Infrared studies of the thermal conversion of mefenamic acid between polymorphic states

An infrared method has been developed and used to study the thermal conversion of mefenamic acid from its polymorphic I form to the polymorphic II form. Rates of conversion for the crystal to crystal transition have been measured at temperatures of 150, 155, and 160 °C and subsequently used to calculate the activation energy for the process. The value of 71.6 kcal/mol obtained using the current infrared method is significantly smaller than a previously reported value of 86.4 kcal/mol that was determined by differential scanning calorimetry. In order to explain this difference, additional HPLC experiments were carried out to evaluate the potential loss of analyte due to sublimation when samples of mefenamic acid are maintained at elevated temperatures in the DSC pans prior to measuring the exothermic event indicative of the polymorph I content of a sample. Based on the current study, the rate of anaylte loss due to sublimation is the likely mechanism explaining the larger reported value for the activation energy of the polymorphic conversion of mefenamic acid obtained by DSC.