Stable amorphous solid dispersions of fenofibrate using hot melt extrusion technology: Effect of formulation and process parameters for a low glass transition temperature drug.

Development of stable amorphous solid dispersions (ASDs) for a low glass transition temperature (Tg) drug is a challenging task. The physico-chemical properties of the drug and excipients play a critical role in developing stable ASDs. In this study, ASDs of poorly soluble fenofibrate, a drug with a low Tg, were formulated using hydroxy propyl methylcellulose acetate succinate (HPMCAS) via hot melt extrusion (HME). The feasible processing conditions were established at varying drug loads and processing temperatures. The prepared ASDs were characterized for crystallinity using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Fourier transform-infrared spectroscopy was performed to study the potential interactions. DSC and PXRD studies confirmed the amorphous state of fenofibrate in the prepared ASDs. A discriminative in vitro dissolution method was established to study the impact of HPMCAS grades on dissolution profile. The dissolution parameters such as dissolution efficiency, initial dissolution rate and mean dissolution rate, suggested improved dissolution characteristics compared to pure fenofibrate. Accelerated stability studies at 40 °C/75% RH showed preservation of the amorphous nature of fenofibrate in formulations with 15% drug load and in vitro drug release studies indicated similar release profiles (f2 >50). This study provides an insight into the formulation and processing of ASDs for poorly soluble drugs with low Tg.