Enhancing drug solubilization using a surface-modified edible biopolymer through hot melt extrusion: A design space methodology.

This study investigates the use of an octenylsuccinate-modified dendrimer-like biopolymer (OS-DLB) as a carrier matrix in the formulation of biodendrimeric solid dispersions (BDSDs) using hot melt extrusion (HME). Ibuprofen (IBU) and griseofulvin (GSF) were selected as model compounds due to their poor aqueous solubility - one limited by its hydrophobicity and the other by its strong crystal lattice, respectively. This study demonstrates that the BDSD formulation can significantly enhance the dissolution rates of the model compounds through a parallel liquid phase equilibrium, while retaining their predominantly crystalline state. Across the 13 runs, IBU BDSDs showed a rapid initial dissolution with inter-batch variability converging by 60 min, whereas GSF BDSDs displayed wider divergence. IBU also underwent some loss of crystallinity due to its miscibility with PLX, a phenomenon not observed for GSF. Using a design space approach, which integrates experimental design, multivariate prediction models, and response surface modeling, the findings reveal that processing temperature, residence time, and screw speed are important factors affecting the dissolution and crystallinity of the BDSDs. The extent of their influence, however, varies depending on the crystal lattice energy and hydrophobicity of the model compounds. The HME design space for producing GSF BDSDs is less sensitive to processing variables than that for IBU BDSDs. For GSF, uniform dispersion of PLX throughout the BDSDs and preservation of OS-DLB structure are key to improving dissolution. In contrast, limited molecular distribution of PLX is crucial to producing IBU BDSDs with high crystallinity.