Tocofersolan micelles for improved solubility and oral bioavailability of ritonavir

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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.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.