New approach for preparation of metastable phenylbutazone polymorphs

Abstract

Polymorphism of phenylbutazone is one of the most studied but also most elusive problems being complicated by the easy oxidation of this drug in solutions and melt resulting in variable thermal behavior of crystal forms prepared. Reproducible methods excluding the oxidation process are elaborated in the present work for preparation of metastable phenylbutazone polymorphs, which perform solid-state transitions to the stable form instead of the melting–crystallization transformation observed for partially oxidized forms. These methods use solid-state repulsion of the guest included in the phenylbutazone solvate by the vapor of another guest and desolvation of a very unstable solvate. Polymorphs and solvates prepared were characterized by a simultaneous method of thermogravimetry and differential scanning calorimetry and by powder X-ray diffractometry. The type of phase transition induced by heating in the guest-free crystal forms was confirmed using thermomicroscopy. The main product of phenylbutazone oxidation, 4-hydroxyphenylbutazone, and a new 1 : 1 solvate of phenylbutazone with acetonitrile were prepared and characterized by single crystal X-ray diffraction.