Phase transition studies of dutasteride crystalline forms

Abstract

Three crystalline forms of dutasteride, known in the literature as forms I, II and III, were studied. It has been proved that only form I is an unsolvated form. Both forms II and III are hydrates (pseudopolymorphs). Phase transition studies performed by thermoanalytical techniques and variable temperature PXRD measurements, in the temperature region from 30 to 180 °C, revealed that dehydration leads to an unstable phase, which finally transforms into form I. Details of the crystal and molecular structure of form I are presented. Dutasteride form I crystallizes in the orthorhombic P2₁2₁2₁ space group with one molecule in the asymmetric part of the unit cell. Dutasteride molecules form a herringbone bond-like pattern with pairs of neighboring ‘heads’ of lactam groups.