Infrared studies of the polymorphic states of the fenamates.

Infrared spectroscopy has been used to characterize the polymorphic purity as well as to study the thermal conversion of three of the more common fenamates between their different crystalline forms via measuring changes in the NH stretch region that occur between 3300 and 3350 wavenumbers. Shifts in band frequency for mefenamic acid result from differences in internal hydrogen bonding between the NH group and either the carbonyl or hydroxyl groups of the acid moiety. Due to out-of-plane rotations about the central N-C(ring2) bond additional polymorphic states have been suggested for flufenamic and tolfenamic acids. Rates of conversion are given for flufenamic, mefenamic, and tolfenamic acids at temperatures between 85 and 160 degrees C depending on the polymorphic transition for a particular analyte. Subsequently, these rates are used to calculate the activation energy for the observed polymorphic transition. Values of 71.6, 49.0, and 50.8 kcal/mol are obtained respectively for (1) the polymorph I to II transition of mefenamic acid, (2) the polymorph I to II transition of tolfenamic acid, and (3) the polymorph III to I transition of flufenamic acid.