Moisture induced polymorphic transition of mannitol and its morphological transformation

• Published in: International journal of pharmaceutics Vol. 247; no. 1; pp. 69 - 77
• Main Authors: Yoshinari, Tomohiro, Forbes, Robert T, York, Peter, Kawashima, Yoshiaki
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 24-10-2002; Elsevier
• Subjects: Biological and medical sciences; Crystallization - methods; General pharmacology; Humidity; Hydrogen-bonding; Mannitol; Mannitol - chemistry; Medical sciences; Moisture; Morphological transformation; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polymorphic transition; X-Ray Diffraction - methods; Polymorphic transition; Hydrogen-bonding; Moisture; Morphological transformation; Mannitol; Crystalline material; Solid state; Structure stability; Pharmaceutical technology; Water content; Drug adjuvant; Polymorphic transformation; Physical properties; Physicochemical properties; Physical structure
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(02)00380-0

The effects of moisture on the polymorphic transition of crystalline mannitol were investigated. Mannitol has three polymorphic forms, and was classified as α, β, and δ form, respectively, by Walter-Lévy (C.R. Acad. Sc. Paris Ser. C (1968) 267, 1779). The water uptake of δ form crystalline was greater than that of the β form when each crystalline form was stored at 97%RH (25
°C). The different powder X-ray diffraction patterns obtained before and after humidification confirmed that a moisture induced polymorphic transition from the δ to β form had occurred. Morphological changes were also observed with an increase in the specific surface area of the δ 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 β form arose from the gradual increase in the surface area with the polymorphic transition from the δ to β 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 δ to the β form as a result of multi-nucleation.