Ritonavir loaded solid lipid nanoparticles for oral drug delivery and bioavailability enhancement

Abstract

Abstract Background Ritonavir is an anti-retroviral protease inhibitor to treat HIV, AIDS infections. Methods The RN-SLNs were prepared by using hot homogenization followed ultrasonication method and optimized by using a two-factor, three-level central composte design (CCD). The independent variables were selected as phospholipids (X1) and type of surfactants (X2), whereas the dependent variables were chosen as percent entrapment efficiency (%EE) (Y1), size of the particle (Y2), and percent cumulative drug release (Y3). Further, the formulated R-SLNs were characterized and in vitro drug release studies were performed. The optimized R-SLNs were subjected to in vivo pharmacokinetic studies. Results The solid lipid soya leccithin showed the maximum solubility of RN (103.34 mg/g) compared to stearic acid (81.44 mg/g), glyceryl monostearate (67.21 mg/g), Gelucire 39/1 (44.22 mg/g), and Compritol 888 ATO (31.23 mg/g). Further, the surfactant blend (Tween 80: Poloxamer 188 (8:2)) showed the maximum entrapment efficiency and was the most suitable surfactant. The optimized RN-SLN formulation showed a particle size of 265.06 ± 5.12 nm, % EE of 86.2 ± 3.16 and cumulative drug release of 94.8 ± 0.16%. In addition, in-vitro drug release studies confirmed a biphasic release pattern, and followed Higuchi’s model. The in vivo pharmacokinetic studies showed an increase in bioavailability by 4.3 folds as compared to marketed formulation. Conclusions The optimized RN-SLNs significantly enhanced the solubility and bioavailability of RN. The results of the present study can become a promising platform for the enhancement of oral bioavailability by novel nano carriers. Graphical abstract

Keywords

• Ritonavir
• Solid-lipid nanoparticles
• Absorption
• Bioavailability
• Drug-delivery