Three anhydrous forms and a dihydrate form of quifenadine hydrochloride: a structural study of the thermodynamic stability and dehydration mechanism

Abstract

Crystal structures of dihydrate (DH) and three anhydrous forms (A, B and C) of quifenadine (1-azabicyclo[2.2.2]oct-8-yl-diphenyl-methanol) hydrochloride are presented, and crystal structure information is used to explain and rationalize the relative stability of polymorphs and observed phase transformations. The dehydration mechanism of the hydrate is provided by interpreting the results obtained in studies of crystal structures, dehydration kinetics and thermal analysis. Structural analysis is used to explain the observed relative stability of the anhydrous phases and the hydrate. The crystal structures have been determined either from single crystal (form DH) or from powder diffraction data (forms A, B and C). All three polymorphs consist of similar hydrogen bonded tetramers, and the structural differences arise due to differences in conformation or/and molecular packing.