Sustained release formulation of a non-steroidal anti-inflammatory drug

Patent metadata

Field	Value
Publication number	US-10123974-B2
Application number	US-201313787462-A
Country	US
Kind code	B2
Filing date	Mar 6, 2013
Priority date	Oct 28, 2010
Publication date	Nov 13, 2018
Grant date	Nov 13, 2018

Abstract

Disclosed are formulations comprising multivesicular liposomes and one or more non-steroidal anti-inflammatory drugs which minimize the side effects of unencapsulated non-steroidal anti-inflammatory drugs while maintaining or improving efficacy. Methods of making and administering the formulations comprising multivesicular liposomes and one or more non-steroidal anti-inflammatory drugs and their use as medicaments are also provided.

First claim

What is claimed is:

1. A method of treating pain and inflammation for an extended period of time by wound infiltration, comprising administering a multivesicular liposome (MVL) formulation by local injection into a wound margin, or instillation into an incision wound, or a combination thereof, wherein the formulation comprises:
meloxicam; and
multivesicular liposomes, said multivesicular liposomes comprise at least one amphipathic phospholipid and at least one neutral lipid,
wherein said meloxicam is encapsulated in a first aqueous phase of the multivesicular liposomes, wherein the first aqueous phase comprises a pH modifier; and
wherein the multivesicular liposomes are characterized by an internal pH of about 8 to about 9.

2. The method of claim 1 , wherein the multivesicular liposomes comprise cholesterol, one or more phosphatidyl glycerols or salts thereof, one or more phosphatidyl cholines or salts thereof, and one or more triglycerides.

3. The method of claim 2 , wherein the phosphatidyl glycerols comprise DPPG.

4. The method of claim 2 , wherein the phosphatidyl cholines comprise DEPC.

5. The method of claim 2 , wherein the triglyceride is selected from triolein, tricaprylin, or a combination of the two.

6. The method of claim 1 , wherein the pH modifier comprises lysine or glutamic acid, or a combination thereof.

7. The method of claim 1 , wherein the pH modifier comprises an inorganic acid.

8. The method of claim 1 , wherein the pH modifier comprises an organic base.

9. The method of claim 1 , wherein the pH modifier comprises an inorganic base.

10. The method of claim 1 , wherein the multivesicular liposomes further comprise a cyclodextrin.

11. The method of claim 10 , wherein the cyclodextrin is in a concentration of from about 10 mg/ml to about 400 mg/ml complexed with meloxicam within the multivesicular liposomes.

12. The method of claim 10 , wherein said cyclodextrin is selected from the group consisting of (2,6-Di-O-)ethyl-β-cyclodextrin, (2-Carboxyethyl)-β-cyclodextrin sodium salt, (2-hydroxyethyl)-β-cyclodextrin, (2-hydroxypropyl)-α-cyclodextrin, sulfobutylether-β-cyclodextrin, (2-hydroxypropyl)-β-cyclodextrin, 6-monodeoxy-6-monoamino-β-cyclodextrin, 6-O-α-maltosyl-β-cyclodextrin, butyl-β-cyclodextrin, butyl-γ-cyclodextrin, carboxymethyl-β-cyclodextrin, methyl-β-cyclodextrin, succinyl-α-cyclodextrin, succinyl-β-cyclodextrin, triacetyl-β-cyclodextrin, α-cyclodextrin β-cyclodextrin, and γ-cyclodextrin.

13. The method of claim 1 , wherein the pH modifier comprises an organic acid.

14. The method of claim 1 , wherein the formulation is configured for administration at an interval of about 1 to about 7 days.

Assignees

• Pacira Pharmaceuticals Inc

Inventors

• Garcia Louie Daniel
• Zhu Liangjin
• Lambert William Joseph
• Patou Gary

Classifications

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61K31/5415

  ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam · CPC title

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61K9/1278

  Post-loading, e.g. by ion or pH gradient · CPC title