Delivery system comprising means for controlling internal pressure

• US 5,474,785 A
• Filed: 07/15/1993
• Issued: 12/12/1995
• Est. Priority Date: 01/24/1990
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Eckenhoff, James B., Wright, Jeremy C., Peery, John R., Maruyama, Frederick H.
• Primary Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US08/092,301
• Time in Patent Office: 880 Days
• Field of Search: 424/473, 424/438
• US Class Current: 424/473
• 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

The present invention is directed to an improvement in a delivery system, the system comprising a wall that surrounds an internal lumen or compartment which contains a thermo-responsive beneficial agent formulation, an expandable driving member and an optional density member, and having an exit opening, and wherein the improvement comprises a) a viscosity-inducing amount of an inert viscosity-inducing agent in the thermo-responsive beneficial agent composition for increasing the viscosity of the beneficial agent composition, and/or b) a pressure-inducing exit member in the exit opening in the wall for increasing the pressure inside the lumen.

Claims

1. An improved delivery system for administering a beneficial agent to an environment of use, the delivery system comprising:

i) a wall that surrounds a lumen, the wall comprising in at least a part a semipermeable composition,

ii) a thermo-responsive composition in the lumen that forms a dispensable formulation at the temperature of the environment of use,

iii) a beneficial agent mixed with the thermo-responsive composition,

iv) an expandable driving member in the lumen for displacing the thermo-responsive composition from the delivery system, and

v) an exit opening in the wall that communicates with the lumen;

wherein, the improvement comprises;

a) a viscosity-inducing amount of an inert viscosity-inducing agent in the thermo-responsive composition for increasing the viscosity of the thermo-responsive composition, and

b) a pressure-inducing exit member in the exit opening in the wall for increasing the pressure inside the lumen, the exit member having from 1 to exit ports or passageways;

wherein the delivery system when in operation develops an internal pressure such that the pressure differential generated by the thermo-responsive composition and the exit member is greater than 1.5 psi.

2. An improved delivery system according to claim 1 wherein the viscosity-inducing agent comprises silicon.

3. An improved delivery system according to claim 1 wherein the viscosity-inducing agent is selected from the group consisting of silica, sand, precipitated silica, amorphous silica, silicon dioxide, colloidal silicon dioxide, fused silica, fumed silica, quartz, silica gel, and a siliceous composition.

4. An improved delivery system according to claim 1 wherein the viscosity-inducing agent increases the stress to flow of the thermo-responsive composition.

5. An improved delivery system according to claim 1 wherein the exit member is a releasable pressure-inducing exit member positioned in the exit opening in the wall.

6. An improved delivery system according to claim 1 where n the exit member is an insert for placement in the exit opening in the wall of the dispenser.

7. An improved delivery system according to claim 1 where n the exit member is selected from a grid, a perforated plate, a plurality of capillaries, and a plurality of tubes.

8. An improved delivery system according to claim 6 wherein the exit member is selected from a grid, a perforated plate, a plurality of capillaries, and a plurality of tubes.

9. An improved delivery system according to claim 1 wherein the beneficial agent is avermectin or ivermectin.

10. An improved delivery system according to claim 1 wherein the driving member comprises an osmagent, an osmopolymer or an osmagent together with an osmopolymer.

11. An improved delivery system according to claim 1 wherein the dispenser further comprises an inert partition layer in the lumen between the thermo-responsive composition and the driving member.

12. An improved delivery system according to claim 1 wherein the delivery system further comprises a density member in the lumen for maintaining the delivery system in the environment of use over time, the density member having a density greater than the density of the environment of use.

13. An improved delivery system according to claim 12 wherein the density member comprises a weight with a bore in the weight, and the exit member is in contact with the bore.

14. An improved delivery system according to claim 1 wherein the environment of use is an animal.

15. An improved delivery system according to claim 12 wherein the environment of use is a ruminant animal.

16. An improved delivery system for administering a beneficial agent to an environment of use, the delivery system comprising:

i) a wall that surrounds a lumen,

ii) a thermo-responsive composition in the lumen,

iii) a beneficial agent mixed with the thermo-responsive composition,

iv) an expandable driving member in the lumen for displacing the thermo-responsive composition from the dispenser, and

v) an exit opening in the wall that communicates with the lumen;

wherein, the improvement comprises;

a) a viscosity-inducing amount of an inert viscosity-inducing agent mixed into the thermo-responsive composition for increasing the viscosity of the thermo-responsive composition to increase the internal pressure of the dispenser;

wherein the delivery system when in operation develops an internal pressure such that the pressure differential generated by the thermo-responsive composition and the exit opening is greater than 1.5 psi.

17. An improved delivery system according to claim 16 wherein the viscosity-inducing agent comprises silicon.

18. An improved delivery system according to claim 16 wherein the viscosity-inducing agent is selected from the group consisting of silica, sand, precipitated silica, amorphous silica, silicon dioxide, colloidal silicon dioxide, fused silica, fumed silica, quartz, silica gel, and a siliceous composition.

19. An improved delivery system according to claim 16 wherein the viscosity-inducing agent increases the stress to flow of the thermo-responsive composition.

20. An improved delivery system according to claim 16 wherein the dispenser further comprises an inert partition layer in the lumen between the thermo-responsive composition and the driving member.

21. An improved delivery system according to claim 16 wherein the delivery system further comprises a density member in the lumen for maintaining the delivery system in the environment of use over time, the density member having a density greater than the density of the environment of use.

22. An improved delivery system for administering a beneficial agent to an environment of use, the delivery system comprising:

i) a wall that surrounds a lumen,

ii) a thermo-responsive composition in the lumen,

iii) a beneficial agent mixed with the thermo-responsive composition,

iv) an expandable driving member in the lumen for displacing the thermo-responsive composition from the dispenser, and

v) an exit opening in the wall that communicates with the lumen;

wherein, the improvement comprises;

a) a pressure-inducing exit member in the exit opening in the wall for increasing the pressure inside the lumen, the exit member having from 1 to 200 exit ports or passageways;

wherein the delivery system when in operation develops an internal pressure such that the pressure differential generated by the thermo-responsive composition and the exit member is greater than 1.5 psi.

23. An improved delivery system according to claim 22 wherein the exit member is a releasable pressure-inducing exit member.

24. An improved delivery system according to claim 22 wherein the exit member is an insert for placement in the exit opening in the wall of the delivery system.

25. An improved delivery system according to claim 22 wherein the exit member is selected from a grid, a perforated plate, a plurality of capillaries, and a plurality of tubes.

26. An improved delivery system according to claim 24 wherein the exit member is selected from a grid, a perforated plate, a plurality of capillaries, and a plurality of tubes.

27. An improved delivery system according to claim 22 wherein the dispenser further comprises an inert partition layer in the lumen between the thermo-responsive composition and the driving member.

28. An improved delivery system according to claim 22 wherein the delivery system further comprises a density member in the lumen for maintaining the delivery system in the environment of use over time, the density member having a density greater than the density of the environment of use.

29. An improved delivery system according to claim 28 wherein the density member comprises a weight with a bore in the weight, and the exit member is in contact with the bore.