Ethanol-assisted fabrication of Casein-Ritonavir amorphous dispersions

Abstract

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.