Sulfathiazole is a highly polymorphic model system exhibiting at least five polymorphic forms: I, II, III, IV, and V. Polymorph stability is known to be susceptible to solvent environment, and it is established that 1-propanol stabilizes the most metastable form I. This study examines the effect of a range of alcohols on polymorph selection and attempts to elucidate the mechanism. The role of the alcohol functional group in the polymorph selection process is thus investigated and evaluated. Crystals were characterized using optical microscopy, SEM, PXRD, DSC, IR, and single-crystal X-ray diffraction for their polymorphic identity. The role of solvent in the stabilization of polymorphs was investigated by visualizing and calculating energy requirements for the interaction of each solvent molecule with R-and -dimers of sulfathiazole, using Cerius 2 modeling software. This study showed that solvent had a significant impact on polymorph selection. In common with 1-propanol, 1-butanol was found to stabilize form I by inhibiting the formation of the -dimer, which is necessary for nucleation of and transformation to forms II-IV. Shorter chain alcohols and branched chain alcohols such as methanol, 2-propanol, and ethanol did not stabilize form I but stabilized forms II, III, and IV, respectively, showing that it is not only the alcohol functionality but also the steric effects of the alkyl chain that contributed to the effect. Sulfathiazole form I normally has a needlelike morphology. Form I with a modified rodlike morphology was produced by crystallization from 1-propanol with the addition of methanol in low concentration, showing that it is possible to control the morphology and selectively isolate polymorphs.
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