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Reevaluation of solubility of tolbutamide and polymorphic transformation from Form I to unknown crystal form
Gen Hasegawa1, Takao Komasaka, Rui Bando
1Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
Abstract:
Thermodynamic stability order of tolbutamide between polymorphs was evaluated using calorimetry and spectroscopic analysis. The heat of solution (DeltaH) of Forms I-III measurements were carried out in dimethylsulfoxide between 298.2K and 319.2K. It was found that the DeltaH of Forms II and III was increased nearly parallel with a temperature rise. However, change of the DeltaH of Form I with a temperature rise was not in correspondence with that of other forms. Solubility data confirmed the change in DeltaH of Form I around 308.2K. XRD-DSC measurement of Form I detected a polymorphic transformation (Form I(L)-->unknown form) at 311K. Obtained data suggested that the new crystal form (Form I(H)) would exist above 311K, and the order of thermodynamic stability was "Form III
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