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

1. A process for preparing multivesicular liposomal formulations, the process comprising:

providing a first emulsion comprising at least one non-steroidal anti-inflammatory drug selected from the group consisting of piroxicam, and meloxicam by mixing a first aqueous phase comprising the at least one non-steroidal anti-inflammatory drug and one or more pH modifiers and a volatile water-immiscible solvent phase, wherein said solvent phase comprises at least one amphipathic lipid and at least one neutral lipid;

mixing and emulsifying said first emulsion and a second aqueous phase to provide a second emulsion, said second emulsion comprising a continuous aqueous phase; and

removing the volatile water-immiscible solvent from the second emulsion to form a composition of multivesicular liposomal particles encapsulating at least one non-steroidal anti-inflammatory drug in the first aqueous phase, wherein the multivesicular liposomes are characterized by an internal pH of about 7 or higher.

2. The process of claim 1 , wherein the multivesicular liposomes further comprise a pH modifier in the second aqueous phase.

3. The process of claim 1 , wherein the pH modifier of the first aqueous phase comprises lysine or glutamic acid, or a combination thereof.

4. The process of claim 1 , wherein the pH modifier of the first aqueous phase comprises an inorganic acid.

5. The process of claim 1 , wherein the pH modifier of the first aqueous phase comprises an organic base.

6. The process of claim 1 , wherein the pH modifier of the first aqueous phase comprises an inorganic base.

7. The process of claim 1 , wherein the non-steroidal anti-inflammatory drug is piroxicam.

8. The process of claim 1 , wherein the non-steroidal anti-inflammatory drug is meloxicam.

9. The process of claim 1 , wherein the pH modifier of the first aqueous phase comprises an organic acid.

10. The process of claim 1 , wherein at least one amphipathic lipid is selected from zwitterionic phospholipids, anionic amphipathic phospholipids, cationic amphipathic lipids, or combinations thereof.

11. The process of claim 1 , wherein at least one amphipathic lipid is selected from phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, lysophosphatidylcholines, lysophosphatidylethanolamines, or combinations thereof.

12. The process of claim 1 , wherein at least one amphipathic lipid is selected from phosphatidylglycerols, phosphatidylserines, phosphatidylinositols, phosphatidic acids, cardiolipins, or combinations thereof.

13. The process of claim 1 , wherein at least one amphipathic lipid is selected from acyl trimethylammonium propanes, diacyl dimethylammonium propanes, stearylamine, or combinations thereof.

14. The process of claim 1 , wherein at least one amphipathic lipid is selected from dioleyl phosphatidyl choline (DOPC), dierucoyl phosphatidylcholine or 1,2-dierucoyl-sn-glycero-3-phosphocholine (DEPC), dipalmitoylphosphatidylglycerol or 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG), or combinations thereof.

15. The process of claim 1 , wherein at least one neutral lipid is selected from triglycerides, propylene glycol esters, ethylene glycol esters, squalene, or combinations thereof.

16. The process of claim 1 , wherein at least one neutral lipid is selected from tricaprylin, or triolein or combination of the two.

17. The process of claim 1 , wherein the multivesicular liposomes are characterized by an internal pH of about 8 to about 9.

18. The process of claim 7 , wherein the multivesicular liposomes are characterized by an internal pH of about 8 to about 9.

19. The process of claim 8 , wherein the multivesicular liposomes are characterized by an internal pH of about 8 to about 9.