Compatibility studies of promethazine hydrochloride with tablet excipients by means of thermal and non-thermal methods.

The compatibility of promethazine hydrochloride (PMZ) with various tableting excipients has been investigated by isothermal stress testing (IST) and differential scanning calorimetry (DSC). DSC thermograms of PMZ and each of the excipients investigated were compared with their corresponding physical mixtures (1:1) for evaluation. Furthermore, Fourier transform infrared spectroscopy (FTIR) data was used to corroborate the results of DSC and IST. A preliminary sustained release tablet formulation of the drug, prepared using compatible excipients, was stored under accelerated storage conditions (40 degrees C/75% RH) and analyzed for stability, drug release and bioadhesion characteristics for up to 3 months. Based on DSC results alone, drug-excipient interactions were observed with Pearlitol SD200, lactose monohydrate and zinc stearate. Chromatographic analysis of the stressed binary mixture (stored at 55 degrees C for 3 weeks) containing PMZ-lactose monohydrate showed brown discoloration indicating potential interaction. However, stressed physical mixtures of PMZ-Pearlitol SD200 and PMZ-zinc stearate indicated compatibility as opposed to the thermal analysis. The tablet formulation was found to be very stable after 3 months of storage at accelerated stability conditions. Also, the release profiles and bioadhesive properties were found to be unaltered. Thus, both thermal and non-thermal methods were utilized to successfully evaluate the compatibility of excipients with PMZ and the tablet formulation was found to be stable.