Sustained release formulation of a non-steroidal anti-inflammatory drug
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 formulation of multivesicular liposomes for injection, comprising:
meloxicam;
one or more pH modifiers; and
multivesicular liposomes comprising one or more amphipathic lipids and one or more neutral lipids,
wherein meloxicam and at least one pH modifier are encapsulated in a first aqueous phase of the multivesicular liposomes, and
wherein the total potency of the meloxicam in the formulation is at least about 2.2 mg/mL.
2. The formulation of claim 1 , wherein the multivesicular liposomes comprise cholesterol, wherein the one or more amphipathic lipids comprise phosphatidyl choline or salts thereof, phosphatidyl glycerols or salts thereof, or a combination thereof, and wherein the one or more neutral lipids comprise one or more triglycerides.
3. The formulation of claim 2 , wherein the phosphatidyl glycerol is DPPG.
4. The formulation of claim 2 , wherein the phosphatidyl choline is DEPC.
5. The formulation of claim 2 , wherein the triglyceride is selected from triolein, tricaprylin, or a combination of the two.
6. The formulation of claim 1 , wherein the pH modifier comprises lysine or glutamic acid, or a combination thereof.
7. The formulation of claim 1 , wherein the pH modifier comprises an inorganic acid.
8. The formulation of claim 1 , wherein the pH modifier comprises an organic base.
9. The formulation of claim 1 , wherein the pH modifier comprises an inorganic base.
10. The formulation of claim 1 , wherein the pH modifier comprises an organic acid.
11. The formulation of claim 1 , further comprising a pharmaceutically acceptable carrier for subcutaneous, intramuscular, or intraarticular injection, or wound infiltration or instillation.
12. The formulation of claim 1 , wherein the total potency of the meloxicam in the formulation is from about 2.2 mg/mL to about 3.4 mg/mL.
13. The formulation of claim 1 , providing a sustained release of meloxicam for up to 2 weeks.
14. The formulation of claim 1 , wherein the multivesicular liposomes are characterized by an internal pH of about 8 to about 9.