United States Patent:  6,113,938

Assignee:  ALZA Corporation (Mountain View, CA)

Filed:  July 24, 1998

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.

SUMMARY OF THE INVENTION

In accordance with the present invention, a delivery system for controlled delivery of a beneficial agent includes an implantable capsule having an opening, a beneficial agent reservoir within the capsule for delivery of the beneficial agent at a predetermined delivery rate, and a membrane plug received in the opening of the capsule. The membrane plug provides a fluid permeable barrier between an interior and an exterior of the capsule. The membrane plug has 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 is preselected to achieve the predetermined delivery rate at which the beneficial agent is delivered from the reservoir.

In accordance with another aspect of the present invention, a method of forming a beneficial agent delivery device includes the steps of 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, and selecting a membrane plug having a plurality of retention ribs and a core diameter between the ribs. 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. The open end of the chamber is plugged with the selected membrane plug.

According to a further aspect of the invention, a method of making an osmotic delivery device for the delivery of beneficial agents includes the steps of filling a reservoir in a 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 fluids 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 varying a clearance between the membrane plug and an interior of the body.

In accordance with an additional aspect of the present invention, a method of controlling a release rate of an osmotic delivery device for delivery of beneficial agents includes 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. The release rate of the beneficial agent from the body is controlled 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.

The present invention provides the advantage of a more controllable beneficial agent delivery rate by preventing constraint of a membrane plug.

The present invention also provides an advantage of allowing control of a beneficial agent delivery rate without changing a shape of an implant capsule or a material of a membrane plug.

In addition, the present invention allows the control of a beneficial agent delivery rate by changing a membrane shape or an implant capsule shape.

Claim 1 of 16 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.

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