Method for fabricating polymer-based controlled-release devices

• US 6,183,781 B1
• Filed: 01/07/1997
• Issued: 02/06/2001
• Est. Priority Date: 05/14/1996
• Status: Expired due to Term

• Current Assignee: Alkermes Controlled Therapeutics Inc. II (Alkermes plc)
• Original Assignee: Alkermes Controlled Therapeutics Inc. II (Alkermes plc)
• Inventors: Burke, Paul A.
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US08/779,777
• Time in Patent Office: 1,491 Days
• Field of Search: 424/486, 424/426, 424/428, 424/499-501, 424/489, 428/402, 514/251-252, 264/5, 264/13, 264/140, 264/141
• US Class Current: 424/486
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient

Abstract

The present invention includes a method for producing an implantable polymer/drug matrix mass, comprising the steps of (1) forming a polymer solution/drug mixture comprising a polymer dissolved in an organic solvent and a suspended labile drug; (2) removing the solvent from the polymer solution/drug mixture, thereby forming a solid polymer/drug matrix; and (3) mechanically compressing the polymer/drug matrix, thereby forming an implantable polymer/drug matrix mass.

Claims

1. A method for preparing a polymer/drug matrix mass, wherein the drug is a labile drug, consisting essentially of the steps of:

(a) forming a polymer solution/drug mixture comprising a polymer dissolved in an organic solvent and a drug suspended in said solvent;

(b) removing the solvent from the polymer solution/drug mixture, thereby forming a solid polymer/drug matrix;

(c) fragmenting the solid polymer/drug matrix at a temperature below the glass transition temperature of the solid polymer/drug matrix, thereby forming polymer/drug matrix microparticles; and

(d) compressing the polymer/drug matrix microparticles to produce a polymer/drug matrix mass.

2. The method of claim 1 wherein the polymer is a bioerodable polymer.

3. The method of claim 1 wherein the solvent is removed from the polymer solution/drug mixture at a temperature below the freezing point of the polymer solution/drug mixture.

4. The method of claim 3 wherein the solvent is removed from the polymer solution/drug mixture by a method comprising the steps of:

(i) freezing the polymer solution/drug mixture, thereby forming a solid polymer solution/drug mixture; and

(ii) extracting the solvent from the solid polymer solution/drug mixture.

5. The method of claim 4 wherein the polymer solution/drug matrix is frozen by directing the polymer solution/drug mixture into a liquid nonsolvent, at a temperature below the freezing point of the polymer solution/drug mixture.

6. The method of claim 5 wherein the polymer solution/drug mixture is directed into the liquid nonsolvent by pouring, atomizing, spraying, extruding or dripping the polymer solution/drug mixture into the liquid nonsolvent.

7. The method of claim 4 wherein the polymer/drug matrix is frozen by directing the polymer solution/drug mixture onto a frozen nonsolvent bed in the presence of a liquified gas.

8. The method of claim 4 wherein the solvent is extracted from the polymer solution/drug mixture by contacting the solid polymer solution/drug mixture with a nonsolvent, thereby extracting the solvent into the nonsolvent.

9. The method of claim 4 wherein the solvent is extracted from the solid polymer solution/drug mixture by lyophilizing the solid polymer solution/drug mixture.

10. The method of claim 1 wherein the solvent is removed from the polymer solution/drug mixture by a method comprising the steps of:

(i) directing the polymer solution/drug mixture into a nonsolvent at a temperature suitable for precipitating the polymer/drug matrix, thereby forming a polymer/drug matrix-nonsolvent mixture; and

(ii) separating the nonsolvent and the polymer/drug matrix by filtering the polymer/drug matrix-nonsolvent mixture.

11. The method of claim 1 wherein step (d) is performed at a temperature at or below ambient temperature.