Effect of temperature and kneading solution on polymorphic transformation of mefenamic acid during granulation

Form II, mefenamic acid (MA) transformed into form I in various solvents at 25, 33 or 37 °C during kneading, and the transformation rate was dependent on the experimental conditions. The transformation rate of form II measured by X-ray diffraction method increased with increase of temperature and content of ethanol. The kinetic process of form II followed three-dimensional growth of nuclei equation, and the transformation rate constant, k, and induction period, IP, were estimated based on the equation. The k of form II decreased with decrease of temperature, but the IP increased. The transformation rate of form II in ethanol was the fastest, and that in distilled water was the lowest, it was dependent on the solubility of MA in the solution. On the other hand, the k of phase transformation added 1% form I crystals as seeds was much larger than that without seeds, but the IP significantly decreased by seed addition. The result suggested that IP was a nucleus formation process, but the seed addition did not affect the crystal growth process.