Exploration of theoretical and practical evaluation on Kollidon®SR matrix mediated amorphous filament extrusion of norfloxacin by melt extrusion

Abstract

The selection of an appropriate polymer for the preparation of amorphous solid dispersions via hot-melt extrusion (HME) deals with the study of various solid-state properties of drugs and polymers. Hence, before going to HME, it is necessary to have appropriate knowledge of drug-polymer miscibility, drug-polymer interactions, and Gibb's free energy of mixing for the respective drug-polymer system. In the present work, we evaluated the miscibility and interaction parameters between norfloxacin (NOR) and Kollidon®SR Powder (KSR-P). The solubility parameter approach, based on theoretical calculations, was performed as a preliminary step for the prediction of miscibility between NOR and KSR-P. A theoretical and experimental approach was used as a validation tool using Flory-Huggin's interaction parameter value determined using the melting point depression method. The effect of NOR loading on the interaction parameter was systemically predicted to construct a thermodynamic phase diagram and Gibb's free energy of mixing for the NOR and KSR-P binary systems for the preparation of amorphous filament extrudate. A temperature-composition phase diagram was used to predict the processing temperature at the respective NOR loading to obtain a homogenous amorphous extrudate. Further, the obtained extrudate was evaluated through dimension studies, NOR assay, DSC, XRD, ATR analysis, and release behaviour.