Development and in vitro evaluation of multiparticulate sustained release carbamazepine formulation.

The objective of the present study was the development and the in vitro evaluation of extended release multiparticulate dosage forms with carbamazepine, starting from drug crystals of established granulometry as cores and using Eudragit NE aqueous dispersions as coating film polymer in a bottom spray fluid bed coating system. The chosen independent variables, i.e., the quantity of film coating (Eudragit NE) and the % of hydrophilic polymer in film coating that act as pores generating (hydroxypropyl methylcellulose ratio) were optimized with a two-factor, three-level central composite experimental design. The chosen dependent variables were cumulative percentage values of carbamazepine released after 1, 2, 4, 6, 8 and 12 h and Peppas kinetic release equation parameters (k and n). Based on the experimental design, different carbamazepine formulations were proposed and their release profiles were determined. The second-order polynomial model coefficients and response surface plots were used to analyze the relation between the dependent and the independent variables. The optimized formulation prepared according to computer-determined levels provided a release profile which was close to the predicted values. The dissolution profile of carbamazepine from the coated crystals and tablets prepared with them were similar, and were unchanged after storage for 3 months under controlled conditions.