(2015) Enhanced oral bioavailability of piperine by selfemulsifying drug delivery systems: invitro,invivo and insitu intestinal permeability studies, Drug Delivery, 22:6, 740-747, DOI: 10.3109/10717544.2014 AbstractThe main purpose of this work was to develop and evaluate a self-emulsifying drug delivery system (SEDDS) of piperine to enhance its solubility and bioavailability. The formulation was optimized by solubility test and ternary phase diagrams. Then physiochemical properties and in vitro release of SEDDS were characterized. In vivo pharmacokinetics study and in situ singlepass intestinal perfusion were performed to investigate the effects of SEDDS on the bioavailability and intestinal absorption of piperine. The optimized formulation was composed of ethyl oleate, Tween 80 and Transcutol P (3:5.5:1.5, w/w), with the level of the piperine reached 2.5% (w/w). The in vitro dissolution rates of piperine SEDDS were significantly higher than the self-prepared capsules. In vivo pharmacokinetic study showed C max1 , C max2 and area under the curve of piperine after oral administration of SEDDS in rats were 3.8-, 7.2-and 5.2-fold higher than the self-prepared capsules, respectively, and the relative bioavailability of SEDDS was 625.74%. The in situ intestinal absorption study revealed that the effective permeability and the effective absorption rate values of piperine for SEDDS were significantly improved comparing to solutions (p50.01). So SEDDS formulation could improve the oral bioavailability and intestinal absorption of piperine effectively.

Purpose: The present study was to formulate curcumin solid lipid nanoparticles (Cur-SLNs) with P-gp modulator excipients, TPGS and Brij78, to enhance the solubility and bioavailability of curcumin. Methods: The formulation was optimized by Plackett-Burman screening design and Box-Behnken experiment design. Then physiochemical properties, entrapment efficiency and in vitro release of Cur-SLNs were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of Cur-SLNs on the bioavailability and intestinal absorption of curcumin. Results: The optimized formulations showed an average size of 135.3 ± 1.5 nm with a zeta potential value of À24.7 ± 2.1 mV and 91.09% ± 1.23% drug entrapment efficiency, meanwhile displayed a sustained release profile. In vivo pharmacokinetic study showed AUC 0!t for Cur-SLNs was 12.27-folds greater than curcumin suspension and the relative bioavailability of Cur-SLNs was 942.53%. Meanwhile, T max and t 1/2 of curcumin for Cur-SLNs were both delayed comparing to the suspensions (p50.01). The in situ intestinal absorption study revealed that the effective permeability (P eff ) value of curcumin for SLNs was significantly improved (p50.01) comparing to curcumin solution. Conclusion: Cur-SLNs with TPGS and Brij78 could improve the oral bioavailability and intestinal absorption of curcumin effectively. KeywordsCurcumin, in situ intestinal absorption, oral bioavailability, P-glycoprotein, solid lipid nanoparticles History

Highlights(1) Tide amplitude decreases in the lowermost channel and tidal flats of the Yellow River Delta as river discharge increases.(2) The river discharge changes can reshape the shear front zone dynamics near the active Yellow River delta.(3) The barrier effect of the tidal shear front zone combined with strong longshore tidal currents significantly restrict the sediment dispersal and river mouth deposits.

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