Formulation and evaluation of self-nanoemulsifying drug delivery system of brigatinib: Improvement of solubility, in vitro release, ex-vivo permeation and anticancer activity

The aim of this study was to develop a novel self-nanoemulsifying drug delivery system (SNEDDS) of brigatinib, a poorly soluble anticancer drug, so as to improve its solubility, in vitro release, ex-vivo permeation and anticancer activity. Components of SNEDDS were screened on the basis of maximum solubility of brigatinib. Oleic acid, Tween 20 & diethylene glycol monoethylether were selected as oil phase, emulsifier and co-solvent respectively. Various brigatinib-SNEDDS were developed by spontaneous, low energy, simple mixing method. Developed SNEDDS were optimized on the basis of self-emulsifying capacity, globule size, size distribution, thermodynamic stability and capacity to solubilize maximum amount of brigatinib. The optimized SNEDDS was characterized for physicochemical evaluations such as viscosity, conductivity, pH and refractive index in addition to morphological evaluation of globule size and shape by transmission electron microscopy. The optimized SNEDDS exhibited approximately 205-fold enhancement in the saturation solubility of the brigatinib that resulted in improved in vitro release of drug from SNEDDS as compared to pure drug (P < 0.01). The ex-vivo permeation of brigatinib-SNEDDS across rat intestinal sacs was also improved as compared to pure drug (P < 0.01). The cytotoxic activity of brigatinib-SNEDDS against A549 human lung cancer cell lines during MTT assay were significantly improved as compared to pure brigatinib probably due to improved permeability of the SNEDD loaded brigatinib.