Multiparticulate Modified Release Composition
The invention relates to a multiparticulate modified release composition that, upon administration to a patient, delivers at least one active ingredient in a bimodal or multimodal manner. The multiparticulate modified release composition comprises a first component and at least one subsequent component; the first component comprising a first population of active ingredient containing particles and the at least one subsequent component comprising a second population of active ingredient containing particles wherein the combination of the components exhibit a bimodal or multimodal release profile. The invention also relates to a solid oral dosage form containing such a multiparticulate modified release composition.
1 .- 83 . (canceled)
84 . A multiparticulate modified release solid oral dosage form of hydrocodone or a pharmaceutically acceptable salt thereof comprising:
two populations of hydrocodone containing particles, granules, beads or pellets, said two populations comprising 10 mg, 20 mg, 30 mg, or 40 mg of hydrocodone or a pharmaceutically acceptable salt thereof, said two populations consisting of
a first population of particles, granules, beads or pellets prepared by a method comprising coating sugar spheres of 30/35 mesh as an inert core with a composition comprising about 6.0% (w/w) of hydrocodone or a pharmaceutically acceptable salt thereof, about 1.5% (w/w) of hydroxypropylmethylcellulose, about 2.0% (w/w) of silicon dioxide, and about 90.5% (w/w) of water, and drying the coated sugar spheres, wherein the weight-by-weight percentages, % (w/w), are based on the total of the composition for coating the sugar spheres, wherein the first population of particles, granules, beads or pellets provides an immediate release of hydrocodone, and wherein a size of the first population of particles, granules, beads or pellets is from 0.5 to 0.6 mm; and
a second population of particles, granules, beads or pellets prepared by a method comprising coating the first population of particles, granules, beads or pellets with a composition comprising about 5.5% (w/w) of an ammonio methacrylate copolymer exhibiting pH independent release properties, about 1.0% (w/w) of silicon dioxide, about 1.0% (w/w/) of talc, about 15.0% (w/w/) of acetone, about 72.5% (w/w) of isopropyl alcohol, and about 5.0% (w/w) of water, and drying the coated first population of particles, granules, beads or pellets to remove residual solvents, thereby obtaining the second population of particles, granules, beads or pellets having a moisture content of about 3-6%, wherein the second population of particles, granules, beads or pellets provides a modified release of hydrocodone,
wherein said dosage form providing an in vitro dissolution profile of the hydrocodone such that about 54% by weight of the hydrocodone is released within four hours in vitro measured in a USP Type 1 apparatus at 100 rpm, pH of 2.0 and 37° C.,
wherein said solid oral dosage form comprising 10 mg, 20 mg, 30 mg, or 40 mg of hydrocodone providing a Tmax of hydrocodone of 6.3, 6.0, 6.3, and 6.1 hours respectively, a Cmax of hydrocodone of 8.9, 17.9, 31.7, and 37.5 ng/ml, respectively.
85 . A method of treating pain in a subject, the method comprising administering the multiparticulate modified release solid oral dosage form of claim 84 .