| 主权项 |
1. A process of preparing a solid oral extended release pharmaceutical dosage form, comprising at least the steps of:
(a) combining at least (1) at least one polyethylene oxide and (2) at least one active agent comprising oxycodone hydrochloride, to form a composition; (b) shaping the composition to form an extended release matrix formulation; and (c) curing said extended release matrix formulation comprising at least a curing step of subjecting the extended release matrix formulation to a temperature which is at least the softening temperature of said polyethylene oxide for a time period of at least about 1 minute, wherein the at least one polyethylene oxide, based on rheological measurements, has a molecular weight of approximately 4,000,000 and is at least 79% by weight of the composition; and wherein (i) wherein the cured shaped extended release formulation is flattened without breaking to no more that about 60% of its thickness before flattening, said flattened cured shaped extended release formulation has an in-vitro dissolution, when measured in a USP Apparatus 1 (basket) at 100 rpm and at 37° C. in 900 ml of simulated gastric fluid having no enzymes and having 40% ethanol, wherein the percent amount of oxycodone hydrochloride release at 0.5 hours of dissolution deviates no more than about 20% points from the corresponding in-vitro dissolution of said formulation when measured in a USP Apparatus 1 (basket) at 100 rpm and at 37° C., in 900 ml of simulated gastric fluid having no enzymes and having no ethanol; (ii) between 5 and 40% (by weight based upon total weight of oxycodone hydrochloride in said cured shaped extended release matrix formulation) of oxycodone hydrocodone in said cured shaped extended release matrix formulation is released after 0.5 hours, when measured in a USP Apparatus 1 (basket) at 100 rpm and at 37° C. in 900 ml of simulated gastric fluid having no enzymes and having 40% or 0% ethanol; or
(iii) a combination of (i) and (ii). |
