Methods for fabricating polymer-based controlled release devices

• US 5,989,463 A
• Filed: 09/24/1997
• Issued: 11/23/1999
• Est. Priority Date: 09/24/1997
• Status: Expired due to Fees

• Current Assignee: Alkermes Controlled Therapeutics Inc. II (Alkermes plc)
• Original Assignee: Alkermes Controlled Therapeutics Inc. II (Alkermes plc)
• Inventors: Tracy, Mark A., Burke, Paul A., Herbert, Paul F., Herberger, John D.
• Primary Examiner(s): Nutter, Nathan M.
• Application Number:
  US08/935,452
• Time in Patent Office: 790 Days
• Field of Search: 264/4.1, 604/890.1, 424/484, 424/486, 424/489, 514/2, 514/21
• US Class Current: 264/4.1
• CPC Class Codes: A61K 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: Y10T 428/2985 Solid-walled microcapsule from synthetic polymer

Abstract

The present invention relates to a polymer-based sustained release device, and methods of forming and using the device for the sustained release of an active agent. The improved method of the invention for forming a polymer-bases sustained release device comprises forming a polymer/active agent solution by mixing a polymer, a continuous phase, and an active agent. The continuous phase can comprise one or more polymer solvents, a polymer solvent/polymer non-solvent mixture, or a polymer solvent/active agent non-solvent mixture. When the continuous phase comprises a polymer solvent/active agent non-solvent, the active agent can also be present as a microparticulate rather than in solution. The continuous phase is then removed from the polymer/active agent solution, thereby forming a solid polymer/active agent matrix.

Claims

1. A method of forming a polymer-based sustained release device comprising the steps of:

a) forming a polymer/biologically active agent solution by mixing a polymer, a continuous phase comprising one or more polymer solvents and a biologically active agent wherein the polymer and biologically active agent are present in relative concentrations such that the device contains about 50% by weight or more of the biologically active agent; and

b) removing the continuous phase of step (a) thereby forming a solid polymer/biologically active agent matrix.

2. The method of claim 1 wherein the continuous phase comprises DMSO.

3. The method of claim 1 wherein the biologically active agent is a peptide or an antigen.

4. The method of claim 1 wherein the biologically active agent is an LHRH analog.

5. The method of claim 1 wherein the biologically active agent is azaline B.

6. The method of claim 1 wherein the polymer is selected from the group consisting of:

poly(lactide)s, poly(glycolide)s, poly(lactide-co-glycolide)s, poly(lactic acid)s, poly(glycolic acid)s, poly(lactic acid-co-glycolic acid)s, blends thereof, and copolymers thereof.

7. A method for forming a polymer-based sustained release device comprising the steps of:

a) forming a polymer/biologically active agent solution by mixing a polymer, a continuous phase comprising one or more polymer solvents and a biologically active agent wherein the polymer and biologically active agent are present in relative concentrations such that the device contains about 50% by weight or more of the biologically active agent;

b) forming droplets of the polymer/biologically active agent solution; and

c) removing the continuous phase of step (a) from the polymer/biologically active agent solution thereby forming a solid polymer/biologically active agent matrix.

8. The method of claim 7 wherein the continuous phase comprises DMSO.

9. The method of claim 8 further comprising the step of freezing the droplets of the polymer/active agent solution prior to removing the continuous phase wherein the continuous phsae is removed by extraction.

10. The method of claim 7 wherein the continuous phase is removed by evaporation.

11. The method of claim 7 wherein the droplets are microdroplets.

12. The method of claim 7 wherein the biologically active agent is a peptide or an antigen.

13. The method of claim 7 wherein the biologically active agent is an LHRH analog.

14. The method of claim 7 wherein the biologically active agent is azaline B.

15. The method of claim 7 wherein the polymer is selected from the group consisting of:

poly(laclide)s, poly(glycolide)s, poly(lactide-co-glycolidc)s, poly(lactic acid)s, poly(glycolic acid)s, poly(lactic acid-co-glycolic acid)s, blends thereof, and copolymers thereof.