Ethanol-assisted fabrication of Casein-Ritonavir amorphous dispersions

The study investigates the impact of ethanol content and temperature on the formation of casein-ritonavir amorphous dispersions, aiming to enhance the drug's effective solubility and delivery. Ritonavir, a poorly water-soluble crystalline antiviral medication, was combined with casein in aqueous ethanol solutions ranging from 0 to 60 % v/v ethanol and 60°C. Solubility tests revealed a sharp increase in ritonavir solubility in 50% ethanol, highlighting that reduced solvent polarity facilitates drug dispersion. After solvent removal, thermal analysis confirmed ritonavir-casein interaction leading to the formation of ritonavir amorphous dispersions. Microstructural analysis revealed a significant decrease in crystalline peaks and spectral shifts in the amide regions, particularly in ethanol-treated samples, indicating changes in the local microenvironment and noncovalent molecular associations of ritonavir within the casein matrix. Zeta potential measurements showed a consistent increase in negative surface charge (-45 mV to -60 mV) with increasing ethanol content during complex fabrication, indicating changes in surface charge characteristics and electrostatic dispersion stability. Therefore, these findings support the formation of stable, amorphous casein-ritonavir complexes with improved solubility and potential for oral delivery applications.