Evaluating the non-isothermal crystallization behavior of organic molecules from the undercooled melt state using rapid heat/cool calorimetry

Abstract

Understanding the inherent crystallization tendency of organic molecules from the undercooled melt state is an important criterion to assess the glass-forming ability of a compound, and hence the ability to produce and maintain amorphous materials, an important area for drug delivery of poorly water-soluble therapeutics. The main objective of this study was to determine the critical cooling (R_crit,cool) and/or critical heating (R_crit,heat) rates to inhibit crystallization for a group of compounds with diverse chemistries and different crystallization tendencies. Compounds were cooled at various cooling/heating rates using a prototype rapid heat/cool (RHC) calorimeter, and crystallization (or lack thereof) from the undercooled melt was recorded. Results showed some compounds have very high crystallization tendencies [class (I–A)] from the undercooled melt state, with R_crit,cool rates above 1000 °C min⁻¹, while some compounds with low crystallization tendencies upon cooling [class (II) compounds] exhibited very high crystallization tendencies (R_crit,heat > 1000 °C min⁻¹) upon subsequent reheating from the amorphous state. The pronounced asymmetry observed between R_crit,cool and R_crit,heat rates for class (II) compounds was greatly reduced by rapidly quenching the compound from the melt state, preventing the formation of quenched-in nuclei during cooling and initiating crystallization upon reheating. The ability to apply controlled rapid heating and cooling rates to organic compounds thus provides useful insight into the crystallization tendency of organic compounds.