title: Factors influencing crystal growth rates from undercooled liquids of pharmaceutical compounds.
abstract: Amorphous forms of drugs are increasingly being used to deliver poorly water-soluble compounds. Therefore, understanding the magnitude and origin of differences in crystallization kinetics is highly important. The goal of this study was to better understand the factors that influence crystal growth rates from pharmaceutically relevant undercooled liquids and to evaluate the range of growth rates observed. The crystal growth rates of 31 drugs were determined using an optical microscope in the temperature region between the glass transition temperature (Tg) and the melting temperature (Tm). Thermodynamic parameters such as Tm, melting enthalpy, and Tg were determined using a differential scanning calorimeter (DSC). Selected viscosity values for the undercooled liquid were taken from the literature. The growth rates of the different compounds were found to be very different from each other with a variation of about 5 orders of magnitude between the fastest growing compounds and the slowest growing compounds. A comparison of the physicochemical properties showed that compounds that had fast crystal growth rates had smaller molecular weights, higher melting temperatures, lower melt entropies, lower melt viscosities, and higher crystal densities. Variations in the growth rates of the compounds could be rationalized to a large extent by considering the thermodynamic driving force for crystallization, the viscosity, and the entropy difference between the melt and undercooled liquid. This study therefore provides important insight into factors that may compromise the stability of amorphous pharmaceuticals.
authors: Department of Industrial and Physical Pharmacy, Purdue University , 575 Stadium Mall Drive, West Lafayette, Indiana 47907, United States.
authors: Niraj S
authors: NS
authors: Trasi
authors: Jared A
authors: JA
authors: Baird
authors: Umesh S
authors: US
authors: Kestur
authors: Lynne S
authors: LS
authors: Taylor
mesh_terms: D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004355:Drug Stability; D019277:Entropy; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D044367:Phase Transition; D044366:Transition Temperature; D014783:Viscosity
chemical_list: D004364:Pharmaceutical Preparations