Intarcia Therapeutics, Inc.

Alza Corporation

Micron Technology Incorporated

Rupal A Ayer

Guohua Chen

Catherine Manya Rohloff

Pauline C Zamora

Andrew S Luk

Paul R Houston

Stan Lam

Michael A DesJardin

Scott D Lautenbach

Michael A Desjardin

Scott D Jordan

Keith E Dionne

Steve A Berry

Craig I Rodenberger

James B Eckenhoff

Stephen A Berry

Gregory R Stewart

A nonaqueous, single-phase vehicle that is capable of suspending an active agent. The nonaqueous, single-phase vehicle includes at least one solvent and at least one polymer and is formulated to exhibit phase separation upon contact with an aqueous environment. The at least one solvent may be selected from the group consisting of benzyl benzoate, decanol, ethyl hexyl lactate, and mixtures thereof and the at least one polymer may be selected from the group consisting of a polyester, pyrrolidone, ester of an unsaturated alcohol, ether of an unsaturated alcohol, polyoxyethylenepolyoxypropylene block copolymer, and mixtures thereof. In one embodiment, the at least one solvent is benzyl benzoate and the at least one polymer is polyvinylpyrrolidone. A stable, nonaqueous suspension formulation that includes the nonaqueous, single-phase vehicle and an active agent, and a method of forming the same, are also disclosed.

Solvent/polymer solutions as suspension vehicles

Osmotic drug delivery devices containing suspension formulations comprising particles having active agents and nonaqueous single-phase vehicles

In one aspect, the present invention is directed to an osmotic pump that automatically provides an ascending release rate of active agent as the osmotic pump functions in an environment of operation and may be designed for implantation within a desired animal or human subject. An osmotic pump according to the present invention includes a reservoir, a rate controlling membrane, an expandable osmotic composition, an active agent formulation and an exit orifice. Once administered to an environment of operation, water passes through the rate controlling membrane and into the osmotic composition, which causes the osmotic composition to expand and expel the active agent formulation through the exit orifice at a rate that is directly proportional to the rate at which water passes through the rate controlling membrane. An osmotic pump according to the present invention permits the flow of water through the rate controlling membrane to increase automatically without the need for manipulation of the osmotic pump after administration. As the flow of water through the rate controlling membrane increases, the rate at which active agent is delivered from the osmotic pump will also increase proportionally.

Osmotically driven active agent delivery device providing an ascending release profile

An osmotic delivery system has a membrane plug retention mechanism which can also be used to control the delivery rate of a beneficial agent from the osmotic delivery system. The osmotic delivery device includes an implant capsule containing a beneficial agent and an osmotic agent. Holes are formed along a side wall of the implant capsule at an open end of the capsule. When the membrane plug is inserted into the open end of the capsule, the membrane material swells into the holes in the capsule side wall creating a large frictional force which prevents expulsion of the membrane plug. A beneficial agent delivery rate of the osmotic delivery system is controllable by varying the size and number of the holes to change the amount of exposed surface area of the membrane plug. An increase in the surface area of the membrane plug exposed to the exterior environment causes a corresponding increase in the liquid permeation rate of the membrane and thus, increases the beneficial agent delivery rate.

Osmotic delivery system with membrane plug retention mechanism

Osmotic delivery system semipermeable body assemblies that control the delivery rate of a beneficial agent from an osmotic delivery system incorporating one of the semipermeable body assemblies are provided. A semipermeable body assembly or plug includes a semipermeable body which is positionable in an opening of an osmotic delivery system. The semipermeable body has a hollow interior portion having a size selected to obtain a predetermined liquid permeation rate through the semipermeable body. Because the beneficial agent in the osmotic delivery system is delivered at substantially the same rate, the osmotic agent imbibes liquid which has permeated through the plug from a surrounding environment, and the liquid permeation rate through the plug controls the delivery rate of the beneficial agent from the osmotic delivery system. The liquid permeation rate through a semipermeable body may be varied to control the delivery rate of beneficial agent from an osmotic delivery system by changing the thickness of the semipermeable body or by changing an amount of surface area of the semipermeable body that is exposed to liquid when the osmotic delivery system is located in a liquid environment of use.

Osmotic delivery system, osmotic delivery system semipermeable body assembly, and method for controlling delivery rate of beneficial agents from osmotic delivery systems

Osmotic delivery system semipermeable body assemblies that control the delivery rate of a beneficial agent from an osmotic delivery system incorporating one of the semipermeable body assemblies. A semipermeable body assembly or plug includes a semipermeable body which is positionable in an opening of an osmotic delivery system. The semipermeable body has a hollow interior portion having a size selected to obtain a predetermined liquid permeation rate through the semipermeable body. Because the beneficial agent in the osmotic delivery system is delivered at substantially the same rate the osmotic agent imbibes liquid which has permeated through the plug from a surrounding environment, the liquid permeation rate through the plug controls the delivery rate of the beneficial agent from the osmotic delivery system. The liquid permeation rate through a semipermeable body may be varied to control the delivery rate of beneficial agent from an osmotic delivery system by changing the thickness of the semipermeable body or by changing an amount of surface area of the semipermeable body that is exposed to liquid when the osmotic delivery system is located in a liquid environment of use.

Osmotic delivery system, osmotic delivery system semimpermeable body assembly, and method for controlling delivery rate of beneficial agents from osmotic delivery systems

Performance of delivery systems for delivering beneficial agents to an animal are monitored to determine the delivery rate of the beneficial agent and the proper operation of the beneficial agent delivery device. Performance monitoring can be achieved by monitoring the physical configuration of the implanted osmotic delivery device from the exterior of the body to determine the amount of beneficial agent delivered and/or the delivery rate of the beneficial agent. The monitoring of the physical configuration of the implanted osmotic delivery device may be performed in different manners such as by X-ray or fluoroscopic monitoring of the implant structure or magnetic determination of a piston location within the implant. Performance monitoring can also be achieved by use of a performance marker within the beneficial agent to produce a specifically detectable response which can be measured noninvasively in body fluids or by-products.

Osmotic drug delivery monitoring system and method

An osmotic delivery system has a membrane plug retention mechanism which can also be used to control the delivery rate of a beneficial agent from the osmotic delivery system. The osmotic delivery device includes an implant capsule containing a beneficial agent and an osmotic agent. Holes are formed along a side wall of the implant capsule at an open end of the capsule. When the membrane plug is inserted into the open end of the capsule the membrane material swells into the holes in the capsule side wall creating a large frictional force which prevents expulsion of the membrane plug. A beneficial agent delivery rate of the osmotic delivery system is controllable by varying the size and number of the holes to change the amount of exposed surface area of the membrane plug. An increase in the surface area of the membrane plug exposed to the exterior environment causes a corresponding increase in the liquid permeation rate of the membrane and thus, increases the beneficial agent delivery rate.

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Cupertino, CA, United States of America

Rupal A Ayer