Formulation development, optimization by Box-Behnken design, characterization, in vitro, ex-vivo, and in vivo evaluation of bosentan-loaded self-nanoemulsifying drug delivery system: A novel alternative dosage form for pulmonary arterial hypertension treatment

This study aimed to develop and optimize a self-nanoemulsifying drug delivery system (SNEDDS) of bosentan (BOS) to solve its poor oral bioavailability due to low water solubility. A pseudo-ternary phase diagram was created based on the solubility and emulsification studies. The major components of the formulation were selected as glyceryl monolinoleate (lipid), polyoxyl 40 hydrogenated castor oil (surfactant), and caprylocaproyl polyoxyl-8 glycerides (co-surfactant). The composition of BOS-SNEDDS was optimized using the Box-Behnken design (BBD) and then was characterized for various physicochemical properties. The in vitro dissolution, in vitro lipolysis, and ex-vivo permeability studies were performed and compared to SNEDDS and reference tablets. The fasted and fed state bioavailability of BOS-loaded SNEDDS was evaluated in Wistar rats (n = 6) compared to the reference. The prepared SNEDDS were thermodynamically stable with a droplet size of 17.11 nm, a polydispersity index of 0.180, and an emulsification time of