Mahlin Denny, Berggren Jonas, Alderborn Göran, Engström Sven
Department of Pharmacy, Uppsala University, Box 580, SE-751 23 Uppsala, Sweden.
J Pharm Sci. 2004 Jan;93(1):29-37. doi: 10.1002/jps.10503.
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 alpha-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.
本研究的目的是表明原子力显微镜（AFM）可用于获取有关无定形乳糖单颗粒水分诱导表面结晶过程的机理和动力学信息。通过喷雾干燥α-乳糖一水合物溶液制备完全无定形的乳糖颗粒，并通过微量量热法监测颗粒床的水分诱导结晶，通过AFM监测单颗粒的水分诱导结晶。从AFM图像中发现，单颗粒表面的结晶可以用三个事件的序列来描述：表面的初始平滑化、分散在无定形材料中的晶体纳米结构的形成以及这些结构生长为完整的晶体表面。表面粗糙度参数糙度用于估计晶体表面分数，发现生长动力学符合JMAK方程。不同时间的晶体表面分数也可以通过确定单个晶体的生长速率来估计。得出的结论是，AFM提供了一种独特的手段来可视化无定形颗粒水分诱导表面结晶的过程，并能够提取有关该过程的机理和动力学信息。
