Sibutramine hydrochloride (SH) is used for the treatment of obesity. The comprehensive physical characterization of drug and drug product is gaining importance due to the potential impacts of phase transitions on the drug productís quality and performance. In this work, the kinetics of dehydration of SH-monohydrate were studied using thermogravimetry-differential thermal analysis (TG-DTA) and the solid-state characterization was done by using differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD) and scanning electron microscopy (SEM). The weight loss data obtained from thermogravimetry (TG) was used for non-isothermal kinetics analysis and the well accepted Coats-Redfern model fitting approach was applied to determine kinetic parameters. Total thirteen solid state reaction models were evaluated, diffusion control (Crank) model found to be the best fit model for this reaction with an excellent correlation 0.9984. The values of Arrhenius parameters, activation energy (Ea) and pre-exponential factor (A) were found to be 34 kcal/mol and 3.23x1016 sec-1 respectively. The dehydration of SH Monohydrate resulted anhydrous SH with a distinct x-ray diffraction profile and crystal morphology.
Dehydration, Sibutramine hydrochloride, Model fitting, Kinetics, PXRD, TG, DSC