Tocofersolan micelles for improved solubility and oral bioavailability of ritonavir

This study focused on the development of ritonavir-loaded tocofersolan polymeric micelles (RV-TCF-PM) to enhance the solubility and oral bioavailability of ritonavir. It is a BCS Class II HIV-1 protease inhibitor with low and variable oral bioavailability due to poor aqueous solubility, P-glycoprotein efflux, and extensive protein binding. RV-TCF-PMs were prepared using the thin-film hydration method and optimized through in vitro characterization and an in vivo pharmacokinetic study in rabbits. The optimized formulation (RV5) exhibited a particle size of 93.81 nm, polydispersity index of 0.170, and zeta potential of −23.8 mV, indicating good stability and uniformity. High entrapment efficiency (97.76 ± 1.34%) and drug loading (19.54 ± 1.53%) were achieved. Successful drug encapsulation was confirmed by DSC and PXRD analyses, while TEM revealed spherical micelles. In vitro drug release studies of RV-TCF-PMs demonstrated a significantly improved dissolution profile, with 80.18 ± 1.09% drug release within 18 h compared to 27.96 ± 1.35% from the ritonavir suspension. Oral administration of RV-TCF-PMs in rabbits resulted in a 2.77-fold enhancement in relative oral bioavailability. Overall, the findings suggest that tocofersolan-based polymeric micelles represent a promising approach to improve the oral delivery and therapeutic performance of ritonavir in HAART therapy.