Characterization of polymorphs of tranilast anhydrate and tranilast monohydrate when crystallized by two solvent...

Spherically agglomerated crystals of tranilast (oral antiallergic agent) with improved availability in vitro, as well as improved micromeritic properties such as flowability and packability, were prepared by a novel spherical crystallization technique. The agglomerates of tranilast were found to be composed of new monohydrate I, II, or III, depending on the crystallization solvent and the procedure employed. With dehydration by heating, monohydrate I transformed to the stable alpha form directly. On the other hand, monohydrates II and III converted to the amorphous and beta forms, respectively, followed by further transformation to the alpha form at 110 and 150 degrees C, respectively. The amorphous and beta forms of agglomerates were easily prepared by storing the monohydrates under 0% RH at 30-40 degrees C. Monohydrate II and the amorphous form of the agglomerate with high surface energy could enhance the solubility and the dissolution rate of tranilast. A phase diagram of polymorphs of agglomerated tranilast was constructed to exhibit their interconversions under various humidities and temperatures.