Process for improving release kinetics of a monolithic drug delivery device

• US 3,923,939 A
• Filed: 06/07/1974
• Issued: 12/02/1975
• Est. Priority Date: 06/07/1974
• Status: Expired due to Term

• Current Assignee: Alan S. Michaels, Felix Theeuwes, Richard Baker
• Original Assignee: Alan S. Michaels, Felix Theeuwes, Richard Baker
• Inventors: Baker, Richard W., Michaels, Alan S., Theeuwes, Felix
• Primary Examiner(s): Anderson, Philip
• Application Number:
  US05/477,297
• Time in Patent Office: 543 Days
• Field of Search: 264/233,344,49,109 424/21,22
• US Class Current: 264/49
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0039 Devices retained in the uterus for a prolonged period, e.g. intrauterine devices for contraception
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system

Abstract

A process for improving the release kinetics of a monolithic active agent delivery device comprising a shaped body of a dispersion of particulate active agent, such as a drug, with a polymer matrix, such as ethylene/vinylacetate copolymer, by substantially reducing the initial burst of active agent from the device when it is placed in its environment of use. The process involves prior to placing the body in its use environment removing, such as by water washing, the particulate drug from the exterior surface of the body to form an agent depleted layer of polymer matrix voided by the removal of the agent, the thickness of the layer being at least 5% of the overall body thickness.

Claims

1. METHOD FOR SUBSTANTIALLY REDUCING THE INITIAL BURST OF ACTIVE AGENT RELEASE FROM A MONOLITHIC ACTIVE AGENT DELIVERY DEVICE WHEN SAID DEVICE IS PLACED IN ITS ENVIRONMENT OF USE, SAID DEVICE COMPRISING A SHAPED BODY OF A DISPERSION OF PARTICULATE ACTIVE AGENT WITHIN A POLYMER MATRIX COMPRISING PRIOR TO PLACING SAID SHAPED BODY IN SAID ENVIRONMENT, REMOVING THE PARTICULATE AGENT FROM THE EXTERIOR SURFACE OF SAID BODY TO FORM AN AGENT DEPLETED LAYER OF POLYMER MATRIX VOIDED BY SUCH REMOVAL OF PARTICULATE ACTIVE AGENT, THE THICKNESS OF SAID BEING AT LEAST ABOUT 5% OF THE OVERALL THICKNESS OF THE BODY.

2. The method of claim 1 wherein said removing is done by washing the body in a liquid which is inert relative to said polymer matrix.

3. The method of claim 2 wherein said liquid is water.

4. The method of claim 2 wherein said device is a diffusion type device and said washing is carried out at an elevated temperature at which diffusion of the agent from the matrix is enhanced.

5. The method of claim 2 wherein the polymer matrix is an ethylene/vinyl acetate copolymer and the washing is carried out at about 50*C to about 60*C.

6. The method of claim 2 wherein the device is an osmotic bursting type device and the washing is carried out at an elevated temperature at which imbibition of said liquid by the active agent is enhanced.

7. The method of claim 1 wherein the thickness of the layer is about 5% to 25% of the overall thickness of the body.

8. In a process for making a monolithic drug delivery device comprising a dispersion of solid particulate drug in a polymer matrix comprising the steps of forming a dispersion of the solid particulate drug within said matrix and forming the dispersion into a shaped body adapted for placement in the environment of use of the device, the improvement comprising the additional step of removing the solid particulate drug from the surface of said body to Form a drug depleted layer of polymer matrix voided by the removal of the particulate solid drug therefrom, the thickness of said layer being at least about 5% of the overall thickness of said body.

9. The improvement of claim 8 in which the thickness of said layer is about 5% to about 25% of the overall thickness of the body.

10. The improvement of claim 8 wherein said removing is done by washing the body in a liquid which is inert relative to the polymer matrix.

11. The improvement of claim 10 wherein the liquid is water.

12. The improvement of claim 10 wherein the device is a diffusion type device and said washing is carried out at an elevated temperature at which diffusion of the drug from the matrix is enhanced.

13. The improvement of claim 12 wherein the polymer matrix is made of an ethylene/vinyl acetate copolymer and the elevated temperature is from about 50*C to about 60*C.

14. The improvement of claim 10 wherein the device is an osmotic bursting type device and the washing is carried out at an elevated temperature at which the imbibition of liquid by the active agent is enhanced.