title: Moisture induced polymorphic transition of mannitol and its morphological transformation.
abstract: The effects of moisture on the polymorphic transition of crystalline mannitol were investigated. Mannitol has three polymorphic forms, and was classified as alpha, beta, and delta form, respectively, by Walter-Lévy (C.R. Acad. Sc. Paris Ser. C (1968) 267, 1779). The water uptake of delta form crystalline was greater than that of the beta form when each crystalline form was stored at 97%RH (25 degrees C). The different powder X-ray diffraction patterns obtained before and after humidification confirmed that a moisture induced polymorphic transition from the delta to beta form had occurred. Morphological changes were also observed with an increase in the specific surface area of the delta sample from 0.4 to 2.3 m(2)/g being found on exposure to humidity. Thus it was suggested that the observed higher hygroscopicity of the newly formed beta form arose from the gradual increase in the surface area with the polymorphic transition from the delta to beta form. When considering the mechanism of this polymorphic transition, the results from molecular modelling, cross-polarisation/magic angle spinning (CP/MAS) solid-state NMR spectra and scanning electron-micrographs suggest that water molecules act as a molecular loosener to facilitate conversion from delta to the beta form as a result of multi-nucleation.
authors.affiliation: Drug Delivery Group, The School of Pharmacy, University of Bradford, Bradford BD7 1DP, UK.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yoshinari
authors.forename: Robert T
authors.initials: RT
authors.lastname: Forbes
authors.forename: Peter
authors.initials: P
authors.lastname: York
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawashima
mesh_terms: D003460:Crystallization / Q000379:methods; D006813:Humidity; D008353:Mannitol / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D008353:Mannitol