Physicochemical analyses of phase transition and dehydration processes of a new oral 1beta-methylcarbapenem antibiotic agent, CS-834.
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.
Kobayashi
Katsuhiro
K
Process Development Laboratories, Sankyo Co Ltd, Kanagawa, Japan.
Fukuhara
Hiroshi
H
Kawamoto
Isao
I
Hata
Tadashi
T
Sekine
Akiko
A
Uekusa
Hidehiro
H
Ohashi
Yuji
Y
D000284:Administration, Oral; D002152:Calorimetry, Differential Scanning; D015780:Carbapenems / Q000008:administration & dosage / Q000737:chemistry*; D003890:Desiccation; D015195:Drug Design; D004355:Drug Stability; D017550:Spectroscopy, Fourier Transform Infrared; D017186:Titrimetry; D014961:X-Ray Diffraction
D015780:Carbapenems; C107030:CS 834