Enhanced oral bioavailability of quercetin by a new non‐aqueous self‐double‐emulsifying drug delivery system

Abstract

The present study investigated a new non‐aqueous self‐double‐emulsifying drug delivery system (SDEDDS) to enhance oral bioavailability of quercetin (QT), a drug with poor water solubility. The new formulation was prepared using a modified two‐step method and evaluated in vitro and in vivo. The optimized formulation consisted of oil‐in‐oil emulsions and hydrophilic surfactant that could spontaneously emulsify to oil‐in‐oil‐in‐water (O/O/W) double emulsions in the mixed aqueous gastrointestinal environment, with drugs mainly encapsulated in the inner oil phase of the double emulsions. Furthermore, the non‐aqueous QT‐SDEDDS exhibited sustained release of quercetin under conditions mimicking gastrointestinal tract, and gave significantly higher AUC and Cmax than did quercetin control suspension (p < 0.05). In particular, the AUC of the non‐aqueous QT‐SEDDS was about 5.22‐fold higher than that of drug control suspension, with an absolute bioavailability of 26.67%. The obtained results demonstrated that SDEDDS was successfully developed and could be a promising technique for improving the oral bioavailability of quercetin with low solubility.Practical applications:Conventional SDEDDS is mainly designed to encapsulate, protect, and release hydrophilic bioactive components. Hence, the new non‐aqueous SDEDDS could as a drug delivery system to encapsulate hydrophobic drug with low oral bioavailability. Pharmacokinetic studies have displayed increased relative bioavailability (more than fivefold) of QT‐SDEDDS compared to quercetin suspension in rats after oral administration, with an absolute bioavailability of 26.67%. The new formulation was prepared using a modified two‐step method, which is widespread and easy to handle. Furthermore, the used excipients are considered generally recognized as safe (GRAS) for addition to food and/or drug products. Regard to industrial production aspects, the non‐aqueous SDEDDS have the chance to be exploited as drug delivery system in commercial products. Hence, the non‐aqueous SDEDDS could be applicable delivery system for hydrophobic compounds with low oral bioavailability.(i) The new non‐aqueous QT‐SDEDDS could spontaneously emulsify to oil‐in‐oil‐in‐water (O/O/W) double emulsions upon mild agitation by dilution in aqueous media; and (ii) after oral administration in rats, the non‐aqueous SDEDDS displayed an absolute bioavailability of 26.67%, which was 5.22 times higher than that of quercetin control suspension.