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

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.

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Materials

RN was obtained as a gift sample from Hetero Pharmaceuticals Pvt. Ltd. Tween-80, Poloxamer 407 and Poloxamer 188 were procured from Hi-media laboratories Pvt.Ltd, Mumbai. Methanol and Chloroform (analytical grade) were procured from Merck, Mumbai. All other solvents and chemicals used for this work are of analytical grade.

Excipients mentioned in the study beside others: Compritol 888 ATO, Gelucire 39/1, soya lecithin

Chettupalli, A.K., Bukke, S.P.N., Rahaman, S.A. et al. Ritonavir loaded solid lipid nanoparticles for oral drug delivery and bioavailability enhancement. Discov Appl Sci 7, 58 (2025). https://doi.org/10.1007/s42452-024-06322-1

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