| 摘要 |
<p>Disclosed is a solid oral extended release pharmaceutical dosage form comprising a multi-layered extended release matrix formulation with sandwich-type or half sandwich-type structure, the extended release matrix formulation comprising (1) a first composition forming an active agent-containing first layer of the extended release matrix formulation comprising: (a) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1000000; and (b) at least one active agent (preferably selected from the opioid analgesics hydromorphone hydrochloride or hydrocodone bitartrate); and (2) a second composition forming an active agent-free second layer of the extended release matrix formulation comprising at least one polyethylene oxide, and wherein the extended release matrix formulation preferably has a cracking force of at least about 120 N, and/or a“penetration depth to crack”distance of at least about 1.4 mm. Also disclosed is a process of preparing a solid oral extended release pharmaceutical dosage form as defined above, comprising at least the steps of: (a) combining (1) at least one active agent, and (2) at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000, to yield a first composition for an active agent-containing layer first layer; (b) providing a second composition comprising at least one polyethylene oxide having, based on rheological measurements, an approximate molecular weight of at least 1,000,000 or of less than 1,000,000, to yield a second composition for an active agent-free layer second layer, (c) shaping the compositions form (a) and (b) to form at least a bilayer extended release matrix formulation; and (d) curing said extended release matrix formulation comprising at least a curing step at a temperature which is at least the softening temperature of said at least one polyethylene oxide.</p> |
