Sustained release formulation of a non-steroidal anti-inflammatory drug
View Patent ↗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.
1. A method of treating pain and inflammation, comprising administering a formulation comprising one or more non-steroidal anti-inflammatory drugs encapsulated in a first aqueous phase of multivesicular liposomes, to a subject in need thereof by injection, wherein the multivesicular liposomes comprise at least one anionic amphipathic phospholipid and at least one neutral lipid, wherein the one or more non-steroidal anti-inflammatory drugs are selected from the group consisting of meloxicam, piroxicam, and diclofenac, and wherein the total concentration of the non-steroidal anti-inflammatory drug in the multivesicular liposomes formulation is at least about 1.0 mg/mL.
2. The method of claim 1 , wherein the formulation further comprises a pharmaceutically acceptable carrier for injection.
3. The method of claim 1 , wherein the multivesicular liposomes comprise cholesterol, one or more phosphatidylglycerols, including salts of the phosphatidylglycerols, and one or more triglycerides.
4. The method of claim 1 , wherein the multivesicular liposomes comprise DPPG, DEPC, and tricaprylin.
5. The method of claim 1 , wherein the multivesicular liposomes comprise lysine.
6. The method of claim 1 , wherein the multivesicular liposomes comprise glutamic acid.
7. The method of claim 1 , wherein said administration is subcutaneous injection.
8. The method of claim 1 , wherein said administration is intramuscular injection.
9. The method of claim 1 , wherein said administration is intraarticular injection.
10. The method of claim 1 , wherein said administration comprises wound infiltration by local injection into a wound margin.
11. The method of claim 1 , wherein administration is every 1 to 7 days.
12. The method of claim 1 , wherein said non-steroidal anti-inflammatory drug is diclofenac.
13. The method of claim 1 , wherein said non-steroidal anti-inflammatory drug is meloxicam.
14. The method of claim 1 , wherein said multivesicular liposomes comprise a pH modifier selected from the group consisting of an inorganic acid, an inorganic base, an organic acid, an organic base, and a combination thereof.
15. The method of claim 1 , wherein said non-steroidal anti-inflammatory drug is piroxicam.
16. The method of claim 1 , wherein said multivesicular liposomes are characterized by an internal pH of about 8 to about 9.
17. The method of claim 1 , wherein said multivesicular liposomes comprise a pH modifier in the first aqueous phase selected from the group consisting of an organic acid, an organic base, and a combination thereof.
18. The method of claim 17 , wherein said multivesicular liposomes comprise an organic acid.
19. The method of claim 17 , wherein said multivesicular liposomes comprise an organic base.
20. The method of claim 1 , wherein said administration comprises instillation into a wound.