Process for preparation of microspheres

• US 4,384,975 A
• Filed: 06/13/1980
• Issued: 05/24/1983
• Est. Priority Date: 06/13/1980
• Status: Expired due to Term

• Current Assignee: Sadoz Incorporated
• Original Assignee: Sandoz Inc. (Novartis Ag)
• Inventors: Fong, Jones W.
• Primary Examiner(s): Lovering, Richard D.
• Application Number:
  US06/159,148
• Time in Patent Office: 1,075 Days
• Field of Search: 252/316, 424/33, 424/35, 424/19, 424/22
• US Class Current: 427/213.36
• 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: B01J 13/125 by evaporation of the solvent apparatus therefor B01J13/043

Abstract

Microspheres, prepared by solvent removal from an oil-in-water emulsion using carboxylic acid salt surfactant, e.g., sodium oleate as the emulsifier.

Claims

1. A process for the preparation of microspheres having a particulate core material encapsulated by a polymer coating which comprises, dissolving the polymer in a volatile, water-immiscible solvent in which the core material is not soluble, adding the core material particles, mixing the resulting dispersion with an aqueous solution containing sodium oleate or potassium oleate as an emulsifier to form an oil-in-water emulsion, and removing the solvent to form discrete microcapsules free of agglomerates.

2. The process according to claim 1 wherein the polymer is a biodegradable polymer.

3. The process according to claim 2 wherein the biodegradable polymer is polylactic acid, polyglycolic acid, polyhydroxybutyric acid, polycaprolactone, polyalkylene oxalate, or a polyalkylene glycol ester of acids of the citric acid cycle or copolymers thereof.

4. The process according to claim 3 wherein the polymer is polylactic acid.

5. The process according to claim 4 wherein the core material is selected from the group consisting of thioridazine, bromocriptine, a mixture of dihydroergocornine, dihydroergocristine, and dihydroergokryptine, and acid addition salts thereof.

6. The process according to claim 1 wherein the core material is a drug.

7. The process according to claim 6 wherein the polymer is a biodegradable polymer.

8. The process according to claim 1 wherein the polymer is selected from the group consisting of cellulosic polymers, polyvinylacetate, natural or synthetic rubbers, polyvinyl chloride, polyacrylates, and polystyrene.

9. A process for the preparation of microspheres having homogeneous mixture of a polymer and core material which comprises, dissolving the polymer and core material in a volatile, water-immiscible solvent, mixing the polymer-core material-solvent system with an aqueous solution containing sodium oleate or potassium oleate as an emulsifier to form an oil-in-water emulsion, and removing the solvent to form discrete microprills free of agglomerates.

10. The process, according to claim 9 wherein the polymer is a biodegradable polymer.

11. The process according to claim 10 wherein the biodegradable polymer is polylactic acid, polyglycolic acid, polyhydroxybutyric acid, polycaprolactone, polyalkylene oxalate, or a polyalkylene glycol ester of acids of the citric acid cycle or copolymers thereof.

12. The process according to claim 11 wherein the polymer is polylactic acid.

13. The process according to claim 12 wherein the core material is selected from the group consisting of thioridazine, bromocriptine, a mixture of dihydroergocornine, dihydroergocristine, and dihydroergokryptine, and acid addition salts thereof.

14. The process according to claim 9 wherein the core material is a drug.

15. The process according to claim 14 wherein the polymer is a biodegradable polymer.

16. The process according to claim 9 wherein the polymer is selected from the group consisting of cellulosic polymers, polyvinylacetate, natural or synthetic rubbers, polyvinyl chloride, polyacrylates, and polystyrene.