Ritonavir loaded solid lipid nanoparticles for oral drug delivery and bioavailability enhancement
Ananda Kumar Chettupalli, Sarad Pawar Naik Bukke, Shaik Abdul Rahaman, Aziz Unnisa, Madhumitha Adepu, Marati Kavitha, Malakapogu Ravindra Babu, Bayapa Reddy Narapureddy, Hope Onohuean
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