Five different polymorphic forms of phenylbutazone were prepared and characterized by differential scanning calorimetry (D.S.C.). Rapid heating rates produced single endothermic peaks due to melting but slower heating rates resulted in interconversion of three of the polymorphs to the more stable form. Interconversion on grinding the polymorphs was also observed. From equilibrium solubility and intrinsic dissolution rates it was concluded that the dissolution process could be described by the Berthoud model. The effect of some tablet excipients on the dissolution process is briefly reported.

The dissolution rate of phenylbutazone from tablets after disintegration has been used to determine whether the drug particles underwent crushing or bonding during compression. Two polymorphic forms of the drug were used and the predominant effect for high drug concentration (60%), during compression was dependent upon the original particle size of the drug and its polymorphic form. With a low drug concentration (10%) in the tablet, the diluent protected the drug particles from bonding together. The particle size change of the drug during compression was affected by the nature of the diluent present. Lactose had an abrasive action on Form A phenylbutazone compared with Avicel but had little effect on the more ductile Form B. When the contact time of compression was decreased from 29 to 0.26 s, the 6 microns particles of drug showed less bonding at the shorter time (faster rate of compression) but the effect observed with the larger particles was independent the compression rate.