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

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.