Molecular Behavior of Flufenamic Acid in Physical and Ground Mixtures with Florite

The molecular behavior of flufenamic acid (FFA) was investigated in the physical and ground mixtures with two types of florite, florite R (FR) and florite S (FS). FR is mainly composed of porous calcium silicate while the main component of FS is porous silicon dioxide. The interaction of FFA and nonporous calcium silicate was also studied. Analyses were performed by differential scanning calorimetry, powder X-ray diffraction, and infrared-spectroscopy. Storage and grinding of the mixtures of FFA and FR resulted in the transformation of FFA to the amorphous ionic state, predominantly to calcium salt, and the amorphous state of the drug was found to be more stable in mixtures of higher FR content. In the mixture of FFA and FS, longer storage or grinding was necessary to obtain the amorphous state of FFA, and no change in its chemical state was observed. Differences of the FFA molecular state in the mixtures with FR and FS were attributed to differences of the chemical composition of these additives. Nonporous calcium silicate was found to have limited ability to induce transformation of FFA to the amorphous state as it has small surface area and lacks a porous structure. Stored or ground mixtures of FFA and FR showed marked enhancement in the dissolution behavior of FFA due to the existence of FFA in the amorphous ionic form.