Introduction Although the delivery of therapeutic compounds through an oral route is the most convenient route of administration exhibiting high patient compliance (1), in some cases, there are several challenges for the development of an oral drug delivery system which exerts appropriate bioavailability, pharmacokinetic profile, and suitable therapeutic outcomes (2-4). Poor aqueous solubility and low dissolution rates are among the major problems that are associated with the preparation of an oral drug delivery system containing a lipophilic drug (5). Moreover, due to high tendency for liver uptake and consequent metabolism, some drugs exhibit high first-pass metabolism which can lead to the inactivation of drugs immediately after absorption from intestinal epithelia into the portal vein. Another challenge for oral drug delivery is the expression and distribution of P-glycoproteins (P-gp) across the intestinal epithelium, causing the development of multi-drug resistance and low bioavailability due to the intestinal efflux of the absorbed drugs (6). Self-nanoemulsifying drug delivery systems (SNEDDS) are the isotropic mixtures of the oil, surfactant, and cosurfactant incorporating therapeutic compounds. After the dilution of SNEDDS with gastro-intestinal (GI) fluids, thermodynamically stable oil-in-water (o/w) nanodroplets can be formed spontaneously following gentle agitation provided from GI motility (7). Forgiarini et al (8) reported that stable nano-emulsions with a droplet size of approximately 50 nm can be prepared by the addition of appropriate amounts of water into the mixture of the oil and surfactant under gentle agitation. Lipophilic compounds, representing low aqueous solubility, have high potency to incorporate to the internal oily phase of nano-droplets. Recently, researchers have
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