Quality by Design Driven Development and Optimization of Hot Melt Extruded Amorphous Solid Dispersions for Enhanced Dissolution of a Poorly Soluble BCS Class IV Drug
Year: 2026
Type: article
Abstract: Low solubility and membrane permeability in the aqueous environment are the primary impediments to the oral bioavailability of BCS Class IV drug candidates. Poor dissolution and variable absorption have been the challenges. The intent of the current study was to optimize the formulation of amorphous solid dispersions (ASDs) of a poorly soluble BCS Class IV drug using HME technology to augment dissolution performance. The saturation solubility studies showed very low solubility of the drug in aqueous and several dissolution media, thus indicating the need for a suitable formulation approach. Various hydrophilic polymers, including Kollidon® VA64, Soluplus®, Kollidon® 30 and PEG 6000, were investigated using solvent evaporation and hot melt extrusion methods. Of all the investigated carriers, Kollidon® VA64 exhibited the highest solubility enhancement, particularly in HME formulations. To optimize the polymer concentration, a QbD-based approach using a full factorial experimental design was employed, and the optimized formulation was evaluated and compared with the other formulations. This formulation exhibited a considerably improved drug release than the pure drug, and the dissolution profile was found to be comparable with the marketed formulation (F2 = 74.47). The effect of polymer concentration on enhancement of dissolution was well modelled (R² = 0.98294), and the model was statistically meaningful (p = 0.0010). Solid state characterization was performed using DSC and XRay Diffraction (XRD). The DSC thermograms depicted an absence of the characteristic melting endotherm of the drug and the XRD patterns depicted a decrease in the diffraction peaks of the crystalline form suggesting that the crystalline form of the drug was converted to amorphous form due to the molecular dispersion of the drug into the polymeric matrix during hot melt extrusion processing. Conclusively, the results of this study suggest that HME-based ASD technology, when supported by QbD optimization, is a viable and scalable approach to improve dissolution behaviour for poorly soluble BCS Class IV drugs.
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W7167596566