Dr DEVELOPMENT OF POSACONAZOLE DELAYED RELEASE FORMULATION FOR MUCORMYCOSIS BY HOT MELT EXTRUSION USING QBD APPROACH

Abstract

Amorphous solid dispersion (ASD) by hot-melt extrusion (HME) is an industrially feasible approach to overcome the solubility and bioavailability limitations of poorly soluble active pharmaceutical actives. The creation of HME-based ASDs was significantly impacted by the implementation of Quality by Design (QbD). The objective of the study was to develop an ASD of posaconazole for the effective management of mucormycosis. The impact of change in levels of extra granular materials were identified as critical quality attributes (CQA's) for the development of delayed release tablet. A 23 full factorial design was employed to study the impact of independent variables HPMCAS (X1), HPC(X2) and CCS (X3) as CQA’s on the dependent variables such as hardness (Y1) and Disintegration Time (Y2) and % Drug release (Y3). The design was analyzed by using ANOVA by using MINITAB software. The influence of the extra granular components on the dissolution of tablet was closely evaluated while finalizing the optimized batch. The extrudes were also evaluated by FTIR, XRD and DSC analysis which confirmed the purity and in-situ conversion from crystalline to amorphous form of
the drug. Systematic development of a bioavailable and stable ASD of posaconazole was achieved by studying the CQA’s at different levels by using the QbD and from the stability data, the optimized batch F4 was found to be stable up to 3 months at accelerated conditions40°C/75%Rh.