Physicochemical analyses of phase transition and dehydration processes of a new oral 1beta-methylcarbapenem antibiotic agent, CS-834.

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.

• Authors: Katsuhiro Kobayashi, Hiroshi Fukuhara, Isao Kawamoto, Tadashi Hata, Akiko Sekine, Hidehiro Uekusa, Yuji Ohashi
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 50 Issue 12 Pg. 1570-3 (Dec 2002) ISSN: 0009-2363 [Print] Japan
• PMID: 12499592 (Publication Type: Journal Article)

Chemical References

• Carbapenems
• CS 834

Topics

• Administration, Oral
• Calorimetry, Differential Scanning
• Carbapenems (administration & dosage, chemistry)
• Desiccation
• Drug Design
• Drug Stability
• Spectroscopy, Fourier Transform Infrared
• Titrimetry
• X-Ray Diffraction