Effect of salt type on hygroscopicity of a new cephalosporin S-3578.
OBJECTIVE
Effect of salt type on hygroscopicity was evaluated using S-3578 salts.


METHODS
The hydration behavior of a sulfate and a nitrate salt of S-3578 were evaluated by powder X-ray diffraction (PXRD), simultaneous measurement of PXRD-differential scanning calorimetry (DSC), moisture sorption analysis, simultaneous measurement of thermogravimetric/differential thermal analyses, and solid state 13C-nuclear magnetic resonance (C-NMR).


RESULTS
The sulfate salt incorporated two types of lattice water to form a monohydrate or a trihydrate. Additional water could also be absorbed as channel water to expand the lattice structure. The activation energy for dehydration was very high, probably due to steric hindrance in the lattice structure. The nitrate salt incorporated only one water molecule per compound as the lattice water. The additional water was absorbed as channel water as observed for the sulfate salt. X-ray diffractograms showed little dependence on the salt type under the ambient condition. The hydration number was likely to be affected by the size of the counter acids.


CONCLUSIONS
The hygroscopicity of S-3578 salts was significantly altered by the salt type. The difference in the amount of the lattice water could be explained in terms of the difference in the molecular size of the counter acids.
Kawakami
Kohsaku
K
Developmental Research Laboratories, Shionogi & Co., Ltd., 12-4 Sagisu 5-chome, Fukushima-ku, Osaka, 553-0002, Japan. kohsaku_kawakami@merck.com
Ida
Yasuo
Y
Yamaguchi
Tohru
T
D000042:Absorption; D000465:Algorithms; D002152:Calorimetry, Differential Scanning; D002511:Cephalosporins / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D009682:Magnetic Resonance Spectroscopy; D012965:Sodium Chloride; D013818:Thermogravimetry; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
C471249:7-(2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido)-3-(1-(3-methylaminopropyl)-1H-imidazo(4,5-b)pyridinium-4-yl)methyl-3-cephem-4-carboxylate; D002511:Cephalosporins; D014867:Water; D012965:Sodium Chloride