Beneficial agent delivery system with membrane plug and method for controlling delivery of beneficial agents

• US 6,113,938 A
• Filed: 07/24/1998
• Issued: 09/05/2000
• Est. Priority Date: 12/30/1997
• Status: Expired due to Term

• Current Assignee: Intarcia Therapeutics, Inc.
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Dionne, Keith, Lautenbach, Scott, Chen, Guohua, Hom, Lawton
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US09/121,835
• Time in Patent Office: 774 Days
• Field of Search: 424/423
• US Class Current: 424/423
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas

Abstract

An osmotic delivery system for controlled delivery of a beneficial agent includes an implant capsule containing a beneficial agent and an osmotic agent which swells on contact with water causing the release of the beneficial agent over time. The osmotic delivery system has a membrane plug which allows water to pass through the plug from an exterior of the capsule while preventing the compositions within the capsule from passing out of the capsule. A delivery rate for delivery of the beneficial agent from the implant capsule is controlled by varying a core diameter of the membrane plug within a constant diameter capsule. The membrane plug has a variable water permeation rate depending on an extent to which the membrane plug is constrained by the capsule walls.

Claims

1. A delivery system for controlled delivery of a beneficial agent at a predetermined delivery rate comprising:

an implantable capsule having an opening;

a beneficial agent reservoir within the capsule for containing the beneficial agent;

a membrane plug received in the opening of the capsule and providing a fluid permeable barrier between an interior and an exterior of the capsule, the membrane plug having a plurality of external ribs for engaging an interior surface of the capsule; and

a clearance between exterior surfaces of the membrane plug and the interior surfaces of the capsule, wherein the predetermined delivery rate at which the beneficial agent is delivered from the reservoir is achieved by selecting the clearance, wherein the clearance is a difference between an exterior diameter of the external ribs and an interior diameter of the capsule, and the external ribs are between about -1% and about 8% larger than an interior diameter of grooves in the capsule.

2. The delivery system according to claim 1, wherein the clearance is a difference between an exterior diameter of the membrane plug between the ribs and an interior diameter of the capsule.

4. The delivery system according to claim 1, wherein the clearance is preselected by selecting a height of the ribs in a direction parallel to a longitudinal axis of the delivery system.

5. The delivery system according to claim 1, wherein a largest diameter of the plurality of ribs is greater than an interior diameter of the cylindrical opening of the capsule.

7. The delivery system according to claim 1, wherein a core of the membrane plug between the plurality of ribs is generally cylindrical in shape.

8. The delivery system according to claim 1, further comprising a movable piston positioned within the implant capsule and separating the beneficial agent reservoir from an osmotic agent reservoir.

3. A delivery system for controlled delivery of a beneficial agent comprising:

an implantable capsule having an opening;

a beneficial agent reservoir within the capsule for delivery of the beneficial agent at a predetermined delivery rate;

a membrane plug received in the opening of the capsule and providing a fluid permeable barrier between an interior and an exterior of the capsule, the membrane plug having a plurality of external ribs for engaging an interior surface of the capsule;

a clearance between exterior surfaces of the membrane plug and the interior surfaces of the capsule preselected to achieve the predetermined delivery rate at which the beneficial agent is delivered from the reservoir; and

wherein the diameter of the membrane plug between the ribs is between 0.5 and 15 percent smaller than the interior diameter of the capsule.

6. A delivery system for controlling delivery of a beneficial agent comprising:

an implantable capsule having an opening;

a beneficial agent reservoir within the capsule for delivery of the beneficial agent at a predetermined delivery rate;

a membrane plug received in the opening of the capsule and providing a fluid permeable barrier between an interior and an exterior of the capsule, the membrane plug having a plurality of external ribs for engaging an interior surface of the capsule;

a clearance between exterior surfaces of the membrane plug and the interior surfaces of the capsule preselected to achieve the predetermined delivery rate at which the beneficial agent is delivered from the reservoir; and

wherein the plurality of ribs are annular ribs each having a tapered leading edge in a direction of insertion of the membrane plug.

9. A method of forming a beneficial agent delivery device comprising:

filling a chamber of a delivery device capsule with a beneficial agent;

selecting a delivery rate for delivery of the beneficial agent from the chamber of the delivery device capsule;

selecting a membrane plug having a plurality of retention ribs and a core diameter between the ribs, wherein a clearance between the membrane plug and an interior surface of the delivery device capsule is selected to achieve the predetermined delivery rate for delivery of the beneficial agent, wherein the clearance is a difference between an exterior diameter of the external ribs and an interior diameter of the capsule and wherein the external ribs are between about -1% and about 8% larger than an interior diameter of grooves in the capsule; and

plugging an open end of the delivery device capsule with the selected membrane plug.

10. The method of forming a delivery device according to claim 9, wherein the clearance is a difference between the core diameter of the membrane plug and an interior diameter of the capsule.

11. The method of forming a delivery device according to claim 10, wherein the core diameter of the membrane plug is between 0.5 and 15 percent, smaller than the interior diameter of the capsule.

12. The method of forming a delivery device according to claim 9, wherein the clearance is determined by a height of the ribs in a direction parallel to a longitudinal axis of the delivery device.

13. The method of forming a delivery device according to claim 9, wherein the membrane plug is selected from a plurality of plugs having rib diameters which are the same and having different core diameters.

14. A method of making an osmotic delivery device for delivery of beneficial agents comprising:

filling a reservoir in a delivery device body with a beneficial agent and an osmotic agent;

providing a membrane plug for sealing an opening in the body, the membrane plug formed of a material which allows aqueous fluid to pass through the membrane into the osmotic agent and prevents the osmotic agent from passing out of the body; and

compensating for variations in raw materials used for the membrane plug by changing a clearance between the membrane plug and an interior of the body, wherein compensation for variations in the raw materials is performed by selecting a membrane plug having a core diameter between a plurality of ribs which is between 0.5 and 15 percent smaller than an interior diameter of the body.

15. The method of making an osmotic delivery device according to claim 14, wherein a piston is positioned in the body between the beneficial agent and the osmotic agent.

16. A method of controlling a release rate of an osmotic delivery device for delivery of beneficial agents comprising:

providing a delivery device body with a reservoir containing a beneficial agent, a beneficial agent delivery outlet through which the beneficial agent is released, an osmotic agent, and a membrane plug positioned between the osmotic agent and an exterior of the body, the membrane plug allowing aqueous fluid to pass into the reservoir to swell the osmotic agent while preventing fluid from passing out of the body through the membrane plug, the membrane plug having a diameter which fits into an end of the reservoir; and

controlling the release rate of the beneficial agent from the body by selecting a clearance between the membrane plug and an interior of the body such that a release rate of a delivery device with a smaller clearance is lower than a release rate of a delivery device with a larger clearance, wherein the clearance is selected such that external ribs of the membrane plug are between about -1% and about 8% larger than an interior diameter of groves in the device body.