Effect of enantiotropic uniformity of polymorphic crystals on the chemical stability of suplatast tosilate

摘要

The chemical stability of suplatast tosilate (ST) was evaluated under dry conditions at 60 degrees C, with a focus on the polymorphic forms and crystal uniformity. The intact alpha-form, namely alpha-C type crystals, was crystallized rapidly by adding isopropyl ether into an ethanolic solution of ST. The alpha-C type crystals exhibited low stability at 60 degrees C. In addition to the alpha-C type crystals, two types of alpha-form crystals with different uniformities, namely alpha-A and alpha-B type crystals, were prepared. The alpha-A type crystals were prepared by conversion from the eta-form in aqueous acetone, while the alpha-B type crystals were prepared by recrystallization from 2-propanol at a low supersaturation level. The stability of the alpha-form crystals was as follows: alpha-A > alpha-B > alpha-C. The uniformity of ST crystals was determined according to the newly developed high performance liquid chromatography (HPLC) method. The alpha-C type crystals exhibited inferior chemical stability due to unstable crystalline phases. They showed preferential enrichment and exhibited a unique optical resolution phenomenon. The observed unstable crystalline phases were produced during the crystallization process. alpha-A type crystals, which had high regularity, exhibited excellent stability. Overall, we prepared and evaluated the structures of alpha-form crystals with different uniformities. (C) 2015 Elsevier B.V. All rights reserved.