Composite core coated microparticles and process of preparing same

• US 4,568,559 A
• Filed: 02/06/1984
• Issued: 02/04/1986
• Est. Priority Date: 02/06/1984
• Status: Expired due to Term

• Current Assignee: BioTex Incorporated
• Original Assignee: BioTex Incorporated
• Inventors: Nuwayser, Elie S., Nucefora, William A.
• Primary Examiner(s): Kittle, John E.
• Assistant Examiner(s): Shah, Mukund J.
• Application Number:
  US06/577,079
• Time in Patent Office: 729 Days
• Field of Search: 424/31, 424/35, 428/402.24, 427/213, 427/3
• US Class Current: 427/2.15
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: Y10T 428/2989 Microcapsule with solid core [includes liposome]

Abstract

A process for preparing coated microparticles, which process comprises preparing a solvent solution of an active ingredient to be encapsulated and a film-forming polymer, removing the solvent to provide a dry, composite, uniform admixture of the active ingredient and the polymer material, reducing the composite admixture to a defined smaller particle size distribution, coating the reduced composite core particles in a fluidized bed, with a uniform defined wall thickness of the same or substantially the same film-forming polymer material to provide composite core coated microparticles.

Claims

1. A process for preparing coated microparticles, which process comprises:

(a) preparing a solid, dry, composite admixture of a uniform dispersion of an active ingredient to be coated and a film-forming polymer;

(b) reducing the dry, composite admixture to provide composite core particles of defined particle size distribution of less than 1000 microns and selecting the reduced composite core particles the size distribution of which particles is the same or slightly less than the particle size distribution of the desired coated microparticles to be prepared;

(c) coating the reduced selected composite core particles in a fluidized bed with a uniform defined wall thickness of the same or substantially the same film-forming polymer material employed in preparing the composite core materials; and

(d) recovering the coated microparticles of the desired size distribution range.

2. The process of claim 1 wherein the film-forming material comprises a polymeric material selected from the group consisting of a biodegradable polymer, polyvinyl alcohol, and cellulose material.

3. The process of claim 2 wherein the film-forming material comprises a polylactide, a polyglycolide, and copolymers of lactide and glycolide.

4. The process of claim 1 wherein the active ingredient comprises a hydrophobic drug.

5. The process of claim 4 wherein the active material comprises a hydrophobic steroid.

6. The process of claim 1 wherein the active ingredient comprises levonorgestrel as the active ingredient and wherein the film-forming polymer comprises a polylactide, a polyglycolide, or copolymers of lactide and glycolide.

7. The process of claim 1 wherein the active ingredients in the composite core material ranges from about 5 to 95% by weight of the composite core material.

8. The process of claim 1 wherein the active ingredient comprises from about 60 to 90% by weight of the composite core material.

9. The process of claim 1 which comprises selecting the reduced composite core material having a particle size of less than about 200 microns.

10. The process of claim 1 wherein the preparing of the solid, dry, composite admixture includes preparing a volatile organic solution of the active ingredient and the film-forming polymer, and removing the solvent to provide a dry, composite, uniform admixture of the active ingredient in the film-forming polymer material.

11. The process of claim 1 which includes washing of the reduced composite core particles to remove substantially fines prior to selecting the reduced composite cores particles.

12. The process of claim 1 which includes coating the reduced composite core particle with a uniform wall coating of about 0.1 to 20 microns.

13. The process of claim 1 wherein the covered coated microparticles have a particle size of less than about 200 microns.

14. A process for preparing coated microparticles, which process comprises:

(a) preparing a solvent solution of an active drug ingredient and a organic, film-forming polymer material, the active drug ingredient present in an amount of from about 5 to 95% by weight and which is desired to be released at a controlled-release rate from the coated microparticles;

(b) removing the solvent to provide a dry, composite, generally-uniform admixture of the drug-active ingredient and the biodegradable, organic, film-forming polymer material;

(c) reducing the dry, composite admixture by grinding to provide composite core particles of a defined particle size distribution of less than about 1000 microns;

(d) selecting from the reduced composite core material a particle size distribution, the same as or slightly less than the particle size distribution of the desired coated microparticles to be prepared;

(e) coating the reduced, selected, composite core microparticle in a fluidized bed drying process by spraying a solvent solution of the biodegradable organic film-forming polymer material into the fluidized bed of the composite core material particles to provide microparticles; and

(f) recovering and selecting from the coated recovered microparticles, coated microparticles of the desired particle size range.

16. The process of claim 14 wherein the active ingredient is selected from the group consisting of testosterone, progesterone, nonoxynol-9, povidone iodine, cholesterol, levonorgestrel, tyrosine, norethindrone, lidocaine, etidocaine and bupivacaine.

15. The process of claim 15 wherein the film-forming polymer comprises a polylactide, a polyglycolide, or a copolymer of the lactide and glycolide.

17. A process for preparing coated microparticles, which process comprises:

(a) preparing a solid, dry, composite admixture of the uniform dispersion of an active drug ingredient, which active ingredient is desired to be released at a controlled-release rate and which active ingredient is present in an amount that provides for such controlled-release rate and a biodegradable, organic, polymeric material, which material comprises a polylactide, a polyglycolide, or copolymers of lactide and glycolide;

(b) reducing the dry, composite admixture to provide composite core particles of defined particle size distribution, selecting the reduced composite core particles containing the active ingredient ranging from about 5 to 95% by weight of the composite core material, the size distribution of which particles is about 200 microns or less and is the same or slightly less than the particle size distribution of the desired coated microparticles to be prepared;

(c) coating the reduced selected composite core particles in a fluidized bed dryer with a uniform defined wall thickness of the same film-forming polymer material employed in preparing the composite core materials; and

(d) recovering the coated microparticles or the desired size distribution range.