Structural characterization of polymorphs and molecular complexes of finasteride

The molecular structure of finasteride, 17 beta-(N-tert-butylcarbamoyl)-3-a za-5 alpha-androst-1-en-3-one, and structures of three related crystalline forms have been determined by X-ray analysis. The rigid steroid skeleton of the molecule adopts a half-chair/chair/chair/half-chair conformation. Two peptide groups, one cyclic (lactam) in the ring A and a second being a part of the substituent at C17, an the main factors influencing intermolecular contacts. Different hydrogen-bond interactions of these hydrophilic groups are observed in the crystal structures. An infinite ribbon of finasteride m olecules is formed between lactam groups in the orthorhombic homomolecular crystal (1) obtained from an ethanol solution. The linear molecular complex finasteride-acetic acid (1a) is connected by hydrogen bonds between the la ctam of finasteride and the carboxyl group of acetic acid. The crystallizat ion from an ethyl acetate solution gives a complex structure of bis-finaste ride monohydrate ethyl acetate clathrate (1b) with guest molecule disordere d in channels. Crystals of a second (monoclinic) finasteride polymorph (2) were obtained during thermal decomposition of 1a, and sublimation of 1, 1a and 1b. Two polymorphic forms show different IR spectra. (C) 1998 Elsevier Science B.V. All rights reserved.