Composition for pulsatile delivery of diltiazem and process of manufacture

Abstract

A once-a-day controlled release drug delivery system of diltiazem hydrochloride is provided, which is bioequivalent in plasma profile of Cardizem CD. The fast, medium, and slow release fractions are prepared using various compositions and weight gains. The individual fill weights are computed and then are filled into the same capsule using specialized encapsulation equipment using a triple-filling process. A preferred membrane dispersion that is used for preparing the fast release fraction contains 0.2% of sodium lauryl sulfate along with 20% of water soluble plasticizer (triethyl citrate), and 2% silicone dioxide, based on quaternary polymethacrylate on the weight basis. This combination provides an initial pulsatile burst after a lag time of 2 hours, leading to in-vivo bioequivalence. The preferred membrane dispersion that is used for preparing the medium release and the slow release fractions contain 16% of water soluble plasticizer along with 5% silicone dioxide, based on quaternary polymethacrylate. This combination provides an optimal glass transition temperature that allows for the preparation of exceptionally increased weight gains. Additionally, it provides targeted input of drug release for achieving bioequivalence. Regardless of significant in-vitro inequivalence to the release rate profile of the innovator product, the in vivo-equivalence data comply with required regulatory guidelines.

Dependencies are inferred from the claim text.