塩酸ベニジピンー水和物のキャラクタライゼーション及びその無水物と一水和物の溶解挙動の比較

抄録

Benidipine hydrochloride, which is one of the 1,4-dihydropyridine-type compounds, is a potent and long-acting calcium antagonist. There is no paper describing the polymorph or hydrate form of benidipine hydrochloride though some 1,4-dihydropyridines have polymorphs or hydrates. We found that the anhydrate form of benidipine hydrochloride changed to the monohydrate form when it was stirred in water. The monohydrate form was suggested to be formed via hydrogen bonding between water molecules and imino groups of dihydropyridine rings, and piperidine NH⁺ groups in the benidipine hydrochloride molecules. We also calculated activation energy by the Ozawa method during the dehydration process from the monohydrate form and obtained 263 kJ/mol. We compared dissolution behaviors in water between the anhydrate form and the monohydrate form. The anhydrate form was strongly suggested to be converted to the monohydrate form after dissolution and its rate of conversion obeyed the first-order rate equation.