NOVEL FORMULATION OF METAXALONE
The present invention relates to methods for producing particles of metaxalone using dry milling processes as well as compositions comprising metaxalone, medicaments produced using metaxalone in particulate form and/or compositions, and to methods of treatment of an animal, including man, using a therapeutically effective amount of metaxalone administered by way of said medicaments.
1 - 41 . (canceled)
42 . A pharmaceutical composition comprising metaxalone, wherein the median particle size of the metaxalone on a particle volume basis is less than 500 nm.
43 . The pharmaceutical composition of claim 42 wherein the median particle size on a particle volume basis is less than 400 nm.
44 . The pharmaceutical composition of claim 42 wherein the median particle size on a particle volume basis is less than 300 nm.
45 . The pharmaceutical composition of claim 42 wherein 90% of the metaxalone, on a particle volume basis, has a particle size that is less than 2000 nm.
46 . The pharmaceutical composition of claim 45 wherein 90% of the metaxalone, on a particle volume basis, has a particle size that is less than 1700 nm.
47 . The pharmaceutical composition of claim 42 further comprising sodium lauryl sulfate
48 . The pharmaceutical composition of claim 42 further comprising lactose monohydrate.
49 . The pharmaceutical composition of claim 42 wherein the T max of the metaxalone when administered to a human subject is less than the T max of a conventional, non-nanoparticulate form of metaxalone administered to a human subject when the composition is administered at the same dosage as the conventional, non-nanoparticulate form.
50 . The pharmaceutical composition of claim 49 wherein the T max of the metaxalone when administered to a human subject is less than the T max of a conventional, non-nanoparticulate form of metaxalone administered to a human subject when the nanoparticulate composition is administered at a 20% lower dosage than the conventional, non-nanoparticulate form.
51 . The pharmaceutical composition of claim 49 wherein the T max is less than about 90% of the T max of a conventional, non-nanoparticulate form of metaxalone administered to a human subject when the composition is administered at the same dosage as the conventional, non-nanoparticulate form.
52 . The pharmaceutical composition of claim 42 wherein the T max of the metaxalone when administered to a human subject in the fasted state is less than the T max of a conventional, non-nanoparticulate form of metaxalone administered to a human subject in the fasted state when the composition is administered at the same dosage as the conventional, non-nanoparticulate form.
53 . The pharmaceutical composition of claim 52 wherein the T max of the metaxalone when administered to a human subject in the fasted state is less than the T max of a conventional, non-nanoparticulate form of metaxalone administered to a human subject in the fasted state when the composition is administered at a 20% lower dosage than the conventional, non-nanoparticulate form.
54 . The pharmaceutical composition of claim 42 wherein the C max of the metaxalone when administered to a human subject is greater than the C max of a conventional, non-nanoparticulate form of metaxalone administered to a human subject when the composition is administered at a 20% lower dosage than the conventional, non-nanoparticulate form.
55 . The pharmaceutical composition of claim 42 wherein the C max of the metaxalone is at least 10% greater.
56 . The pharmaceutical composition of claim 42 when tested in vitro by USP Apparatus II (Basket) method of U.S. Pharmacopoeia at 100 rpm at 37° C. in 1000 ml of 0.01M HCl pH 2 provides a dissolution rate of metaxalone such that greater than 75% (by weight) is released at 1 hour.
57 . The pharmaceutical composition of claim 42 wherein the T max of the metaxalone when administered to a human subject is less than 1 hour.
58 . The pharmaceutical composition of claim 42 wherein the T max of the metaxalone when administered to a human subject is less than 40 minutes.
59 . The pharmaceutical composition of claim 58 wherein the T max of the metaxalone when administered to a human subject is less than 1 hour when dosed in the fed or fasted state at 18 mg or 35 mg.
60 . A method for producing a metaxalone-containing composition, comprising:
dry milling a composition comprising metaxalone and a millable grinding matrix in a mill containing a plurality of milling bodies for a time period sufficient to produce a metaxalone-containing composition comprising particles of metaxalone having a median particle size on a particle volume basis of less than 500 nm dispersed in an at least partially milled grinding matrix.
61 . The method of claim 60 wherein the composition further comprises a surfactant.
62 . The method of claim 60 further comprising combining the metaxalone-containing composition with a facilitating agent.
63 . The method of claim 62 wherein the facilitating agent is selected from a surfactant, polymer, a binding agent, a filling agent, a lubricating agent, a sweetener, a flavoring agent, a preservative, a buffer, a wetting agent, a disintegrant, and an effervescent agent.
64 . The method of claim 60 further comprising processing the metaxalone-containing composition into a unit dosage pharmaceutical composition.
65 . The method of claim 64 wherein the unit dosage composition contains 100 mg of metaxalone.
66 . A unit dosage composition of metaxalone comprising the pharmaceutical composition of claim 42 wherein the unit dosage composition contains 100 mg of metaxalone.
67 . The pharmaceutical composition of claim 42 , wherein administration of the composition to a patient having undergone a surgical dental extraction procedure results in a median time to onset of analgesia of less than 1 hour.
68 . The pharmaceutical composition of claim 42 , wherein administration of the composition to a patient having undergone a surgical dental extraction procedure results in a median time to peak pain relief of less than 4 hours.
69 . The pharmaceutical composition of claim 42 , wherein administration of the composition to a patient having undergone a surgical dental extraction procedure results in a median time to meaningful pain relief of less than 2 hours.