Preparation of Amorphous and Polymorph Piretanide and Their Physicochemical Properties and Solubilities

概要

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We prepared piretanide polymorphs by a new recrystallization procedure maximizing the solubility difference based on the pH difference of the solution. A new polymorph, form C, was formed at an acid-base molar ratio of ≧1 : 1,and amorphous form at <0.975 : 1. At the molar ratio of HCl being 0.975-1,a mixture of form C and the amorphous form was generated. By X-ray powder diffractometry, the amorphous form showed no diffraction peak, and form C was significantly different from forms A (bulk material, BM) and B (polymorph). FT-IR spectra of form C and the amorphous form were significantly different from those of forms A and B at around 1700 and 3200-3400 cm^<-1>. The DSC curve of the amorphous form showed exothermic peaks at 136 and 209℃ and endothermic peaks at 207 and 225℃ (corresponding to the melting point of BM), whereas that of form C showed an exothermic peak at 143℃ and endothermic peaks at 132 and 224℃ (corresponding to the melting point of BM). By the dispersed amount method, the solubilities of the amorphous form and form C were almost the same as that of form B and 2.0- and 1.4-fold higher than that of form A (8.3mg/100ml) in JPXII first fluid (pH 1.2) and were about 4.5-fold higher than those of forms A and B (about 200mg/100ml) in JPXII second fluid (pH 6.8) at 37℃.
社団法人日本薬学会の論文
1996-08-15