Application of experimental design in the examination of the dissolution rate of carbamazepine from formulations. Characterization of the optimal formulation by DSC, TGA, FT-IR and PXRD analysis

Abstract

Poor solubility is one of the key reasons for the poor bioavailability of carbamazepine drugs. This study considers formulation of solid surfactant systems with carbamazepine, in order to increase its dissolution rate. Solid-state surfactant systems were formed by application of fractional experimental design. Poloxamer 237 and Poloxamer 338 were used as the surfactants and Brij (R) 35 was used as the co-surfactant. The ratios of the excipients and carbamazepine were varied and their effects on the dissolution rate of carbamazepine were examined. Moreover, the effects of the addition of natural (diatomite) and a synthetic adsorbent carrier (Neusilin (R) UFL2) on the dissolution rate of carbamazepine were also tested. The prepared surfactant systems were characterized and the influences of the excipients on possible changes of the polymorphous form of carbamazepine examined by application of analytical techniques (DSC, TGA, FT-IR and PXRD). It was determined that an appropriate selection of the excipient type and ratio could provide a significant increase in the carbamazepine dissolution rate. By application of analytical techniques, it was found that the employed excipients induce a transition of carbamazepine into the amorphous form and that the selected sample was stable for three months, when kept under ambient conditions.