POLYMORPHIC STABILITY EVALUATION OF DARUNAVIR AND RITONAVIR IN FIXED DOSE DRUG COMBINATION PRODUCT BY X-RAY DIFFRACTION AND DIFFERENTIAL SCANNING CALORIMETRY TECHNIQUES

Abstract

Evaluation of polymorphism for active ingredients and its stability during manufacturing and storage is a critical task for pharmaceutical firms. For solubility enhancement of ritonavir, hot melt extrusion process was selected through conversion of commercially available crystalline form to amorphous. XRD method (with normal and slow scan) and DSC method was considered for polymorphic evaluation in tablet formulation comprising darunavir 800 mg and ritonavir 100 mg. Specificity and precision of XRD method was justified by no interference of placebo and 5.6% RSD, respectively. The observed correlation coefficient of 0.9991 and average recovery of 98.7% (range 91.5 to 105.1) depicts linearity and recovery power of developed method. Studied DSC method shows exotherm for ritonavir crystalline form II at 127.4 °C and darunavir ethanolate at 105.7 °C, which were specific and sensitive to assess polymorphic form of available drug substances in ritonavir blend as well as in tablet formulation during release and stability period.