Sustained release non-steroidal, anti-inflammatory and lidocaine PLGA microspheres

• US 6,528,097 B1
• Filed: 11/20/2000
• Issued: 03/04/2003
• Est. Priority Date: 03/16/1984
• Status: Expired due to Fees

• Current Assignee: United States Army (U.S. Department Of Defense)
• Original Assignee: The United States Of America As Represented By The Secretary Of The Army
• Inventors: Setterstrom, Jean A., Van Hamont, John E., Vaughn, William M.
• Primary Examiner(s): Travers, Russell
• Assistant Examiner(s): Willis, Michael A.
• Application Number:
  US09/716,856
• Time in Patent Office: 834 Days
• Field of Search: 424/501, 424/422, 514/570
• US Class Current: 424/501
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Abstract

A controlled release microcapsule pharmaceutical formulation for burst-free, sustained, programmable release of a non-steroidal, antiinflammatory drug over a duration from 24 hours to 2 months, comprising: a non-steroidal, antiinflammatory drug and a blend of biocompatible, biodegradable poly (lactide/glycolide).

Claims

1. A process for preparing controlled release microcapsule formulations characterized by burst-free, sustained, programmable release of non-steroidal, antiinflammatory drugs comprising:

dissolving a non-steroidal, antiinflammatory drug and a mixture of uncapped biocompatible, biodegradable poly (lactide/glycolide) polymer and end-capped biocompatible, biodegradable poly (lactide/glycolide) polymer in a volatile organic solvent, dispersing the dissolved mixture in an aqueous phase containing an emulsion stabilizer, and evaporating the organic solvent phase to obtain non-steroidal antiinflammatory drug-loaded microspheres.

4. The process of claim 1, wherein the biodegradable poly (lactide/glycolide) polymers comprise a ratio of lactide to glycolide from 100/0 to 50/50.

5. The process of claim 1, wherein said poly (lactide/glycolide) polymers have a molecular weight from 10-100 kDa.

6. The process of claim 1, wherein the end-capped polymer comprises terminal residues functionalized as esters and said end-capped polymer is hydrophobic.

7. The process of claim 1, wherein the uncapped polymer comprises terminal residues existing as carboxylic acids and said uncapped polymer is hydrophilic.

8. The process of claim 1, wherein the non-steroidal, antiinflammatory drug is selected from the group consisting of ibuprofen, florabioprofen, aspirin, acetaminophen, endocen, toridol, voltren, telecten, and ketoprofen.

9. The process of claim 8, wherein the non-steroidal, antiinflammatory drug is ketoprofen.

10. The process of claim 1, wherein said drug is evenly distributed through the poly(lactide/glycolide) matrix.

11. The process of claim 1, wherein said drug and said polymers comprise a homogeneous solid matrix.

17. The process of claim 6, wherein the non-steroidal, antiinflammatory drug is ketoprofen.

2. A process for preparing controlled release microcapsule formulations characterized by burst-free, sustained, programmable release of non-steroidal, antiinflammatory drugs comprising:

dissolving a non-steroidal, antiinflammatory drug and a mixture of uncapped biocompatible, biodegradable poly (lactide/glycolide) polymer and end-capped biocompatible, biodegradable poly (lactide/glycolide) polymer in a polar organic solvent, dispersing the dissolved non-steroidal, antiinflammatory drug dissolved in a polar organic solvent in a non-polar organic phase, pouring the emulsion into a hydrocarbon solvent, extracting the polar organic phase into the hydrocarbon solvent to form microspheres.

12. The process of claim 2, wherein the biodegradable poly (lactide/glycolide) polymers comprise a ratio of lactide to glycolide from 100/0 to 50/50.

13. The process of claim 2, wherein said poly (lactide/glycolide) polymers have a molecular weight from 10-100 kDa.

14. The process of claim 2, wherein the end-capped polymer comprises terminal residues functionalized as esters and said end-capped polymer is hydrophobic.

15. The process of claim 2, wherein the uncapped polymer comprises terminal residues existing as carboxylic acids and said uncapped polymer is hydrophilic.

16. The process of claim 2, wherein the non-steroidal, antiinflammatory drug is selected from the group consisting of ibuprofen, florabioprofen, aspirin, acetaminophen, endocen, toridol, voltren, telecten, and ketoprofen.

18. The process of claim 2, wherein said drug is evenly distributed through the poly(lactide/glycolide) matrix.

19. The process of claim 2, wherein said drug and said polymers comprise a homogeneous solid matrix.

3. A process of preparing a controlled release microcapsule formulation characterized by burst-free sustained programmable release of a long-acting local anesthetic comprising:

dissolving the long-acting local anesthetic and a mixture of uncapped biocompatible, biodegradable poly(lactide/glycolide) polymer and end-capped biocompatible, biodegradable poly(lactide/glycolide) polymer in a volatile organic solvent, dispersing the long-acting local anesthetic and volatile organic solvent in an aqueous phase containing an emulsion stabilizer, and evaporating the volatile organic solvent to precipitate microspheres of long-lasting local anesthetic and poly(lactide/glycolide) microspheres.

20. The process of claim 3, wherein the local anesthetic is selected from the group consisting of tetracaine, lidocaine, etidocaine, carobicaine, xylocaine, marcaine, nesacaine, and etiod.

21. The process of claim 20, wherein the long-acting local anesthetic is lidocaine.