Isothermal And Non-Isothermal Crystallization Kinetics Of Amorphous Ketoconazole

摘要

Amorphous pharmaceuticals are of manifold importance owing to their increased dissolution propertiesand greater bioavailability. Ketoconazole is an oral and topical antifungal drug which has moderate oralabsorption in the crystalline phase. Crystalline ketoconazole is sparingly soluble drug thus limiting itsdissolution properties. Amorphous ketoconazole if suitably formulated can be used with enhancedtherapeutic efficacy. An extensive study on the crystallization kinetics of conversion of amorphousketoconazole to crystalline form is done. In this study the non-isothermal kinetics of recrystallization ofamorphous ketoconazole was investigated using Differential Scanning Calorimetric Technique. Theamorphous phase was confirmed by PXRD studies. It was found that varying the amount of ketoconazoleseed crystals didn't affect the activation energy of amorphous ketoconazole to change from amorphous tothe crystalline phase. The value of activation energy was also found to be very high in the isothermalstudy emphasizing that ketoconazole amorphous is a stable glass. The glass stability value (Kgl) wasdetermined to range from 2-3 for amorphous ketoconazole. The stability of the glass decreased withincrease in the amount of seed crystals. The Avrami exponent values for amorphous ketoconazoledetermined by the non-isothermal studies corroborated that a one-dimensional linear crystallizationoccurred when amorphous ketoconazole transformed to the crystalline phase.