PURPOSE: 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.
PURPOSE: 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.
Authors: Zedong Dong; Jonathon S Salsbury; Deliang Zhou; Eric J Munson; Steve A Schroeder; Indra Prakash; Sergey Vyazovkin; Charles A Wight; David J W Grant Journal: J Pharm Sci Date: 2002-06 Impact factor: 3.534