Abstract
The aim of this study was to show that atomic force microscopy (AFM) can be used to obtain mechanistic and kinetic information about the process of moisture‐induced surface crystallization of single particles of amorphous lactose. Completely amorphous lactose particles were prepared by spray‐drying a solution of α‐lactose monohydrate, and moisture‐induced crystallization was monitored for a bed of particles by microcalorimetry and for single particles by AFM. From the AFM images it was found that crystallization of the surface of single particles can be described in terms of a sequence of three events: an initial smoothening of the surface, formation of crystalline nanostructures dispersed in amorphous material, and growth of these structures to a complete crystalline surface. The surface roughness parameter rugosity was used to estimate the fraction crystalline surface, and the growth kinetics were found to obey the JMAK equation. The fraction crystalline surface at different times could also be estimated by determining the growth rate of individual crystals. It was concluded that AFM offers a unique means of visualizing the process of moisture‐induced surface crystallization of amorphous particles and enables mechanistic and kinetic information about the process to be extracted. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:29–37, 2004
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