Mechanism of the solvent-mediated transformation of taltirelin polymorphs promoted by methanol

✍ Scribed by Shoji Maruyama; Hiroshi Ooshima

• Publisher: Elsevier Science
• Year: 2001
• Tongue: English
• Weight: 201 KB
• Volume: 81
• Category: Article
• ISSN: 1385-8947
• DOI: 10.1016/s1385-8947(00)00193-5

✦ Synopsis

Taltirelin, a central nervous system activating agent, has two crystal forms (␣-and ␤-forms). Previously it has been reported that methanol (MeOH) as a co-solvent promoted the solvent-mediated phase transformation from ␣-form to ␤-form. In the present study, the mechanism of the promotion was investigated. Of the three processes in the solvent-mediated transformation, namely dissolution of the metastable form, nucleation of the stable form, crystal growth of the stable form, MeOH promoted the latter two processes. In particular, the nucleation was strongly promoted. The nOe (nuclear Overhauser effect) data suggested that MeOH promotes the conformational change from the ␣-form to the ␤-form. The solute-MeOH interaction resulted in the formation of pseudo-polymorphs of the ␤-form (2H 2 O•MeOH or H 2 O•2MeOH solvate), although these pseudo-polymorphs were exchangeable to the ␤-form (4H 2 O solvate) under a humid atmosphere.

Based on these findings, a possible mechanism of the transformation of taltirelin polymorphs in the presence of MeOH was discussed.