PROCESS FOR PREPARING MICROPARTICLES

• US 20110172141A1
• Filed: 07/10/2009
• Published: 07/14/2011
• Est. Priority Date: 07/11/2008
• Status: Active Grant

• Current Assignee: Critical Pharmaceuticals Limited
• Original Assignee: Critical Pharmaceuticals Limited
• Inventors: Illum, Lisbeth, Lewis, Andrew Lester, Naylor, Andrew
• Granted Patent: US 9,226,900 B2
• Time in Patent Office: Days
• US Class Current: 514/1.1
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 38/385 Serum albumin
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/1682 Processes
• 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 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid

Abstract

A process for preparing microparticles comprising a biologically active material and a polymer and having a mean particle size expressed as the volume mean diameter (VMD) of from 10 to 500 μm, wherein the biologically active material is substantially insoluble in the polymer, which process comprises: a. contacting a mixture of the biologically active material or a precursor thereof, the polymer or a precursor thereof and a processing aid with a supercritical fluid which is capable of swelling the polymer under temperature and pressure conditions necessary to maintain the fluid in a supercritical state; b. allowing the supercritical fluid to penetrate and liquefy the polymer, whilst maintaining the temperature and pressure conditions so that the fluid is maintained in a supercritical state; c. releasing the pressure to precipitate microparticles comprising the biologically active agent and the polymer.

Claims

1. A process for preparing microparticles comprising a biologically active material and a polymer, said microparticles having a mean particle size expressed as the volume mean diameter (VMD) of from 10 to 500 μ

m, wherein the biologically active material is substantially insoluble in the polymer, which process comprises;

a) contacting a mixture of the biologically active material or a precursor thereof, the polymer or a precursor thereof and a processing aid with a supercritical fluid which is capable of swelling the polymer under temperature and pressure conditions necessary to maintain the fluid in a supercritical state;

b) allowing the supercritical fluid to penetrate and liquefy the polymer, whilst maintaining the temperature and pressure conditions so that the fluid is maintained in a supercritical state;

c) releasing the pressure to precipitate microparticles comprising the biologically active agent and the polymer.

2. A process according to claim 1, wherein the processing aid is selected from oligomers or polymers of fatty acids, fatty acid esters, hydroxy fatty acid esters, pyrolidones or polyethers, medium and long chain triglycerides, poloxamers, phospholipids, derivatives thereof and mixtures thereof.

3. A process according to claim 1, wherein the processing aid is an amphiphilic material having a hydrophilic-lipophilic balance of from about 1 to about 50.

4. A process according to claim 2, wherein the processing aid is a fatty acid ester.

5. A process according to claim 4, wherein the processing aid comprises polyglycol mono- and di-esters of 12-hydroxystearic acid.

6. A process according to claim 1, wherein the microparticles have a VMD of from about 40 to about 100 μ

m.

7. A process according to claim 6, wherein no more than 10% of the microparticles have a diameter (D_10%) less than 40 μ

m and at least 90% of the particles have a diameter (D_90%) of 100 μ

m or less.

8. A process according to claim 1, wherein the microparticles have a surface area which is from about 4(pi)r² to about 10,000×

4(pi)r², wherein r is half the VMD.

9. A process according to claim 8, wherein the microparticles have a surface area which is from about 4(pi)r² to about 1000×

4(pi)r², for example from about 4(pi)r² to about 10×

4(pi)r², wherein r is half the VMD.

10. A process according to claim 1, wherein the supercritical fluid is carbon dioxide.

17. A process or use according to claim 1, wherein the amount of the processing agent is from 0.2 to 30% by weight of the total weight of the biologically active material, the polymer and the processing aid.

18. Microparticles obtainable by a process according to claim 1.

19. A composition comprising microparticles obtainable by a process according to claim 1.

11. A process of increasing or enhancing the yield of microparticles comprising a biologically active material and a polymer comprising ontacting a mixture of a biologically active material or a precursor thereof, a polymer or a precursor thereof and a processing aid with a supercritical fluid which is capable of swelling the polymer under temperature and pressure conditions necessary to maintain the fluid in a supercritical state, wherein the biologically active material is substantially insoluble in the polymer.

12. The process according to claim 11, wherein the yield is increased by at least 100% as compared to the yield obtained using the same process in the absence of a processing aid.

13. A use according to claim 12, wherein the processing aid is selected from oligomers or polymers of fatty acids, fatty acid esters, hydroxy fatty acid esters, pyrolidones or polyethers, medium and long chain triglycerides, poloxamers, phospholipids, derivatives thereof and mixtures thereof.

14. A use according to claim 11, wherein the processing aid is an amphiphilic material having a hydrophilic-lipophilic balance of from about 1 to about 50.

15. A use according to claim 13, wherein the processing aid is a fatty acid ester.

16. A use according to claim 15, wherein the processing aid comprises polyglycol mono- and di-esters of 12-hydroxystearic acid.

20. A process or use according to claim 11, wherein the amount of the processing agent is from 0.2 to 30% by weight of the total weight of the biologically active material, the polymer and the processing aid.