Grinding effect on the thermodynamic and kinetic characterizations of polymorphic transformation of famotidine

Two polymorphs of famotidine, forms A and B, were prepared. The raw material of famotidine used in this study was proved to be a form B. Each famotidine sample ground for different grinding times in a ceramic mortar was determined by differential scanning calorimetry (DSC), Raman and thermal Fourier transform infrared (FT-IR) microspectroscoies, respectively. The effect of grinding process on the polymorphic transformation of famotidine from form B to form A was investigated. The peak intensity of a unique Raman band at 2897 cm^-1 for form B gradually decreased with the grinding time, while the new Raman band at 2920 cm^-1 for form A slowly appeared. The Raman peak intensity ratio of 2897 cm^-1/2920 cm^-1 was linearly decreased with the grinding time (r = 0.99), suggesting that the grinding process could induce the polymorphic transformation of famotidine from form B to form A. The DSC endothermic peaks also confirmed this polymorphic transformation from form B (167degC, DeltaH: 55.68 KJ/mole) to form A (174degC, DeltaH: 49.94 KJ/mole), in which the values of enthalpy were linearly reduced with the increase of grinding time (r = 0.99). The phase transition temperature of the different famotidine ground samples was easily and solely evidenced by using thermal FT-IR microspectroscopy, rather than by DSC analysis. These phase transition temperatures of the form B was maintained to a constant even after 20-30 min grinding. The present study indicates that the grinding process can easily induce the polymorphic transformation of famotidine from form B to form A with a zero-order kinetic.