Characterization and crystal structure of D-mannitol hemihydrate

Characterization and crystal structure of D-mannitol hemihydrate
September 2004
By Cletus Nunes, Raj Suryanarayanan, Cristian E. Botez, Peter W. Stephens
Journal of Pharmaceutical Sciences, Volume 93, Issue 11, Date: November 2004, Pages: 2800-2809
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Abstract
The objectives of this study were (i) to isolate and characterize mannitol hydrate, and (ii) to solve its crystal structure from high-resolution synchrotron X-ray powder diffraction data. Mannitol hydrate was prepared by freeze-drying aqueous mannitol solutions (5% w/v) under controlled conditions. X-ray powder diffractometry, differential scanning calorimetry, and thermogravimetric analyses indicated that mannitol exists as a hemihydrate (C6H14O6 ? 0.5H2O). Synchrotron data were collected on the X3B1 beamline at the National Synchrotron Light Source. The simulated annealing program PSSP was used to solve the structure, which was subsequently refined by Rietveld analysis using the program package GSAS. The compound crystallizes in space group P1, with a = 9.8963 ?, b = 10.5424 ?, c = 4.7860 ?, = 102.589?, = 86.092?, and = 116.079?. The unit cell contains two dissimilar D-mannitol molecules and one water molecule, forming a hydrogen bonding pattern significantly different from that seen in the anhydrous polymorphs. ? 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2800-2809, 2004