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

• US 6,217,911 B1
• Filed: 07/05/1996
• Issued: 04/17/2001
• Est. Priority Date: 05/22/1995
• Status: Expired due to Fees

• Current Assignee: The United States of America As Represented By The Secretary of Agriculture
• Original Assignee: The United States Of America As Represented By The Secretary Of The Army
• Inventors: Vaugn, William M., Setterstrom, Jean A., Van Hamont, John E.
• Primary Examiner(s): Harrison, Robert H.
• Application Number:
  US08/675,895
• Time in Patent Office: 1,747 Days
• Field of Search: 424/501, 424/422, 424/423, 424/425, 424/426, 424/444, 424/484, 424/486, 424/489, 424/490, 424/497, 514/570, 514/626, 514/818, 514/887, 514/944, 514/953, 514/963, 514/965
• 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 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 mixture of uncapped biocompatible, biodegradable poly (lactide/glycolide) polymer and end-capped biocompatible, biodegradable poly (lactide/glycolide) polymer.

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

3. The microcapsule pharmaceutical formulation of claims 1 or 2, wherein said poly (lactide/glycolide) polymers have a molecular weight from 10-100 kDa.

4. The microcapsule pharmaceutical formula of claims 1 or 2 wherein the end-capped polymer comprises terminal residues functionalized as esters and said end-capped polymer is hydrophobic.

5. The microcapsule pharmaceutical formulation of claims 1 or 2 wherein the uncapped polymer comprises terminal residues existing as carboxylic acids and said uncapped polymer is hydrophilic.

6. The microcapsule pharmaceutical formula of claims 1 or 2 wherein the non-steroidal, antiinflammatory drug is selected from the group consisting of ibuprofen, florabioprofen, aspirin, acetaminophen, endocen, toridol, voltren, telecten, and ketoprofen.

7. The microcapsule pharmaceutical formulation of claim 6, wherein the non-steroidal, antiinflammatory drug is ketoprofen.

8. A dentistry pulp capping agent for treating pulping pain and pulpalgia inflammation comprising the controlled release microcapsule pharmaceutical formulation of claim 1.

9. An arthritis joint application for treating inflammation and pain comprising the controlled release microcapsule pharmaceutical formulation of claim 1.

10. The controlled release microcapsule pharmaceutical formulation of claim 1, wherein said antiinflammatory drug comprises 1-20% w/w ketoprofen.

11. The controlled release microcapsule pharmaceutical formulation of claim 1, wherein said drug is evenly distributed through the PLGA matrix.

12. The controlled release microcapsule pharmaceutical formulation of claim 1, wherein said drug and said polymers comprise a homogeneous solid matrix.

13. A topical treatment comprising the controlled release microcapsule pharmaceutical formulation of claim 1.

14. A bioadhesives or gel formulation to be used in wound or trauma sites comprising the controlled release microcapsule pharmaceutical formulation of claim 1.

15. The controlled release microcapsule pharmaceutical formulation of claim 6, wherein said microcapsules have narrow polydispersites and are smooth and non-porous.

22. The controlled release microcapsule pharmaceutical formulation of claim 10, wherein said microcapsules are smooth, spherical and porous.

16. A controlled release microcapsule pharmaceutical formulation for burst-free, sustained, programmable release of a long-acting anesthetic over a duration of from 7 to 10 days, comprising a long-acting local anesthetic agent and a blend of end-capped biodegradable poly(lactide/glycolide, polymer and uncapped biodegradable poly(lactide/glycolide) polymer.

17. The controlled release microcapsule pharmaceutical formulation of claim 16, wherein the localized anesthetic is selected from the group consisting of tetracaine, lidocaine, etidocaine, carobicaine, xylocaine, marcaine, nesacaine, and etiod.

18. The controlled release microcapsule pharmaceutical formulation of claim 17, wherein the long-acting local anesthetic is lidocaine.

19. The controlled release microcapsule pharmaceutical formulation of claim 18, wherein said microcapsules are loaded with 5% to 20% lidocaine.

20. The controlled release microcapsule pharmaceutical formulation of claim 18, wherein said microcapsules are from 120-135 μ

m in size.

21. The controlled release microcapsule pharmaceutical formulation of claim 18, wherein said microcapsules are from 7-10 μ

m in size.