environment of use according to claim 1, wherein the means for absorbing thermal energy forms a dispensable composition at a temperature of from 25°

C. to 45°

C.

13. The dispenser for delivering avermectin to the environment of use according to claim 1, wherein when the dispenser is in operation in the environment of use, the means for absorbing thermal energy absorbs heat from the environment and forms a dispensable composition, and the osmotically active means imbibes fluid and forms an aqueous solution in the compartment.

14. The dispenser for delivering avermectin to the environment of use according to claim 1, wherein, the dispenser is in operation in the environment of use, the means for absorbing thermal energy absorbs thermal energy and forms a dispensable composition, the means for forming a solution imbibes fluid and forms a solution in the compartment, and the dispensable composition and the solution form in situ a substantially imniscible interface therebetween.

15. The dispenser for delivering avermectin to the environment of use according to claim 1, wherein the wall means that surrounds and forms the internal compartment comprises a member selected from the group consisting of an olefin polymer, a condensation polymer, a silicon polymer, and a carbohydrate polymer.

16. The dispenser for delivering avermectin to the environment of use according to claim 1, wherein a film is positioned between the means for absorbing thermal energy and the osmotically active means.

17. The dispenser for delivering avermectin to the environment of use according to claim 1, wherein the compartment comprises a layer of the means for absorbing thermal energy comprising avermectin.

18. The dispenser for delivering avermectin to the environment of use according to claim 1, wherein the compartment comprises a layer of the osmotically active means.

19. A dispenser for delivering a beneficial agent composition to a biological environment of use, the dispenser comprising

(a) wall means that surrounds and defines an internal compartment;

(b) means in the compartment for mixing with a beneficial agent, said means capable of changing its physical form in the presence of absorbed thermal energy from the biological environment of use;

(c) a beneficial agent mixed in the means for absorbing thermal energy;

(d) means in the compartment for imbibing an aqueous fluid present in the environment of use into the dispenser for forming continously an aqueous solution with the fluid that enters the compartment from the biological environment of use; and

,

(e) means in the wall for dispensing the beneficial agent formulation from the dispenser to the biological environment of use over time.

20. The dispenser for delivering a beneficial agent composition to the biological environment of use according to claim 19, wherein the wall means that surrounds and defines an internal compartment comprises at least in part a composition permeable to the passage of an external fluid.

21. The dispenser for delivering a beneficial agent composition to the biological environment of use according to claim 19, wherein the means in the compartment for absorbing energy is in layered arrangement with the means for forming a solution.

22. The dispenser for delivering a beneficial agent composition to the biological environment of use according to claim 19, wherein the means for continuously forming a solution in the compartment comprises an osmagent that is substantially dry when the dispenser is initially admitted into the biological environment of use.

23. The dispenser for delivering a beneficial agent composition to the biological environment of use according to claim 19, wherein the wall means that surrounds and defines the compartment comprises a first polymeric composition that permits the passage of fluid present in the environment of use and is substantially impervious to the passage of a beneficial agent, and a second polymeric composition that permits the passage of beneficial agent formulation from the dispenser.

24. The dispenser for delivering a beneficial agent composition to the biological environment of use according to claim 19, wherein the means in the wall for dispensing the beneficial agent formulation comprises at least one passageway.

25. The dispenser for delivering a beneficial agent composition to the biological environment of use according to claim 19, wherein the means in the wall for dispensing the beneficial agent formulation comprises at least one passageway formed when the dispenser is in use.

26. The dispenser for delivering a beneficial agent composition to the biological environment of use according to claim 19, wherein the means in the wall for delivering the beneficial agent formulation from the dispenser comprises a passageway forming material that is removed from the means when the dispenser is in operation in the environment of use.

27. The dispenser for delivering a beneficial agent composition to the biological environment of use according to claim 19, wherein the means in the wall for delivering the beneficial agent is a passageway connecting the exterior of the dispenser with the inside of the dispenser.

28. The dispenser for delivering a beneficial agent composition to the biological environment of use according to claim 19, wherein the wall means that surrounds and defines the compartment comprises a microporous member laminated in part by a semipermeable member.

29. The dispenser for delivering a beneficial agent composition to the biological environment of use according to claim 19, wherein the wall means that surrounds and defines the compartment comprises a microporous member laminated by a semipermeable member with a passageway through the semipermeable wall in agent releasing position with a releasing pore in the microporous member.

30. The dispenser for delivering a beneficial agent composition to the biological environment of use according to claim 19, wherein the means in the compartment for absorbing thermal energy forms a dispensable composition at a temperature of 30°

C. to 45°

C.

31. The dispenser for delivering a beneficial agent composition to the biological environment of use according to claim 19, wherein when the dispenser is in operation in the environment of use, the means for absorbing thermal energy absorbs thermal energy and forms a dispensable composition, and means for forming a solution absorbs and imbibes fluid and forms a solution in the compartment.

32. The dispenser for delivering a beneficial agent composition to the biological environment of use according to claim 19, wherein when the dispenser is in operation in the environment of use, the means for absorbing thermal energy absorbs thermal energy and forms a dispensable composition, the means for forming a solution imbibes fluid and forms a solution in the compartment, and the dispensable composition and the solution form in situ a substantially immiscible interface therebetween.

33. The dispenser for delivering a beneficial agent composition to the biological environment of use according to claim 19, wherein the wall means that surrounds and defines the internal compartment comprises a member selected from the group consisting of an olefin polymer, a condensation polymer, a silicon polymer, and a carbohydrate polymer,

34. The dispenser for delivering a beneficial agent composition to the biological environment of use according to claim 19, wherein the means in the compartment for forming a solution is separated by a film from the means for absorbing thermal energy, which film lessens the incidence of a solution formed in situ mixing with the means for absorbing thermal energy.

35. A dispenser for delivering a beneficial agent formulation to an environment of use, the dispenser comprising;

(a) a hollow body means for forming an internal lumen;

(b) a heat-sensitive lipophilic formulation means in the lumen for absorbing heat from the environment of use for forming a deliverable formulation at a temperature of at least 31°

C.;

(c) a beneficial agent mixed with the heat-sensitve formulation means;

(d) means in the lumen for forming a solution with aqueous fluid imbibed into the dispenser from the environment of use, said means forming an aqueous solution for exerting pressure against the heat-sensitive formulation means;

(e) a wall that surrounds the hollow body means, the wall comprising in at least a part a composition that is permeable to the passage of fluid; and

,

(f) passageway means in the wall for connecting the exterior of the dispenser with the interior of the dispenser for delivering the beneficial agent to the environment of use at a controlled rate over a prolonged period of time.

36. A dispenser for delivering a beneficial agent formulation to an environment of use, the dispenser comprising;

(a) a wall that surrounds and forms an internal compartment, the wall comprising at least in part a member selected from the group consisting of a cellulose ester, cellulose diester, cellulose triester, cellulose ether, cellulose ester-ether, cellulose acylate, cellulose diacylate, cellulose triacylate;

(b) a thermo-responsive composition that forms a dispensable composition when contacted by thermal energy at a temperature up to 45°

C. in the compartment, which composition is a carrier for a beneficial agent;

(c) a beneficial agent blended with the carrier which produces a beneficial effect when administered by the dispenser to an animal;

(d) an osmotically effective composition in the compartment that is substantially dry during storage temperature imbibes an aqueous fluid from the environment of use into the compartment and forms an aqueous solution at a temperature of from 30°

C. to 45°

C.; and

,

(e) means in the wall connecting the environment of use with the compartment for delivering the beneficial agent form the dispenser to the environment of use.

37. The dispenser for delivering a beneficial agent formulation to an environment of use according to claim 36, wherein the wall comprises a pore former.

38. A laminate useful for manufacturing a delivery device for dilivering a beneficial agent to a warm-blooded animal, wherein the laminate comprises (1) lamina means comprising at least in part a lipophilic member for containing a beneficial agent and for absorbing heat from the animal for forming a dispensable composition that is delivered from the delivery device to the aminal, and (2) lamina means for imbibing an aqueous fluid into the delivery device for forming an aqueous solution by mixing with fluid that enters the delivery device from the animal.

39. The laminate useful for manufacturing a delivery device for delivering a beneficial agent according to claim 38, wherein the (1) lamina means for forming a solution is an osmotically effective anhydrous solute, and the lamina for absorbing heat and the lamina for imbibing fluid are in contacting arrangement when the delivery device is in operation.

40. The lamina useful for manufacturing a delivery device for delivering a beneficial agent according to claim 38, wherein a (3) lamina means for decreasing the mixing of the (1) lamina means for absorbing heat with the (2) lamina means for forming a solution is positioned between lamina means (1) and lamina means (2).