Pharmaceutical compositions for intraarticular delivery
The present invention provides methods of treating arthritis. A sustained release composition comprising liposomes and one or more therapeutic agent or a pharmaceutically acceptable salt thereof is administered to a subject in need thereof. The liposomes may be in an aqueous suspension. The sustained release composition can be administered intraarticularly.
1. An intraarticular injection, which is prepared by a process comprising:
providing a lyophilized lipid cake comprising a mixture of a first phospholipid and a second phospholipid, the first phospholipid being phosphatidylcholine (PC), and the second phospholipid being phosphatidylglycerol (PG); and
reconstituting the lyophilized lipid cake with an aqueous solution comprising one or more therapeutic agents to form the intraarticular injection.
2. The intraarticular injection of claim 1 , wherein the first phospholipid is 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC), soy phosphatidylcholine (SPC), or egg phosphatidylcholine (EPC) and the second phospholipid is dipalmitoylphosphatidylglycerol (DOPG).
3. The intraarticular injection of claim 1 , wherein said lyophilized lipid cake comprises cholesterol at a mole percent ratio about 10 to about 33 based on the total amount of the first phospholipid, the second phospholipid and cholesterol.
4. The intraarticular injection of claim 2 , wherein the first phospholipid is DOPC and the second phospholipid is DOPG.
5. The intraarticular injection of claim 1 , wherein the mixture of the first phospholipid and the second phospholipid are preformed into liposomes with a cryoprotectant before processing into a lipid cake.
6. The intraarticular injection of claim 5 , wherein the cryoprotectant is mannitol.
7. The intraarticular injection of claim 1 , wherein the therapeutic agent comprises a water-soluble steroid or a pharmaceutically acceptable salt thereof.
8. The intraarticular injection of claim 7 , wherein the water-soluble steroid is dexamethasone sodium phosphate (DSP).
9. The intraarticular injection of claim 7 , wherein the water soluble steroid has a potency equivalent from about a 2 mg dose to about 8 mg dose of dexamethasone.
10. The intraarticular injection of claim 1 , wherein the therapeutic agent comprises a nonsteroidal anti-inflammatory drug or a pharmaceutically acceptable salt thereof.
11. The intraarticular injection of claim 10 , wherein the nonsteroidal anti-inflammatory drug or the pharmaceutically acceptable salt thereof is indomethacin or indomethacin sodium.
12. The intraarticular injection of claim 10 , wherein the concentration of the nonsteroidal anti-inflammatory drug or the pharmaceutically acceptable salt thereof is about 4.65 to about 5 mg/ml.
13. The intraarticular injection of claim 1 , wherein the therapeutic agent comprises a disease modifying anti-rheumatic drug (DMARD).
14. The intraarticular injection of claim 13 , wherein the DMARD comprises a TNF-a antagonist.
15. The intraarticular injection of claim 14 , wherein the TNF-a antagonist is etanercept.
16. The intraarticular injection of claim 15 , wherein the concentration of etanercept in the composition is about 42.8 mg/ml to about 50 mg/ml.
17. The intraarticular injection of claim 14 , wherein the TNF-a antagonist is adalimumab.
18. The intraarticular injection of claim 13 , wherein the DMARD comprises methotrexate or a pharmaceutically acceptable salt thereof.
19. The intraarticular injection of claim 18 , wherein the pharmaceutically acceptable salt is methotrexate sodium.
20. The intraarticular injection of claim 18 , wherein the concentration of methotrexate or the pharmaceutically acceptable salt thereof is about 2.3 to about 2.5 mg/ml.
21. The intraarticular injection of claim 1 , wherein the therapeutic agent is encapsulated in an aqueous medium of liposomes.
22. An intraarticular injection, which is prepared by a process comprising:
providing a lyophilized combination of one or more therapeutic agents and a lipid cake comprising a mixture of a first phospholipid and a second phospholipid, the first phospholipid being phosphatidylcholine (PC), and the second phospholipid being phosphatidylglycerol (PG); and
reconstituting the lyophilized combination of the one or more therapeutic agents and the lipid cake with an aqueous solution to form the intraarticular injection.