Pharmaceutical compositions of meloxicam
The present invention relates to storage stable emulsion formulations of meloxicam or its pharmaceutically acceptable salts, solvates and hydrates thereof suitable for parenteral administration.
1. A method of treating osteoarthritis, rheumatoid arthritis, and acute pain comprising parenterally administering to a human patient, a pharmaceutical formulation comprising a stable emulsion of meloxicam, wherein said emulsion comprises:
meloxicam or a pharmaceutically acceptable salt thereof;
a first emulsifier;
an oil which is soybean oil;
a second emulsifier which is ethanol;
a pH modifier;
an osmotic agent
and water;
wherein the meloxicam is dissolved in the ethanol and the soybean oil to form an oil phase;
wherein the pH of the emulsion ranges from about 7.0 to 10;
wherein said emulsion has an intensity-weighted mean droplet diameter less than about 300 nm.
2. The method of claim 1 , wherein the emulsion comprises 5 wt/wt % to 25 wt/wt % of the first emulsifier.
3. The method of claim 1 , wherein the first emulsifier is a phospholipid.
4. The method of claim 1 , wherein the first emulsifier is egg lecithin.
5. The method of claim 1 , wherein the emulsion comprises 5 wt/wt % to 15 wt/wt % of soybean oil.
6. The method of claim 1 , wherein the pH modifier is sodium oleate.
7. The method of claim 1 , wherein the emulsion comprises less than 10 wt/wt % of ethanol.
8. The method of claim 1 , wherein the osmotic agent is sodium chloride or sucrose.
9. A method of treating osteoarthritis, rheumatoid arthritis, and acute pain comprising parenterally administering to a human patient, a pharmaceutical formulation comprising a stable emulsion of meloxicam,
wherein said method comprises preparing the emulsion of meloxicam comprising the steps:
(i) combining meloxicam, a first emulsifier, and a second emulsifier which is ethanol, with an oil which is soybean oil to generate an oil phase in which the meloxicam is dissolved;
(ii) combining water, an osmotic agent and a pH modifier to generate an aqueous phase;
(iii) homogenizing the oil phase with the aqueous phase to generate a coarse emulsion premix;
(iv) homogenizing the coarse emulsion premix at a pressure between 10,000 and 30,000 psi using a microfluidizer to generate the pharmaceutical emulsion; and
(v) sterilizing the pharmaceutical emulsion
wherein said emulsion has an intensity-weighted mean droplet diameter less than about 300 nm.
10. The method according to claim 9 , wherein said step of homogenizing the coarse emulsion premix comprises 4 to 15 passes through the microfluidizer.
11. The method according to claim 9 , wherein said step of sterilizing comprises passing the pharmaceutical emulsion through a filter having a pore size of about 0.2 micrometre.
12. A method of treating osteoarthritis, rheumatoid arthritis, and acute pain comprising parenterally administering to a human patient, a pharmaceutical formulation comprising a stable emulsion of meloxicam, wherein the emulsion comprises: meloxicam or a pharmaceutically acceptable salt thereof;
a first emulsifier;
an oil which is soybean oil;
a second emulsifier which is ethanol;
a pH modifier;
an osmotic agent and water; wherein the meloxicam is dissolved in the ethanol and the soybean oil to form an oil phase;
wherein the pH of the emulsion ranges from about 7.0 to 10,
wherein said first emulsifier is phospholipid, egg lecithin or a mixture thereof, and said ethanol is present in the amount of 10% by weight;
wherein said emulsion has an intensity-weighted mean droplet diameter less than about 300 nm.