NANOPARTICULATE MELOXICAM FORMULATIONS
The present invention is directed to nanoparticulate compositions comprising meloxicam particles having an effective average particle size of less than about 2000 nm.
1 .- 23 . (canceled)
24 . An oral dosage form comprising: (a) particles of meloxicam or a salt thereof having an effective average particle size of less than or about 2000 nm; and (b) at least one surface stabilizer adsorbed on the surface of the particles of meloxicam or a salt thereof.
25 . The oral dosage form of claim 24 , wherein the meloxicam or a salt thereof is selected from the group consisting of a crystalline phase, an amorphous phase, and a semi-crystalline phase.
26 . The oral dosage form of claim 24 , wherein the effective average particle size of the meloxicam particles or a salt thereof is selected from the group consisting of about 1500 nm, less than about 1500 nm, about 1000 nm, less than about 1000 nm, about 900 nm, less than about 900 nm, about 800 nm, less than about 800 nm, about 700 nm, less than about 700 nm, about 600 nm, less than about 600 nm, about 500 nm, less than about 500 nm, about 400 nm, less than about 400 nm, about 300 nm, less than about 300 nm, about 250 nm, less than about 250 nm, about 200 nm, less than about 200 nm, about 150 nm, less than about 150 nm, about 100 nm, less than about 100 nm, about 75 nm, less than about 75 nm, about 50 nm, and less than about 50 nm.
27 . The oral dosage form of claim 24 , wherein the dosage form further comprises one or more pharmaceutically acceptable excipients, one or more pharmaceutically acceptable carriers, or a combination thereof.
28 . The oral dosage form of claim 24 , wherein the meloxicam or a salt thereof is present in an amount of from about 99.5% to about 0.001%, by weight, based on the total combined weight of the meloxicam or a salt thereof and the at least one surface stabilizer.
29 . The oral dosage form of claim 24 , wherein the at least one surface stabilizer is present in an amount of from about 0.01% to about 99.5%, by weight, based on the total combined weight of the meloxicam or a salt thereof and the at least one surface stabilizer.
30 . The oral dosage form of claim 24 , wherein the dosage form further comprises one or more non-nanoparticulate active agents.
31 . The oral dosage form of claim 30 , wherein the non-nanoparticulate active agent is not meloxicam.
32 . The oral dosage form of claim 24 , wherein the dosage form comprises from about 2.5 mg to about 120 mg of meloxicam or a salt thereof.
33 . The oral dosage form of claim 24 , wherein the dosage form comprises about 2.5 mg, about 5 mg, about 7.5 mg, about 15 mg, about 30 mg, about 60 mg, about 75 mg, about 90 mg, about 105 mg, or about 120 mg of meloxicam or a salt thereof.
34 . The oral dosage form of claim 24 , wherein the T max of a 7.5 mg orally administered dose, when assayed in the plasma of a mammalian subject following administration of an initial dose, is less than about 5 hours, less than about 4 hours, less than about 3 hours, less than about 2 hours, less than about 1 hour, less than about 50 minutes, less than about 45 minutes, less than about 40 minutes, less than about 35 minutes, less than about 30 minutes, less than about 20 minutes, less than about 15 minutes, less than about 10 minutes, or less than about 5 minutes.
35 . The oral dosage form of claim 24 , wherein the C max of a 7.5 mg orally administered dose, when assayed in the plasma of a mammalian subject following administration of an initial dose, is greater than about 1 μg/mL, greater than about 3 μg/mL, greater than about 5 μg/mL, greater than about 10 μg/mL, or greater than about 15 μg/mL.
36 . The oral dosage form of claim 24 , wherein the C max , upon administration to a mammalian subject, is greater than about 20%, greater than about 40%, greater than about 60%, greater than about 80%, greater than about 100%, greater than about 140%, greater than about 180%, greater than about 200%, greater than about 240%, greater than about 280%, greater than about 300%, greater than about 340%, greater than about 380%, or greater than about 400% of the C max exhibited by a non-nanoparticulate meloxicam formulation, where meloxicam is present at the same dosage amount.
37 . A method of making an oral dosage form comprising contacting meloxicam or a salt thereof with at least one surface stabilizer for a time and under conditions sufficient to provide an oral dosage form comprising particles of meloxicam or a salt thereof having an effective average particle size of less than or about 2000 nm and at least one surface stabilizer adsorbed on the surface of the particles of meloxicam or a salt thereof.
38 . The method of claim 37 , wherein contacting comprising grinding or homogenizing.
39 . A method for treating a subject in need thereof comprising orally administering to a subject an effective amount of an oral dosage form comprising: (a) particles of meloxicam or a salt thereof having an effective average particle size of less than or about 2000 nm; and (b) at least one surface stabilizer adsorbed on the surface of the particles of meloxicam or a salt thereof.
40 . The method of claim 39 , wherein the subject is a human.
41 . The method of claim 39 , wherein the dosage form comprises from about 2.5 mg to about 120 mg of meloxicam or a salt thereof.
42 . The method of claim 39 , wherein the dosage form comprises about 2.5 mg, about 5 mg, about 7.5 mg, about 15 mg, about 30 mg, about 60 mg, about 75 mg, about 90 mg, about 105 mg, or about 120 mg of meloxicam or a salt thereof.
43 . The method of claim 39 , wherein upon oral administration of a 7.5 mg dose to the subject, the T max , when assayed in the plasma of the subject following administration of an initial dose, is less than about 5 hours, less than about 4 hours, less than about 3 hours, less than about 2 hours, less than about 1 hour, less than less than about 50 minutes, less than about 45 minutes, less than about 40 minutes, less than about 35 minutes, less than about 30 minutes, less than about 20 minutes, less than about 15 minutes, less than about 10 minutes, or less than about 5 minutes.
44 . The method of claim 39 , wherein upon oral administration of a 7.5 mg dose to the subject, the C max , when assayed in the plasma of the subject following administration of an initial dose, is greater than about 1 μg/mL, greater than about 3 μg/mL, greater than about 5 μg/mL, greater than about 10 μg/mL, or greater than about 15 μg/mL.
45 . The method of claim 39 , wherein the C max , upon administration to the subject, is greater than about 20%, greater than about 40%, greater than about 60%, greater than about 80%, greater than about 100%, greater than about 140%, greater than about 180%, greater than about 200%, greater than about 240%, greater than about 280%, greater than about 300%, greater than about 340%, greater than about 380%, or greater than about 400% of the C max exhibited by a non-nanoparticulate meloxicam formulation, where meloxicam is present at the same dosage amount.