Injectable, long-acting microparticle formulation for the delivery of anti-inflammatory agents

• US 4,530,840 A
• Filed: 07/29/1982
• Issued: 07/23/1985
• Est. Priority Date: 07/29/1982
• Status: Expired due to Term

• Current Assignee: Alkermes Controlled Therapeutics Inc. II (Alkermes plc), Southwest Research Institute
• Original Assignee: Southwest Research Institute, Stolle Research & Development Corporation
• Inventors: Tice, Thomas R., Cowsar, Donald R., Lewis, Danny H., Beck, Lee R.
• Primary Examiner(s): Roberts, Elbert L.
• Application Number:
  US06/402,857
• Time in Patent Office: 1,090 Days
• Field of Search: 424/238, 424/241, 424/243, 424/31, 424/32
• US Class Current: 514/179
• 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: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

An anti-inflammatory agent containing microparticle composition prepared by a process, comprising (a) dissolving or dispersing an anti-inflammatory agent in a solvent and dissolving a biocompatible and biodegradable wall forming material in said solvent; (b) dispersing said solvent containing said anti-inflammatory agent and wall forming material in a continuous phase processing medium; (c) evaporating a portion of said solvent from said dispersion of step (b), thereby forming microparticles containing said anti-inflammatory agent in the suspension; and (d) extracting the remainder of the solvent from said microcapsules.

Claims

1. An anti-inflammatory agent containing microparticle composition prepared by a process, comprising:

(a) dissolving or dispersing an anti-inflammatory agent selected from the group consisting of a prednisolone, a triamicinolone, a dexamethasone and a β

-methasone in a solvent selected from the group consisting of acetone, a halogenated hydrocarbon, an aromatic hydrocarbon. a halogenated aromatic hydracarbon, a cyclic ether, an alcohol and water and dissolving a biocompatible and biodegradable wall forming material in said solvent;

(b) dispersing said solvent containing said anti-inflammatory agent and wall forming material in a continuous phase processing medium of water, toluene, xylene, a synthetic oil or a natural oil;

(c) evaporating a portion of said solvent from said dispersion of step (b), thereby forming microparticles containing said anti-inflammatory agent in the suspension; and

(d) extracting the remainder of the solvent from said microparticles.

2. The composition of claim 1, wherein the polymeric matrix material of said microparticles is poly-d, 1-lactic acid, polyglycolic acid, copolymers of mixed d,1-lactic acid and glycolic acid, copolyoxalates, polycaprolactone, or poly (lactic acid-caprolactone).

3. The composition of claim 1, wherein said microparticles are loaded with 1 to 75 wt. % of said anti-inflammatory agent based on said polymeric matrix.

4. The composition of claim 1, wherein said microparticles range in size from 1 to 200 microns.

5. The composition of claim 1, wherein said microparticles are formulated in a liquid injectable vehicle.

6. A method of treating inflammation comprising:

administering microparticles of claim 1 containing a pharmaceutically effective amount of an anti-inflammatory compound in a biocompatible and biodegradable matrix material to a subject.

7. The method of claim 6, wherein said microparticles are formed of a matrix of polymeric d,1-lactic acid, glycolic acid, copolymers thereof, copolyoxalates, polycaprolactone or poly (lactic acid-caprolactone).

8. The method of claim 6, wherein from microgram to milligram quantities of said corticosteroid are administered per day to a subject.

9. The method of claim 6, wherein said microparticles are administered by injection into the area of the inflammed joints of an affected subject.

10. The method of claim 6, wherein said injectable microparticles are formulated as microparticles in a liquid vehicle.

11. The method of claim 10, wherein said liquid vehicle is physiological saline solution.

12. The method of claim 6, wherein said micro-particles are administered by intra-muscular injection.