Impacts of Polymeric Excipients on the Physicochemical Properties of Ritonavir Solid Dispersions

Amorphous solid dispersion (ASD) formulation prepared by solvent‑evaporation was employed to enhance the apparent solubility of the poorly water‑soluble drug ritonavir (RTV), a BCS Class IV compound widely used in HIV therapy. This study investigated the influence of polymeric excipients on ritonavir’s solid‑state form, apparent solubility, and dissolution behavior in ASDs prepared by the film casting–solvent evaporation. Thermal analysis and X‑ray diffraction examination (DSC, XRD) demonstrated a complete conversion of RTV from the crystalline to the amorphous state in most formulations, except the formulation containing 50% Copovidone, where total amorphization was not achieved. FTIR spectroscopy indicated non‑covalent interactions between RTV and polymers such as hydroxypropyl methylcellulose acetyl succinate (HPMCAS) and hydroxypropyl methylcellulose phtalate (HPMCP). Among the screened polymers, HPMCAS and Copovidone promoted the greatest improvement in apparent solubility, up to approximately 22-to-30-fold relative to crystalline RTV. Dissolution testing results exhibited that formulations containing HPMC P55, Eudragit L100‑55 and Eudragit E100 provided superior drug release. Increasing drug load in the ASD inversely influenced both the enhancement of apparent solubility and the ability to sustain supersaturation; high drug fractions in the solid dispersion promoted phase separation and surface precipitation of RTV, which impeded diffusion and reduced dissolution performance. Intrinsic dissolution and diffusion assays underscore the critical role of polymer selection in modulating molecular mobility and stabilizing the amorphous drug. Overall, findings in this study provide a scientific basis for applying amorphous solid dispersion to improve dissolution and enhance apparent solubility of ritonavir through appropriate polymer selection and drug loading optimization.