Methods of amorphization and investigation of （的无定形化和调查方法）.pdf

Acta Pharm. 63 (2013) 305–334 Review DOI: 102478/acph-2013-0026 Methods of amorphization and investigation of the amorphous state TOMA@ EINFALT* The amorphous form of pharmaceutical materials repre- ODON PLANIN[EK KLEMEN HROVAT sents the most energetic solid state of a material. It pro- vides advantages in terms of dissolution rate and bio- University of Ljubljana, Faculty of availability. This review presents the methods of solid- Pharmacy, 1000 Ljubljana, Slovenia -state amorphization described in literature (supercooling of liquids, milling, lyophilization, spray drying, dehy- dration of crystalline hydrates), with the emphasis on milling. Furthermore, we describe how amorphous state of pharmaceuticals differ depending on the method of preparation and how these differences can be screened by a variety of spectroscopic (X-ray powder diffraction, solid state nuclear magnetic resonance, atomic pairwise distribution, infrared spectroscopy, terahertz spectros- copy) and calorimetry methods. Keywords: amorphous solid preparation, crystallinity, Accepted April 26, 2013 spectroscopy, calorimetry The existen