Process for the production of microcapsules

• US 5,648,096 A
• Filed: 06/22/1994
• Issued: 07/15/1997
• Est. Priority Date: 10/26/1992
• Status: Expired due to Fees

• Current Assignee: Schwarz Pharma Ag (Schwarz Pharma)
• Original Assignee: Schwarz Pharma Ag (Schwarz Pharma)
• Inventors: Merkle, Hans Peter, Gander, Bruno
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): GRASER, JENNIFER E
• Application Number:
  US08/264,007
• Time in Patent Office: 1,119 Days
• Field of Search: 424/489, 424/491, 424/499, 424/457, 424/490, 424/492-498, 424/500, 424/502, 430/138
• US Class Current: 424/489
• 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: A61K 9/5089 Processes
• CPC Class Codes: B01J 13/043 Drying and spraying

Abstract

A method for the production of microcapsules embedded with pharmaceuticals, peptides, proteins, enzymes and vaccines, which uses biodegradable solvents, and microcapsules free of toxic residual solvents is described. The microcapsules are obtained by spraying of a solution, suspension or water-in-oil dispersion of active materials and biodegradable polymers.

Claims

1. A method of manufacturing microcapsules containing one or more biodegradable polymers and at least one active material, which method comprises:

(a) dissolving the biodegradable polymer(s) in a non-toxic biodegradable solvent which is selected from esters of a C₁ -C₅ -alcohol and a C₁ -C₅ -monocarboxylic acid;

(b) incorporating at least one active material into the solution of the biodegradable polymer(s) obtained in step (a) either in the form of a solution of said active material in said biodegradable solvent;

or in the form of a micronized powder of said active material, or in the form of a solution of said active material in an aqueous medium, and

(c) spray drying the solution, suspension or water-in-oil dispersion obtained in step (b).

2. The method of claim 1, wherein the biodegradable solvent is ethyl formate.

3. The method of claim 1, wherein the biodegradable solvent is ethyl acetate.

4. The method of claim 1, wherein the biodegradable solvent is isopropyl acetate.

5. The method of claim 1, wherein the active material is a biologically active substance.

6. The method of claim 1, wherein the biologically active substance is a pharmaceutical, a peptide, a protein, an enzyme or a vaccine.

7. The method of claim 5, wherein the biologically active substance is a pharmaceutical, a vaccine or an enzyme.

8. A microcapsule containing one or more biodegradable polymers and a biologically active substance as prepared by the method of claim 1.

9. The microcapsule of claim 8, wherein the biologically active substance is selected from a pharmaceutical, a peptide, a protein, an enzyme and a vaccine.

10. The microcapsule of claim 9, wherein the biologically active substance is a pharmaceutical, a vaccine or an enzyme.

11. A method of manufacturing microcapsules comprising:

(a) dissolving one or more biodegradable polymers in a non-toxic biodegradable solvent which is selected from esters of a C₁ -C₅ -alcohol and a C₁ -C₅ -monocarboxylic acid to form a first solution;

(b) dissolving an active material in a non-toxic biodegradable solvent which is selected from esters of a C₁ -C₅ -alcohol and a C₁ -C₅ -monocarboxylic acid to form a second solution;

(c) combining the first solution with the second solution to obtain a substrate solution and,

(d) spray drying the substrate solution.

12. The method of claim 11, wherein the biodegradable solvent is ethyl formate.

13. The method of claim 11, wherein the biodegradable solvent is ethyl acetate.

14. The method of claim 11, wherein the biodegradable solvent is isopropyl acetate.

15. A method of manufacturing microcapsules comprising:

(a) dissolving one or more biodegradable polymers in a non-toxic biodegradable solvent which is selected from esters of a C₁ -C₅ -alcohol and a C.sub. -C₅ -monocarboxylic acid to form a polymer solution;

(b) suspending an active material mechanically or by means of ultrasound in the polymer solution to obtain a substrate suspension, and

(c) spray drying the substrate suspension.

16. The method of claim 15, wherein the biodegradable solvent is ethyl formate.

17. The method of claim 15, wherein the biodegradable solvent is ethyl acetate.

18. The method of claim 15, wherein the biodegradable solvent is isopropyl acetate.

19. The method of claim 15, wherein the active material is in micronized form.

20. A method of manufacturing microcapsules comprising:

(a) dissolving one or more biodegradable polymers in a non-toxic biodegradable solvent which is selected from esters of a C₁ -C₅ -alcohol and a C₁ -C₅ -monocarboxylic acid to form a polymer solution;

(b) dissolving an active material in an aqueous medium to form an aqueous active material solution;

(c) mixing the aqueous active material solution with the polymer solution mechanically or with ultrasound to obtain substrate water-in-oil dispersion, and

(d) spray drying the substrate water-in-oil dispersion.

21. The method of claim 20, wherein the biodegradable solvent is ethyl formate.

22. The method of claim 20, wherein the biodegradable solvent is ethyl acetate.

23. The method of claim 20, wherein the biodegradable solvent is isopropyl acetate.

24. The method of claim 20, wherein the dispersion in step (c) is obtained with ultrasound.