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  • Title: Physicochemical analyses of phase transition and dehydration processes of a new oral 1beta-methylcarbapenem antibiotic agent, CS-834.
    Author: Kobayashi K, Fukuhara H, Kawamoto I, Hata T, Sekine A, Uekusa H, Ohashi Y.
    Journal: Chem Pharm Bull (Tokyo); 2002 Dec; 50(12):1570-3. PubMed ID: 12499592.
    Abstract:
    The characterizations of the anhydrate (A-form), monohydrate (B1-form), and dihydrate (B2-form) of CS-834 were investigated by powder X-ray diffraction, differential scanning calorimetry (DSC), thermogravimetry-differential thermal analysis (TG-DTA), infrared spectroscopy, and Karl Fischer moisture titration. The typical DSC curve of the B2-form showed five endothermic peaks at 35.0, 46.4, 56.2, 99.2, and 190.4 degrees C and an exothermic peak at 123.4 degrees C. In TG-DTA analysis, the three peaks at 35.0, 46.4, and 56.2 degrees C had a total weight loss of 7.3%, corresponding to the release of two water molecules. From morphological observation under thermomicroscopy, the endothermic peak at 99.2 degrees C was attributed to the melting of the dehydrous crystals (B0-form) and the exothermic peak at 123.4 degrees C to the recrystallization to the A-form crystals. The endothermic peak at 190.4 degrees C was due to the melting of the A-form crystals. After incubation for 6.0 h at 35, 50, 60, and 80 degrees C, the powder X-ray diffraction patterns of the B2-form indicated that it was converted into the A-form via the B1-form and B0-form. Thus CS-834 exists in homologous hydrous crystal forms in multiple-phase transformations with the dehydration of two water molecules.
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