Aim To prepare a self-emulsifying microemulsion of 9-nitrocamptothecin （9-NC ME） for intravenous injection and investi- gation of its pharmacokinetic profiles in normal SD rats. Methods 9-NC ME was optimized in term...Aim To prepare a self-emulsifying microemulsion of 9-nitrocamptothecin （9-NC ME） for intravenous injection and investi- gation of its pharmacokinetic profiles in normal SD rats. Methods 9-NC ME was optimized in terms of droplet size and lack of drug precipitation following aqueous dilution using a pseudo-ternary phase diagram. Physicochemical properties of 9-NC ME were evaluated. 9-NC ME was intravenously administered via tail vein in healthy rats. Results A stable microemulsion was formulated consisted of soybean oil as oil phase, EPC/Tween-80 as emulsifier, and anhydrous ethanol as co-emulsifier. The droplets of the microemulsion were spherical shape with mean diameter of 38.3 ± 4.0 nm after 1：20 dilution with 5% glucose injection. The pharmacokinetic parameters of 9-NC ME after intravenous administration in rats were t1/2 of 0.97 ± 0.14 h, A UC0-8 of 372.77 ±49.62 ng·h·mL^-1 and MRT of 1.40 ± 0.21 h which were 1.4-fold, 1.65-fold, and 1.4-fold more than those of 9-NC solution （P〈0.01）. Conclusion The results suggested that 9-NC ME was a promising drug delivery system and it was expected to provide a novel 9-NC injection for cancer patients.展开更多
To enhance the oral absorption of the poorly water-soluble drug silybin, a self-microemulsifying drug delivery system （SMEDDS） composed of ethyl linoleate, Cremophor EL and PEG 400 for oral administration of silybin...To enhance the oral absorption of the poorly water-soluble drug silybin, a self-microemulsifying drug delivery system （SMEDDS） composed of ethyl linoleate, Cremophor EL and PEG 400 for oral administration of silybin was formulated, and its physicochemical properties and bioavailability of silybin were evaluated. The in vitro release of silybin from microemulsion and dispersion of silybin from SMEDDS were significantly faster than those from the commercial silybin hard capsule, respectively. The area under the drug concentration-time curve （AUC） and the mean maximum plasma level （Cmax） of the SMEDDS were remarkably greater than those of the hard capsule after oral administration to rats. The absorption of silybin formulated in SMEDDS exhibited a 2.3-fold increase in bioavailability as compared with the hard capsule. These results demonstrated that SMESDDS might be a useful drug delivery system for the oral delivery of the poorly water-soluble drug silybin.展开更多
Sorafenib is a novel antitumor drug,which is poorly absorbed in the gastrointestinal tract due to its low solubility in water.To improve the bioavailability of sorafenib,a self-microemulsifying drug delivery system(SM...Sorafenib is a novel antitumor drug,which is poorly absorbed in the gastrointestinal tract due to its low solubility in water.To improve the bioavailability of sorafenib,a self-microemulsifying drug delivery system(SMEDDS) formulation of sorafenib was prepared and its relative bioavailability in rats was evaluated.The blank SMEDDS was prepared from a mixture of ethyl oleate(oil phase,20%,w/w),Cremophol EL(surfactant,48%,w/w),PEG-400(co-surfactant,16%,w/w) and ethanol (co-surfactant,16%,w/w).Sorafenib was subsequently dissolved in the blank SMEDDS to obtain a sorafenib SMEDDS formulation with a final sorafenib concentration at 20 mg/mL.The particle size of the emulsified sorafenib SMEDDS was about 20-25 nm. Compared with sorafenib suspension,the prepared SMEDDS formulation exhibited no effect on the T_(max),but significantly increased the AUC,C_(max) and MRT and decreased the drug clearance.Most importantly,the oral bioavailability based on AUC_(0-72h) increased about 25 times after formulating sorafenib in SMEDDS.We concluded that SMEDDS could be a promising vesicle for the oral delivery of the poorly soluble antitumor drug sorafenib.展开更多
基金National Natural Science Foundation of China (GrantNo.30430760)the 985 projects (Phase II) of the State Key Labo-ratory of Natural and Biomimetic Drugs (Peking University, China).
文摘Aim To prepare a self-emulsifying microemulsion of 9-nitrocamptothecin （9-NC ME） for intravenous injection and investi- gation of its pharmacokinetic profiles in normal SD rats. Methods 9-NC ME was optimized in terms of droplet size and lack of drug precipitation following aqueous dilution using a pseudo-ternary phase diagram. Physicochemical properties of 9-NC ME were evaluated. 9-NC ME was intravenously administered via tail vein in healthy rats. Results A stable microemulsion was formulated consisted of soybean oil as oil phase, EPC/Tween-80 as emulsifier, and anhydrous ethanol as co-emulsifier. The droplets of the microemulsion were spherical shape with mean diameter of 38.3 ± 4.0 nm after 1：20 dilution with 5% glucose injection. The pharmacokinetic parameters of 9-NC ME after intravenous administration in rats were t1/2 of 0.97 ± 0.14 h, A UC0-8 of 372.77 ±49.62 ng·h·mL^-1 and MRT of 1.40 ± 0.21 h which were 1.4-fold, 1.65-fold, and 1.4-fold more than those of 9-NC solution （P〈0.01）. Conclusion The results suggested that 9-NC ME was a promising drug delivery system and it was expected to provide a novel 9-NC injection for cancer patients.
文摘To enhance the oral absorption of the poorly water-soluble drug silybin, a self-microemulsifying drug delivery system （SMEDDS） composed of ethyl linoleate, Cremophor EL and PEG 400 for oral administration of silybin was formulated, and its physicochemical properties and bioavailability of silybin were evaluated. The in vitro release of silybin from microemulsion and dispersion of silybin from SMEDDS were significantly faster than those from the commercial silybin hard capsule, respectively. The area under the drug concentration-time curve （AUC） and the mean maximum plasma level （Cmax） of the SMEDDS were remarkably greater than those of the hard capsule after oral administration to rats. The absorption of silybin formulated in SMEDDS exhibited a 2.3-fold increase in bioavailability as compared with the hard capsule. These results demonstrated that SMESDDS might be a useful drug delivery system for the oral delivery of the poorly water-soluble drug silybin.
基金The 973 Project(Grant No.2009CB930300)Scientific and Technological Major Special Project -"Significant Creation of New Drugs"(Grant No.2009ZX09310-001).
文摘Sorafenib is a novel antitumor drug,which is poorly absorbed in the gastrointestinal tract due to its low solubility in water.To improve the bioavailability of sorafenib,a self-microemulsifying drug delivery system(SMEDDS) formulation of sorafenib was prepared and its relative bioavailability in rats was evaluated.The blank SMEDDS was prepared from a mixture of ethyl oleate(oil phase,20%,w/w),Cremophol EL(surfactant,48%,w/w),PEG-400(co-surfactant,16%,w/w) and ethanol (co-surfactant,16%,w/w).Sorafenib was subsequently dissolved in the blank SMEDDS to obtain a sorafenib SMEDDS formulation with a final sorafenib concentration at 20 mg/mL.The particle size of the emulsified sorafenib SMEDDS was about 20-25 nm. Compared with sorafenib suspension,the prepared SMEDDS formulation exhibited no effect on the T_(max),but significantly increased the AUC,C_(max) and MRT and decreased the drug clearance.Most importantly,the oral bioavailability based on AUC_(0-72h) increased about 25 times after formulating sorafenib in SMEDDS.We concluded that SMEDDS could be a promising vesicle for the oral delivery of the poorly soluble antitumor drug sorafenib.
