DEVELOPMENT AND EVALUATION OF MODIFIED RELEASE MATRIX TABLETS OF MILNACIPRAN HCL USING MELT GRANULATION TECHNIQUE

摘要

The objective of the present study was to identify critical formulation parameters affecting the drug release from modified release wax matrix tablet of milnacipran hydrochloride employing the concept of design of experiments. The optimized amount of Compritol 888 ATO (intragranular) (X1), lactose (X2) and Compritol 888 ATO (extragranular) (X3) were determined employing simplex lattice design. The tablets were prepared using melt granulation technique. The in vitro drug release study was carried out in an acidic medium (pH 1.2) for 2 h and thereafter the dissolution study was conducted in phosphate buffer (pH 6.8). The selected dependent variables were the cumulative percentage of milnacipran hydrochloride dissolved at 1 (Y1), 8 (Y8), 16 (Y16) and 24 hr (Y24). Mathematical models, correlating the independent variables with dependent variables were evolved. Optimization was performed for the three independent variables using the stated target ranges; Y1<20%; Y8=45±5%; Y16=72±5%; Y24=100%. The optimized amounts of Compritol 888ATO (intragranular) (X^, lactose (X2) and Compritol 888 ATO (extragranular) (X3), were found to be 60, 55 and 30 mg, respectively. The optimized formulation showed a release profile that was close to the predicted values. The drug was released by anomalous diffusion from the optimized formulation. Compritol 888 ATO (intragranular) (X1), lactose (X2) and Compritol 888 ATO (extragranular) (X3) were identified as critical variables.