Microencapsulation of drugs by solvent exchange

• US 20020160109A1
• Filed: 12/13/2001
• Published: 10/31/2002
• Est. Priority Date: 12/13/2000
• Status: Active Grant

• Current Assignee: Purdue Research Foundation (Purdue University)
• Original Assignee: Purdue Research Foundation (Purdue University)
• Inventors: Chen, Alvin Un-Teh, Park, Kinam, Yeo, Yoon, Basaran, Osman A.
• Granted Patent: US 6,599,627 B2
• Time in Patent Office: Days
• US Class Current: 427/213.3
• 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: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: B01J 13/046 combined with gelification or coagulation
• CPC Class Codes: Y10T 428/2984 Microcapsule with fluid core [includes liposome]
• CPC Class Codes: Y10T 428/2985 Solid-walled microcapsule from synthetic polymer
• CPC Class Codes: Y10T 428/2991 Coated

Abstract

A solvent exchange method is employed to provide microencapsulated compositions, such as microcapsules of pharmaceutical preparations. The method is based on an exchange of water and a hydrophilic organic solvent, whereby a decline in solvent quality for the organic solvent causes a polymer dissolved therein to be deposited onto an aqueous core. Optimal results are rationalized in terms of a balance of water solubility and surface tension for the organic solvent. In a preferred embodiment, microcapsules of selected drugs are formed by contacting microdroplets of an aqueous solution containing the drug with the organic solvent containing a polymer dissolved therein. A preferred method employs biodegradable poly(lactic acid-co-glycolic acid) (PLGA) dissolved in acetic acid, ethyl acetate, methyl acetate, or ethyl formate, to form a PLGA membrane around an aqueous drug core. The method is particularly attractive for encapsulating protein-based drugs without substantial denaturation.

Claims

1. A method for preparing an encapsulated composition, comprising:

providing an aqueous solution composed of water and a core substance dissolved therein;

providing a polymer solution composed of a water-miscible solvent and a water-insoluble polymer dissolved therein;

forming a droplet of the aqueous solution containing the core substance; and

admixing the droplet of aqueous solution with at least a portion of the polymer solution under conditions permitting the water-insoluble polymer to deposit as at least one layer on the core substance, thereby affording the encapsulated composition.

2. The method of claim 1, wherein the core substance is a physiologically active substance and the encapsulated composition exhibits controlled release properties.

3. The method of claim 2, wherein the core substance is a protein, oligonucleotide, gene, or polysaccharide.

4. The method of claim 3, wherein the core substance is a protein.

5. The method of claim 1, wherein the water-insoluble polymer is biocompatible.

6. The method of claim 5, wherein the polymer is biodegradable.

7. The method of claim 6, wherein the biodegradable polymer is a homopolymer of lactic acid or glycolic acid or a copolymer of lactic acid and glycolic acid.

8. The method of claim 1, wherein the water-miscible solvent is selected from the group consisting of acetic acid, ethyl acetate, methyl acetate and ethyl formate.

9. The method of claim 1, 2, 3, 4, or 6, wherein said droplet forming is performed with at least one syringe, single nozzle, coaxial nozzle, or microdispenser device.

10. The method of claim 1, 2, 3, 4, or 6, wherein said admixing is performed by contacting the droplet of aqueous solution with polymer solution using a coaxial nozzle device.

11. The method of claim 1, 2, 3, 4, or 6, wherein the droplet of aqueous solution is provided with an aqueous protecting layer.

12. The method of claim 1, 2, 3, 4, or 6, wherein said admixing is performed by combining the droplet of aqueous solution with a droplet of the polymer solution to afford a microparticle having an aqueous core and an outer polymer layer.

13. The method of claim 12, further comprising introducing the microparticle into water.

14. The method of claim 1, wherein the water-miscible solvent has a solubility parameter in the range of 16 to 26 MPa^½

.

15. The method of claim 1, wherein the water-miscible solvent has a surface tension of less than about 45 mN/m.

16. The method of claim 1, wherein the water-miscible solvent has a water solubility of 5 to 100%.

17. An encapsulated composition made by the method of claim 1, 2, 3, 4 or 6.