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This study clearly demonstrates that clathrated water molecules can contribute to both chemical stabilization and destabilization of clathrates. The solid-state stabilities for two isomorphic clathrates of cephalosporin, cefazolin sodium and FK041, were investigated in terms of the effects of water content. The isomorphic ranges of water content were estimated to be 3.5-5 mol/mol for alpha-form cefazolin sodium and 2-4 mol/mol for FK041 hydrate. Upon the isomorphic dehydration, alpha-form cefazolin sodium was destabilized as the water content decreased below 4.25 mol/mol owing to the disruption of hydrogen bonding network in lattice channels. In this case, the hydration of clathrated water up to 4.25 mol/mol contributed to the physical and chemical stability of the crystals. On the contrary, the isomorphic hydration in FK041 hydrate contributed to the chemical destabilization owing to the high water activity. The difference in water activity between alpha-form cefazolin sodium and FK041 hydrate could be attributed to the size of water channels.


Hisashi Mimura, Katsuhiko Gato, Satoshi Kitamura, Teruyuki Kitagawa, Shigetaka Kohda. Effect of water content on the solid-state stability in two isomorphic clathrates of cephalosporin: cefazolin sodium pentahydrate (alpha form) and FK041 hydrate. Chemical & pharmaceutical bulletin. 2002 Jun;50(6):766-70

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PMID: 12045330

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