Prolonged release diltazem tablets were prepared using three grades of hydroxypropylmethyl cellulose (HPMC) according to a 3(2) factorial design. The effects of two factors (polymer ratio and polymer type) on drug release t(50%) from hydrophilic matrix tablets were studied at three levels. Tablets were compressed by a flat-faced punch having a diameter of 11 mm using a hydraulic press at 200 kg/cm(2). The in vitro release of diltiazem from tablets was determined according to the USP 23 paddle method in different media (pH 1.2, 4.0, 7.4) at 75 rpm and 37 degrees C. The effect of various excipients (lactose, mannitol and calcium dihydrogen phosphate) on the in vitro release of diltiazem has also been investigated. The releases of diltiazem from tablets which contained lactose and mannitol was greater than from formulations which contained calcium dihydrogen phosphate. Topographic release profiles show that the release of diltiazem decreased as DH increased. The best formulation (F14) contained lactose as a diluent. The F14 formulation showed compared with two commercial products a prolonged release profile whereas the commercial products released 92% and 98%, respectively, during 4 h. All the formulations except F13 which contains mannitol showed Q --> root t kinetics. The most appropriate polymer HPMC K4M with a 1:0.5 ratio has been found by factorial design. The polymer ratio was effective on the release of diltiazem from hydrophilic tablets (p < 0.05).