| 摘要 |
Disclosed is a method for the manufacture of a pharmaceutical tablet that upon ingestion delivers a first drug by immediate release and a second drug by sustained release, defined as a release rate into gastric fluid that is slow enough to leave at least 40% of the second drug unreleased one hour after ingestion, and in which the first drug is at most sparingly soluble in water and the weight ratio of the first drug to the second drug is equal to or less than 0.01:1, the method comprising: (a) dispersing the second drug in a solid matrix to form a unitary core that upon immersion in gastric fluid releases the second drug by sustained release while retaining at least a portion of the mass of the solid matrix as a coherent body until the second drug is fully released, (b) depositing on the second surface of the unitary core an aqueous suspension of particles of the first drug that are equal to or less than 10 microns in diameter, (c) evaporating water from the aqueous suspension thus deposited to leave a solid shell encasing the unitary core and containing the first drug. Or alternatively: (a) combining the second drug with a slid first matrix to form a sustained release layer, the first solid matrix being of a substance that when formed into a coherent body and immersed in gastric fluid releases the second drug by sustained release while retaining at least a portion of the mass of the first solid matrix as a coherent body until the second drug is fully released, and (b) combining particles of the first drug that are equal to or less than about 10 microns in diameter with particles of a second solid matrix to form an immediate release layer adjoined to the sustained-release layer as a layered tablet, the second solid matrix being of a substance that separates into discrete matrix particles immediately upon immersion in gastric fluid.
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