Hot Melt Extrusion Assisted Felodipine Loaded Liquid Crystal Precursor with Enhanced Solubility and Sustained Drug Release Characteristics

Abstract Glyceryl monooleate (GMO) forms cubic mesophase upon hydration with sustained drug release characteristics. However its stickiness and stiffness often creates processing challenges for preparation of formulations. Felodipine (FLD), BCS class II molecule was used as model drug. Thus objective of the current work was to increase manufacturing feasibility of GMO using polymer and to enhance the release of felodipine by preparing LC precursors using HME. HPMC E5 polymer was selected for processing of FLD. Batch optimization was done using 23 Factorial design. The prepared batches were characterized for DSC, FTIR, hot stage microscopy (HSM), plane polarized light microscopy (PPL), PXRD and in vitro dissolution studies. The processing of FLD using HME process showed amorphization as revealed by PXRD studies. DSC and HSM studies showed solubilization of FLD in the molten mass of GMO and HPMC E5 confirming formation of solid dispersion. PPL demonstrated formation of cubic LC phase by GMO upon hydration of prepared formulations. The optimized batch of felodipine showed significant improvement in the dissolution profile of FLD with extended release profile. HME assisted liquid crystal precursors could act as promising formulations for BCS II drugs requiring extended drug release profile with improved processing feasibility of GMO. GRAPHICAL ABSTRACT