Production of microparticles

• US 20030180368A1
• Filed: 12/12/2002
• Published: 09/25/2003
• Est. Priority Date: 03/14/1998
• Status: Abandoned Application

• Current Assignee: Cenes Drug Delivery Limited
• Original Assignee: Cenes Drug Delivery Limited
• Inventors: Koppenhagen, Frank, Dawson, Gordon Findlay
• Application Number:
  US10/317,547
• Publication Number:
  US 20030180368A1
• Time in Patent Office: Days
• US Class Current: 424/490
• 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: C08J 3/09 in organic liquids
• CPC Class Codes: C08J 3/14 by precipitation from solutions C08J3/122 takes precedence

Abstract

A method of forming microparticles (especially including a pharmaceutically active agent) comprising incorporating an emulsifier in an aqueous liquid or in a non-aqueous solution (e.g. of dichloromethane) containing a polymer; forming a dispersion of the aqueous liquid in the non-aqueous solution; and agitating and adding a non-solvent (e.g. silicone oil) for the polymer. The presence of the emulsifier allows microparticle production over a wide range of conditions.

Claims

1. A method of producing microparticles, which comprises

incorporating an emulsifier in an aqueous liquid and/or a non-aqueous solution containing a polymer;

forming a dispersion of the aqueous liquid in the non-aqueous solution; and

agitating the dispersion and adding thereto a non-solvent for the polymer so as to form polymer microparticles.

2. A method according to claim 1 wherein the emulsifier is included in the aqueous liquid.

3. A method according to any preceding claim wherein the emulsifier is a non-ionic surfactant.

4. A method according to any preceding claim wherein the emulsifier is present in an amount of up to 60% by weight of the aqueous liquid or non-aqueous solution.

5. A method according to claim 4 wherein the emulsifier is present in an amount of up to 30% by weight.

6. A method according to any preceding claim wherein the emulsifier is present in the aqueous liquid or non-aqueous solution in an amount of at least 1% by weight.

7. A method according to any preceding claim wherein the emulsifier has an HLB value of 2 to 9.

8. A method according to any preceding claim wherein the aqueous liquid is from 5 to 50% by weight of the dispersion.

9. A method according to any preceding claim wherein the polymer is a polylactide-co-glycolide copolymer.

10. A method according to claim 9 wherein the ratio of lactide to glycolide is from 75:

25 to 50;

50 respectively.

11. A method according to any preceding claim wherein the polymer is present in the non-aqueous solution in an amount of 0.5 to 10% by weight.

12. A method according to any preceding claim wherein the non-aqueous solvent is dichloromethane.

13. A method according to any preceding claim wherein the non-solvent has a viscosity of less than 500 mPa.

14. A method according to claim 13 wherein the viscosity is 50-150 mPa.

15. A method according to any preceding claim wherein a pharmaceutically active agent is present in the aqueous liquid.

16. A method according to claim 15 wherein the active agent is a protein or peptide.

17. A method according to any preceding claim wherein the loading efficiency (as defined herein) is at least 60%.

18. A microparticle which comprises a pharmaceutically active agent, residual emulsifier and a pharmaceutically acceptable polymer.

19. A microparticle according to claim 18 wherein the residual emulsifier is present in an amount of up to 5% by weight.

20. A microparticle according to claim 18 or 19 which is substantially free of hydrophobic non-solvent.

21. A microparticle according to claim 18, 19 or 20 having a particle size of 10-300 microns.