product consisting of diltiazem in retardformen.

摘要

A sustained release diltiazem formulation for oral administration comprising a pellet having a central sugar sphere a plurality of alternating first and second layers surrounding the sphere to form a core, the first layer comprising a water soluble pharmaceutically acceptable polymeric material and the second layer comprising diltiazem or a pharmaceutically acceptable salt thereof and an outer membrane surrounding the plurality of layers. The outer membrane comprises first inner membrane layers of ethylcellulose. The outer membrane also comprises an outer membrane coating of a water insoluble pharmaceutically acceptable polymeric material, a plasticizer and a lubricant, in from one to five or more layers. The number of layers and the coating of the two outer membrane layers are effective to permit the release of the diltiazem from the pellet at a rate allowing controlled absorption thereof over a twelve or twenty four hour period following oral administration, the rate being measured in vitro as a dissolution rate of the pellet, which when measured in an aqueous solution in a paddle apparatus according to U.S. Pharmacopeia XXII, substantially corresponds to the following dissolution pattern: from 15 to 40% of the total diltiazem is released after 4 hours of measurement; from 40 to 70% of the total diltiazem is released after 8 hours of measurement; from 50 to 85% of the total diltiazem is released after 12 hours of measurement; and from 70 to 100% of the total diltiazem is released after 24 hours of measurement.