QbD-driven optimization of ondansetron HCl via solid dispersion-loaded orodispersible films for chemotherapy-induced nausea and vomiting (CINV) management

Background This study involved improving solubility of ondansetron HCl (ODN-HCl) through solid dispersion followed by its inclusion into orodispersible films (ODFs) for improved chemotherapy-induced nausea and vomiting (CINV) management.Research design and methods Face-centered central composite design (FCCD) was used to optimize ODN-HCl solid dispersions through the combination of PEG 6000 and PVP K30 carriers. Solvent-evaporation method was used for SD preparation and characterized for solubility, particle size, zeta potential and polydispersity index. The optimized SD obtained integrated into ODFs of HPMC E50 matrix was evaluated for thickness, disintegration time, in-vitro drug release, and ex-vivo permeability.Results The FCCD yielded quadratic mathematical models (p < 0.0001) which indicated PEG 6000 and PVP K30 were key determinants for SD properties. Optimized SDs presented increased solubility levels of 4.5 times (0.2685 mg/ml compared to pure drug solubility of 0.0252 mg/ml) combined with lowered crystal formation that XRD and DSC measurements confirmed. The ODFs showed a quick disintegration time (