Design and Evaluation of pH Sensitive Multi- Particulate Systems for Chronotherapeutic Delivery of Diltiazem Hydrochloride

A pH sensitive multi-particulate system intended to approximate the chronobiology of angina pectoris is proposed for colonic targeting. The system comprising of Eudragit S-100 coated pellets was designed for chronotherapeutic delivery of diltiazem hydrochloride. The drug loaded core pellets were produced by aqueous extrusion spheronization technique using microcrystalline cellulose as a spheronizing aid and PVP K 30 as a binder. Different coat weights of Eudragit S-100 were applied to the drug loaded pellets in an automatic coating machine to produce the pH sensitive coated pellets. Scanning electron microscopy revealed that the core pellets were discrete, spherical, or oval with a slightly rough surface whereas the coated pellets were covered with a uniform and continuous acrylic film. Optical microscopic image analysis portrayed that the values of aspect ratio and pellet circularity were close to 1.0, indicating the core pellets were almost spherical in shape. The friability with glass spheres was below 1.0%, signifying the core pellets produced were sufficiently hard. In vitro dissolution studies of the coated pellets performed following pH progression method showed that the drug release from the coated pellets depended on the coat weights applied and pH of the dissolution media. Since, diltiazem hydrochloride is a drug, which exhibits a high solubility, it would be possible to minimize drug release from the coated pellets below pH 7.0, and effectively release the drug at colonic pH only with higher coat loads (15-20% weight gain).