College of Pharmacy, Yeungnam University, Gyungsan, Gyungbuk 712–749, South Korea.
Biol Pharm Bull. 2011;34(8):1179-86. doi: 10.1248/bpb.34.1179.
In this study, a novel liquid self-emulsifying drug delivery system (SEDDS) containing curcumin was formulated and further developed into a solid form by a spray drying method using Aerosil 200 as the solid carrier. The optimum liquid SEDDS consisted of Lauroglycol Fcc, Labrasol and Transcutol HP as the oil phase, the surfactant and the co-surfactant at a weight ratio of 15.0 : 70.8 : 14.2 (w/w/w), respectively. There was no difference in droplet size between the emulsions obtained from the liquid and solid forms of SEDDS. Solid state characterization of the solid SEDDS was performed by scanning electron micrograph (SEM), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD). The drug formulated in the solid SEDDS was quickly and completely dissolved within 5 min, both in 0.1 N HCl and phosphate buffer pH 6.8 dissolution media, whereas crude curcumin powder was significantly less dissoluble. The solid SEDDS formulation was stable for at least 3 months at 40°C with 75% relative humidity. After oral administration to rats, curcumin in the solid SEDDS resulted in significant improvement in in vivo absorption compared with that of curcumin powder. As the dose of curcumin formulated in solid SEDDS increased from 25 to 100 mg/kg, the C(max) and area under the drug concentration time curve (AUC) of curcumin were increased by 4.6 and 7.6 times, respectively. However, the over-proportional increase in the AUC in the higher dose group might be due to underestimation of AUC in the lower dose group. In conclusion, this solid SEDDS is a promising solid dosage form for poorly water-soluble curcumin.
在这项研究中,制备了一种含有姜黄素的新型液体自乳化药物传递系统(SEDDS),并进一步通过喷雾干燥法将其开发成固体形式,使用 Aerosil 200 作为固体载体。最佳液体 SEDDS 由 Lauroglycol Fcc、Labrasol 和 Transcutol HP 作为油相、表面活性剂和助表面活性剂组成,重量比为 15.0:70.8:14.2(w/w/w)。液体和固体 SEDDS 形式获得的乳液的粒径没有差异。通过扫描电子显微镜(SEM)、差示扫描量热法(DSC)和 X 射线粉末衍射(XRPD)对固体 SEDDS 的固体状态进行了表征。固体 SEDDS 中所包含的药物在 5 分钟内迅速且完全溶解,在 0.1N HCl 和磷酸盐缓冲液 pH6.8 的溶解介质中均如此,而粗姜黄素粉末的溶解度则明显较低。在 40°C 和 75%相对湿度下,固体 SEDDS 制剂至少稳定 3 个月。与姜黄素粉末相比,姜黄素在固体 SEDDS 中的口服给药可显著改善体内吸收。随着固体 SEDDS 中姜黄素的剂量从 25 增加到 100mg/kg,姜黄素的 Cmax 和药物浓度时间曲线下面积(AUC)分别增加了 4.6 倍和 7.6 倍。然而,在较高剂量组中 AUC 的不成比例增加可能是由于低估了较低剂量组中的 AUC。总之,这种固体 SEDDS 是一种很有前途的用于难溶性姜黄素的固体剂型。