Novel Formulation of Meloxicam

Abstract

Unit dosage forms of meloxicam containing either 5 mg or 10 mg of meloxicam that provide effective pain relief and have desirable pharmacokinetic properties are described. The unit dosage forms can provide pain relief when a single unit dose is administered to a patient and useful for treating pain such as osteoarthritis pain at a relatively low systemic exposure to meloxicam.

What is claimed is: 
     
         1 . A unit dosage form of a pharmaceutical composition comprising 5 mg of meloxicam, wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma AUC (0-∞) of 7500-20000 h*ng/ml. 
     
     
         2 . The unit dosage form of  claim 1 , wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma Cmax of 350-950 ng/ml. 
     
     
         3 . The unit dosage form of  claim 1 , wherein the particles of meloxicam have a median particle size, on a volume average basis, between 100 nm and 5000 nm. 
     
     
         4 . The unit dosage form of  claim 1 , wherein the D(0.9) of the particles of meloxicam is less than 3000 nm. 
     
     
         5 . The unit dosage form of  claim 1 , wherein the surface weighted mean diameter (D[3,2]) of the particles of meloxicam is between 100 nm and 800 nm. 
     
     
         6 . The unit dosage form of  claim 1  wherein the volume weighted mean diameter (D[4,3]) of the particles of meloxicam is between 400 nm and 1300 nm. 
     
     
         7 . The unit dosage form of  claim 1  wherein the dissolution rate is such that, when tested using USP Apparatus 1 (baskets) set to rotation speed of 100 RPM in 500 mL of pH 6.1 phosphate buffer with 0.1% sodium lauryl sulfate (SLS) at 37° C.±0.5° C., at least 80% of the meloxicam dissolves in a time period selected from: 30 minutes or less; 20 minutes or less; 10 minutes or less; 8 minutes or less; 7 minutes or less; 6 minutes or less; and 5 minutes or less. 
     
     
         8 . The unit dosage form of  claim 1  wherein the dissolution rate is such that, when tested using USP Apparatus 1 (baskets) set to rotation speed of 100 RPM in 500 mL of pH 6.1 phosphate buffer with 0.1% sodium lauryl sulfate (SLS) at 37° C.±0.5° C., at least 90% of the meloxicam dissolves in a time period selected from: 30 minutes or less; 20 minutes or less; 10 minutes or less; 8 minutes or less; 7 minutes or less; 6 minutes or less; and 5 minutes or less. 
     
     
         9 . The unit dosage form of  claim 1 , wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a median plasma tmax of 1 to 3 hrs. 
     
     
         10 . The unit dosage form of  claim 1 , wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma AUC (0-∞) that is 80% to 125% of 13610 ng-h/ml. 
     
     
         11 . The unit dosage form of  claim 1 , wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma AUC(0-∞) that is 60% to 80% of the AUC(0-∞) of 7.5 mg Mobic tablets. 
     
     
         12 . The unit dosage form of  claim 1 , wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma Cmax that is 80% to 125% of the Cmax of 7.5 mg Mobic tablets. 
     
     
         13 . A unit dosage form comprising 10 mg of meloxicam, wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma AUC (0-∞) of 16000-44000 h*ng/ml. 
     
     
         14 . The unit dosage form of a  claim 13 , wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean blood plasma Cmax of 700-1900 ng/ml. 
     
     
         15 . The unit dosage form of  claim 13 , wherein the particles of meloxicam have a median particle size, on a volume average basis, between 100 nm and 5000 nm. 
     
     
         16 . The unit dosage form of  claim 13 , wherein the D(0.9) of the particles of meloxicam is less than 3000 nm. 
     
     
         17 . The unit dosage form of  claim 13 , wherein the surface weighted mean diameter (D[3,2]) of the particles of meloxicam is between 100 nm and 800 nm. 
     
     
         18 . The unit dosage form of  claim 13  wherein the volume weighted mean diameter (D[4,3]) of the particles of meloxicam is between 400 nm and 1300 nm. 
     
     
         19 . The unit dosage form of  claim 13  wherein the dissolution rate is such that, when tested using USP Apparatus 1 (baskets) set to rotation speed of 100 RPM in 1000 mL of pH 6.1 phosphate buffer with 0.1% sodium lauryl sulfate (SLS) at 37° C.±0.5° C., at least 80% of the meloxicam dissolves in a time period selected from: 30 minutes or less; 20 minutes or less; 15 minutes or less; 14 minutes or less; 13 minutes or less; 12 minutes or less; 11 minutes or less; 10 minutes or less; and 5 minutes or less. 
     
     
         20 . The unit dosage form of  claim 13  wherein the dissolution rate is such that, when tested using USP Apparatus 1 (baskets) set to rotation speed of 100 RPM in 1000 mL of pH 6.1 phosphate buffer with 0.1% sodium lauryl sulfate (SLS) at 37° C.±0.5° C., at least 90% of the meloxicam dissolves in a time period selected from: 30 minutes or less; 20 minutes or less; 15 minutes or less; 14 minutes or less; 13 minutes or less; 12 minutes or less; 11 minutes or less; 10 minutes or less; and 5 minutes or less. 
     
     
         21 . The unit dosage form of  claim 13 , wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a median plasma tmax of 1 to 3 hrs. 
     
     
         22 . The unit dosage form of  claim 13 , wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma AUC (0-∞) that is 80% to 125% of 29,173 ng-h/ml. 
     
     
         23 . The unit dosage form of  claim 13 , wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma Cmax that is 80% to 125% of 1253 ng/ml. 
     
     
         24 . The unit dosage form of  claim 13 , wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma AUC(0-∞) that is 60%-80% of the mean plasma AUC(0-∞) of 15 mg Mobic tablets. 
     
     
         25 . The unit dosage form of  claim 13 , wherein a single dose, upon oral administration to a population of healthy adults in the fasted state, provides a mean plasma Cmax that is 80%-125% of the mean plasma Cmax of 15 mg Mobic tablets. 
     
     
         26 . A unit dosage form of a pharmaceutical composition comprising 10 mg of meloxicam, wherein a single dose, upon oral administration to a population of healthy adults in the fed state, provides a mean plasma Cmax of 525-1500 ng/ml. 
     
     
         27 . The unit dosage form of  claim 26 , wherein a single dose, upon oral administration to a population of healthy adults in the fed state, provides a median plasma Tmax of 3 to 7 hrs. 
     
     
         28 . The unit dosage form of  claim 26 , wherein a single dose, upon oral administration to a population healthy adults in the fed state, provides a mean plasma AUC (0-∞) of 15000-42000 h*ng/ml. 
     
     
         29 . The unit oral dosage form of  claim 26 , wherein a single dose, upon oral administration to a population of healthy adults in the fed state, provides a mean plasma Cmax that is 80% to 125% of 974 ng/ml. 
     
     
         30 . The unit oral dosage form of  claim 26 , wherein a single dose, upon oral administration to a population of healthy adults in the fed state, provides a mean plasma AUC(0-∞) that is 80% to 125% of 27,146 ng/ml.