Hot Melted Amorphous Solid Dispersion of Ritonavir With <scp>PVPVA</scp> and Span 60: Physicochemical Characterization and In Vitro Assessment

ABSTRACT The therapeutic activity of ritonavir (RTV), an antiretroviral drug, is limited due to its poor aqueous solubility and permeability. Amorphous solid dispersion (ASD) by the hot melt technique emerges as an outstanding approach for the improvement of bioavailability of poorly aqueous soluble drugs. We report here an ASD of RTV and PVPVA (Plasdone‐S630) with surfactant Span‐60 as permeation enhancer using the hot melt technique. The optimized ASD (HMRF4) showed improved solubility and permeability compared with native RTV. The results of FT‐IR, DSC, SEM, and powder XRD analysis showed that crystalline RTV was molecularly dispersed in carrier polymer and transformed into the amorphous state. Furthermore, the RTV‐ASD exhibits a favorable safety profile and excellent biocompatibility when tested in THP‐1 monocytes. Moreover, in vitro dissolution studies revealed that the hot melt RTV‐ASD tablet formulation achieved 95.24% drug release within 2 h in 0.1 N HCl medium, compared to only 75.22% release from the native RTV tablet under identical conditions. Similarly, 66.30% of the drug was released from the RTV‐ASD tablet in phosphate buffer pH 6.8, whereas from the native RTV, only 9.53% was released after 3 h. There was an improvement in RTV dissolution after the addition of surfactant in pH 6.8 dissolution media; however, the RTV‐ASD showed better performance. Overall, the developed formulation exhibited significant improvements in aqueous solubility, permeability, and drug release, providing promising implications for enhancing the bioavailability of RTV.