Investigation of thermal properties of glassy itraconazole: identificationof a monotropic mesophase

The purpose of the present work is the elucidation of two endothermic trans itions at 74 and 90 degreesC, respectively, observed during differential sc anning calorimetry of glassy itraconazole. Modulated temperature DSC (MTDSC ), hot-stage microscopy (HSM), HPLC and high temperature X-ray diffraction (HT-X ray) were used to examine the thermal properties of glassy itraconazo le. It was found that the preparation mode of the glass does not seem to in fluence the appearance of both endothermic transitions since they were pres ent during heating of glassy itraconazole which was prepared by cooling the melt or by rapid solvent evaporation of an itraconazole solution. These ob servations suggest that the appearance of the two endothermic transitions r equire the liquid state prior to glass formation. The transitions are not d ue to impurities in the starting material, nor are they caused by thermal d ecomposition. This was further confirmed by HPLC-analysis. HSM showed struc ture formation following cooling of the melt, at approximately 87 degreesC; cooling the product further showed a second change in optical contrast. HT -X ray confirmed and identified the formation of a nematic mesophase. The a ppearance of the two endothermic signals during scanning of glassy itracona zole points to the formation of a mesophase. Due to the nature of itraconaz ole, it appears as a chiral nematic phase of which the mobility is frozen i nto a glass upon cooling below 59 degreesC thereby impeding further crystal lization. (C) 2001 Elsevier Science B.V. All rights reserved.