Polymorphism of phenylbutazone.

The solid-solid transition of phenylbutazone polymorphs by heating was investigated by differential scanning calorimetry (DSC) and X-ray diffractometry, and also the difference in dissolution rate due to the polymorphism was confirmed. There were observed three polymorphs of phenylbutazone. Form I melted at 103°, Form II twice at 93° and at 103°, and Form III at 93°. Furthermore, the mutual transition phenomenon by heating among these three polymorphs was observed by DSC. Analyzing the dissolution curves of Forms I and II obtained by the stationary disk method and poltting the saturated concentration of the respective forms, the transition temperature estimated was 98° and the heat of transition 210 cal/mole. Form III was transformed to Form II through compression above a certain compressional pressure and to the intermediate form of Form II and Form III (designated here as "pseudo-Form III") under the compressional pressure 1 ton/cm2. Therefore, the intrinsic dissolution rate of Form III was not obtained. However, the dissolution rate of "pseudo-Form III" was faster than any of Form I and II. Accordingly, it was suggested that if the transition of Form III could be suppressed, more soluble preparations of phenylbutazone would be available.