Disappearing polymorphs and the role of reaction by-products: the case of sulphathiazole

A combined modelling and experimental strategy has been applied to the problem of reaction by-product influence on the appearance of sulphathaizole polymorphs from aqueous solution. From pure aqueous solution after 24 h the most stable phase, form IV was isolated. This work shows for the first time that a reaction by-product, ethamidosulphathiazole, from the final hydrolysis stage at concentrations as low as 1 mol.% stabilises the metastable modification, form I. In the presence of 1.0-0.5 mol.% forms II and III are stabilised. Only at concentration below 0.5 mol.% does the transformation proceed to form IV as in the pure solution. The role of the impurity was accounted for from an analysis of the respective hydrogen bond networks and crystal morphologies of each phase. (C) 1998 Elsevier Science B.V. All rights reserved.