Dual rate agent delivery device

• US 5,240,713 A
• Filed: 09/27/1991
• Issued: 08/31/1993
• Est. Priority Date: 09/27/1991
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Ayer, Atul D.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): HORNE, LEON
• Application Number:
  US07/767,308
• Time in Patent Office: 704 Days
• Field of Search: 424/473, 424/472, 424/468, 424/438, 604/891.1
• 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 a long-term dispensing device for the controlled delivery of a beneficial agent in a hydrophilic carrier, which device quickly and continuously delivers an effective amount of agent followed by a continuous and sustained delivery of agent in a controlled and uniform amount over a prolonged period of time, thus providing for delivery of beneficial agent to an environment of use at two different rates and having a fast startup.

Claims

1. A delivery device for dispensing a beneficial agent to an environment of use at two different rates and having a faster startup, where the device comprises:

a) a housing comprised of a wall surrounding an internal compartment, the wall being semipermeable in at least a portion;

b) a first beneficial agent formulation, comprising a first beneficial agent and a pharmaceutically acceptable hydrophilic carrier, in the compartment;

c) a second beneficial agent formulation, comprising a second beneficial agent and a pharmaceutically acceptable hydrophilic carrier, in the compartment;

d) a first exit means within that portion of the wall of the housing in contact with the first beneficial agent formulation, the exit means comprising an exit passageway or a multiplicity of exit passageways, the diameter of each passageway being of a size to provide rapid and continued delivery of the first beneficial agent for a first time period;

e) a second exit means in the compartment between the first beneficial agent formulation and the second beneficial agent formulation, the second exit means comprising an exit partition layer having an exit passageway or a multiplicity of exit passageways, the diameter of each passageway being of a size for maximizing the release of the second beneficial agent by osmotic pumping and minimizing the release of the beneficial agent by diffusion or erosion to provide continuous and sustained delivery in a controlled and uniform manner over a prolonged period of time; and

f) an expandable driving member in the compartment.

2. A delivery device according to claim 1 wherein the first beneficial agent and the second beneficial agent are the same beneficial agent.

3. A delivery device according to claim 1 wherein the beneficial agent is an ionophore.

4. A delivery device according to claim 2 wherein the beneficial agent is an ionophore.

5. A delivery device according to claim 3 wherein the ionophore is lysocellin, lasalocid, tetronasin or laidlomycin propionate.

6. A delivery device according to claim 4 wherein the ionophore is lysocellin, lasalocid, tetronasin or laidlomycin propionate.

7. A delivery device according to claim 1 wherein the diameter of each of the first exit passageways is 100 mil or larger, and the diameter of each of the second exit passageways is from about 60 mil to about 95 mil.

8. A delivery device according to claim 7 wherein the beneficial agent is an ionophore.

9. A delivery device according to claim 8 wherein the first beneficial agent and the second beneficial agent are the same ionophore, and the ionophore is chosen from lysocellin, lasalocid, tetronasin and laidlomycin propionate.

19. A delivery device according to claim 1 wherein the environment of use is the rumen of a ruminant animal and the delivery device further comprises a density element.

20. A delivery device according to claim 7 wherein the environment of use is the rumen of a ruminant animal, the delivery device further comprises a density element, and the beneficial agent is an ionophore.

21. A delivery device according to claim 20 wherein the first beneficial agent and the second beneficial agent are the same ionophore, and the ionophore is chosen from lysocellin, lasalocid, tetronasin and laidlomycin propionate.

10. A method for dispensing a beneficial agent to an environment of use at two different rates and having a faster startup, the method comprising the steps of:

(1) admitting into the environment of use a dispenser comprising;

a) a housing comprised of a wall surrounding an internal compartment, the wall being semipermeable in at least a portion;

b) a first beneficial agent formulation, comprising a first beneficial agent and a pharmaceutically acceptable hydrophilic carrier, in the compartment;

c) a second beneficial agent formulation, comprising a second beneficial agent and a pharmaceutically acceptable hydrophilic carrier, in the compartment;

d) a first exit means within that portion of the wall of the housing in contact with the first beneficial agent formulation, the exit means comprising an exit passageway or a multiplicity of exit passageways, the diameter of each passageway being of a size to provide rapid and continued delivery of the first beneficial agent for a first time period;

e) a second exit means in the compartment between the first beneficial agent formulation and the second beneficial agent formulation, the second exit means comprising an exit partition layer having an exit passageway or a multiplicity of exit passageways, the diameter of each passageway being of a size for maximizing the release of the second beneficial agent by osmotic pumping and minimizing the release of the beneficial agent by diffusion or erosion to provide continuous and sustained delivery in a controlled and uniform manner over a prolonged period of time; and

f) an expandable driving member in the compartment;

(2) imbibing fluid through the semipermeable wall at a rate determined by the permeability of the wall and the osmotic pressure gradient across the wall, which fluid contacts the formulation comprising the beneficial agent to form a dispensable composition and contacts the expandable driving member to cause the expandable driving member to expand and push against the agent composition;

(3) quickly delivering the first beneficial agent from the compartment by the first beneficial agent formulation being dispensed in a beneficially effective amount through the first exit means by diffusion or erosion into the environment of use for a first period of time; and

(4) delivering the second beneficial agent from the compartment by the expandable driving member continually expanding against the second beneficial agent formulation and causing the beneficial agent to be dispensed in a beneficially effective amount through the second exit means at a controlled rate to the environment of use over a prolonged period of time

11. A method according to claim 10 wherein the environment of use is the rumen of a ruminant animal and the dispenser further comprises a densifier.

12. A method according to claim 11 wherein the first beneficial agent and the second beneficial agent are the same beneficial agent.

13. A method according to claim 11 wherein the beneficial agent is an ionophore.

14. A method according to claim 12 wherein the beneficial agent is an ionophore.

15. A method according to claim 14 wherein the ionophore is lysocellin, lasalocid, tetronasin or laidlomycin propionate.

16. A method according to claim 10 wherein the diameter of each of the first exit passageways is 100 mil or larger, and the diameter of each of the second exit passageways is from about 60 mil to about 95 mil.

17. A method according to claim 16 wherein the environment of use is the rumen of a ruminant animal, the dispenser further comprises a densifier, and the beneficial agent is an ionophore.

18. A method according to claim 17 wherein the first beneficial agent and the second beneficial agent are the same ionophore, and the ionophore is chosen from lysocellin, lasalocid, tetronasin and laidlomycin propionate.