Research On The Self-Emulsifying Drug Delivery System(SEDDS) Of Constituents Of Curcumin

Screening accessories which have good solubility for3ingredients in curcumin, drawing the three element phase diagram, using the D-optimal mixture design, with loading of3components, time of emulsifying and particle size as index, to optimize the prescription of SEDDS, and estimate it preliminary. The optimal prescription of SEDDS is Obleique CC497-Tween20-Transcutol P=0.16:0.54:0.30(m:m:m). The experiment achieved solubilization of SEDDS for multi-component simultaneously. Compared with bulk drug, which increased the solubility of BDMCur, DMCur and Cur in water20times,79times and217times, time emulsifying was7.0s, the average particle size was197.5nm, polydispersity index was29.0%, and Zeta potential was-20.22mV.With the perfusion in vivo intestinal, respectively, to determinate3components of curcumin in different intestine segments in rats and different concentrations of A%, Ka and Papp, and to explore the influence of P-gp inhibitor Vera Pammy hydrochloride, MRP2inhibitor probenecid and energy inhibitor2,4-dinitrophenol on the3components of curcumin in intestinal absorption.As a result, the absorption of BDMCur was better in duodenum but poor in the colon in rats; its intestinal absorption existed inhibitory concentration; P-gp substrate inhibitor verapamil hydrochloride and MRP2substrate inhibitor probenecid can significantly improve the intestinal absorption of A%, Ka, Papp value of BDMCur, which suggested that the mechanism of absorption of BDMCur may be the same of verapamil hydrochloride and probenecid; energy inhibitors can significantly reduce the intestinal absorption of A%, Ka, Papp values, there was energy-dependent effect on the absorption process.The absorption of DMCur existed saturation phenomenon; its A%, Ka, Papp value of absorption in duodenum was significantly higher than other bowels; P-gp substrate inhibitor verapamil hydrochloride and MRP2substrate inhibitor probenecid can significantly improve the intestinal absorption of A%, Ka, Papp value of DMCur (p <0.01),which suggested that it was the mechanism of absorption of DMCur may be the same of verapamil hydrochloride and probenecid; energy inhibitors significantly reduced the absorption of A%, Ka, Papp value of DMCur absorption, it said that there was energy-dependent effect on the absorption process.Inhibitory concentration existed in intestinal absorption of Cur; Cur had good absorption in the whole bowel, while absorption of A%, Ka, Papp value in duodenal was better than other bowels; high concentration of P-gp inhibitors significantly increased intestinal absorption of A%, Ka, Papp value of Cur; MRP2inhibitors can significantly increase the absorption of A%, Ka, Papp value of Cur; those suggested that the mechanism of absorption of Cur may be the same of verapamil hydrochloride and probenecid;energy inhibitors can significantly reduce the intestinal absorption of A%, Ka, Papp values, that said there was energy-dependent effect on the absorption process..In summary, BDMCur, DMCur and Cur are all easy to absorb. Active transportation process and passive diffusion mechanism may both exist in absorption of BDMCur, DMCur and Cur.