Evaluation of novel starch acetate-diltiazem controlled release tablets in healthy human volunteers

Highly substituted starch acetate can be used to control drug release from directly compressed tablets in vitro. The aim of this study was to evaluate controlled release properties of starch acetate in vivo in humans. Three starch acetate tablet formulations with different in vitro release rates for diltiazem (fast, moderate and slow) were developed. An open, single dose, randomised, four treatment, four period, four sequence cross-over pharmacokinetic study was conducted in eight healthy volunteers. Diltiazem concentrations in plasma were determined by HPLC. Concentration-time profiles of the formulations differed: mean C(max) and AUC(0- infinity ) values of the fast, moderate and slow formulations were 95, 69, 31 ng/ml and 610, 511, 231 ng h/ml, respectively. In vitro-in vivo correlation (IVIVC) was analysed according to the cumulative area under the curves and in vitro release profiles. Acceptable limits of prediction errors were achieved for C(max) and AUC(0-24 h). The moderate formulation and commercial reference tablet showed similar in vitro release profiles and diltiazem concentrations in plasma. In conclusion, direct compression starch acetate formulations control drug release in humans.