Sildenafil (SLD) is employed for the management of erectile dysfunction and pulmonary arterial hypertension. It exhibits meagre water solubility and is available in the form of citrate salt hydrate to improve the solubility. However, it still exhibits moderate solubility, high first-pass metabolism, resulting in very less oral bioavailability. The present study demonstrates the preparation of self-nanoemulsifying drug delivery system for augmenting the oral bioavailability of SLD. Oleic acid and Capmul MCM C8 blend (oil phase), Cremophor® RH40 (surfactant), and Labrafil® M1944 CS (cosurfactant) were selected as main constituents for making liquid preconcentrate based on the solubility and emulsification study. The preconcentrate upon dilution and emulsification showed droplet size 52.03 ± 13.03 nm, PDI 0.143 ± 0.028, and % transmittance was 99.77 ± 1.86% with SLD load of 40 mg/g of formulation. The prepared formulation was further assessed for stability, in vitro release, Caco-2 cell uptake, and in vivo pharmacokinetic performance. SLD-SNEDDS formulation was found to be robust in terms of stability against several folds dilution in the gastrointestinal tract (GIT), freeze-thaw cycles, and had a storage stability of 3 months at 4 °C and 25 °C. SLD-SNEDDS showed ~4.7-fold and ~5-fold increase in time- and concentration-dependent cellular uptake as against SLD cultured with Caco-2 cells. In vivo pharmacokinetic study revealed ~5.8- and ~2.5-fold increase in AUC0-∞ values in case of SLD-SNEDDS as against SLD suspension and SLD citrate solution, respectively.
Keywords: Caco-2; Nanoemulsion; Oral bioavailability; Sildenafil; Solubility.
© 2022. Controlled Release Society.