Dry Grinding of Mefenamic Acid Particles for Enhancement of its Water Dissolution Rate

This paper details an investigation into the enhancement of the water dissolution rate of mefenamic acid (MA) by means of a dry grinding treatment. The physico-chemical properties of the ground MA particles were analyzed by measurements of specific surface area, powder X-ray diffraction patterns, differential scanning calorimetry thermograms and infrared spectra, and the effects of the change in the physico-chemical properties (especially, crystalline structure) on the dissolution rate were studied. The polymorphic transition from Form I (original) to II and the change of the molecular structure of MA did not occur in the grinding treatments. However, the specific surface area of the MA particles increased, and the crystallinity decreased (i.e., the amorphization level increased) as the grinding progressed. Hydrogen bonds formed between the carboxyl groups of the opposed asymmetric MA molecules were broken gradually after the grinding limit was attained in the grinding system, resulting in an effective improvement of the initial dissolution rate.