Manufacture of oral dosage forms delivering both immediate-release and sustained-release drugs

A method for the manufacture of a pharmaceutical tablet which upon oral ingestion delivers a first drug by substantially 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 about 40% of said second drug unreleased one hour after ingestion, and in which said first drug is at most sparingly soluble in water and the weight ratio of said first drug to said second drug is equal to or less than about 0.01:1, said method comprising:

• combining said second drug with a first solid matrix to form a sustained-release layer, said first solid matrix being of a substance which when formed into a coherent body and immersed in gastric fluid releases said second drug by sustained release while retaining at least a portion of the mass of said first solid matrix as a coherent body until said second drug is fully released therefrom;
• and
• combining particles of said 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 said sustained-release layer as a layered tablet, said second solid matrix being of a substance that separates into discrete matrix particles immediately upon immersion in gastric fluid, using amounts of said first and second drugs selected to achieve said weight ratio.