Abstract
Polymorphs is getting to be increasingly important problems in pharmaceutical industries, because the bioavailability and some other properties depend on each polymorph. Therefore, the control of the crystallization including polymorphs is very important. As a crystallization method anti-solvents are frequently used in pharmaceutical industries. In this crystallization the solvent compositions change with time. At the same time the various operational factors also influence on the polymorphic crystallization behavior including transformation. However, the quantitative details of crystallization behavior and the mechanism of the anti-solvent crystallization has not been known. In this study the thermodynamic stability,the transformation and the crystallization behavior of the polymorphs of the thiazole-derivative (BPT), which is one of the pharmaceuticals, were investigated in methanol-water mixture solvents at 323K. BPT has three polymorphs (A, B and C) and two solvated crystals (BH and D). The thermodynamic stability of crystals and the transformation behaviors are complicated. Such behaviors were related with the temperature and the solvent compositions.
The crystallization was also carried out by adding water which is an anti-solvent for BPT to the solutions. It cleared that at 323 K only the meta-stable form crystallizes and the crystallization behavior depends on the initial concentration of the solute and the addition rate of water. At low initial concentrations, BH crystallized independently of the addition rate of water. However, at higher initial concentrations, the D form crystallized in addition to the BH form, especially at low water-addition rates. It was also found that the crystallized form transform to several different forms, and the transformation characteristics are dependant upon the initial concentration of BPT.
