Rashid Rehmana, Kim Dong Wuk, Yousaf Abid Mehmood, Mustapha Omer, Park Jong Hyuck, Yong Chul Soon, Oh Yu-Kyoung, Youn Yu Seok, Kim Jong Oh, Choi Han-Gon
College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, South Korea.
College of Pharmacy, Yeungnam University, Gyeongsan, South Korea.
Int J Nanomedicine. 2015 Sep 30;10:6147-59. doi: 10.2147/IJN.S91216. eCollection 2015.
The objective of this study was to compare the physicochemical characteristics, solubility, dissolution, and oral bioavailability of an ezetimibe-loaded solid self-nanoemulsifying drug delivery system (SNEDDS), surface modified solid dispersion (SMSD), and solvent evaporated solid dispersion (SESD) to identify the best drug delivery system with the highest oral bioavailability.
For the liquid SNEDDS formulation, Capryol 90, Cremophor EL, and Tween 80 were selected as the oil, surfactant, and cosurfactant, respectively. The nanoemulsion-forming region was sketched using a pseudoternary phase diagram on the basis of reduced emulsion size. The optimized liquid SNEDDS was converted to solid SNEDDS by spray drying with silicon dioxide. Furthermore, SMSDs were prepared using the spray drying technique with various amounts of hydroxypropylcellulose and Tween 80, optimized on the basis of their drug solubility. The SESD formulation was prepared with the same composition of optimized SMSD. The aqueous solubility, dissolution, physicochemical properties, and pharmacokinetics of all of the formulations were investigated and compared with the drug powder.
The drug existed in the crystalline form in SMSD, but was changed into an amorphous form in SNEDDS and SESD, giving particle sizes of approximately 24, 6, and 11 µm, respectively. All of these formulations significantly improved the aqueous solubility and dissolution in the order of solid SNEDDS ≥ SESD > SMSD, and showed a total higher plasma concentration than did the drug powder. Moreover, SESD gave a higher area under the drug concentration time curve from zero to infinity than did SNEDDS and SMSD, even if they were not significantly different, suggesting more improved oral bioavailability.
Among the various formulations tested in this study, the SESD system would be strongly recommended as a drug delivery system for the oral administration of ezetimibe with poor water solubility.
本研究的目的是比较载有依折麦布的固体自纳米乳化药物递送系统（SNEDDS）、表面改性固体分散体（SMSD）和溶剂蒸发固体分散体（SESD）的物理化学特性、溶解度、溶出度和口服生物利用度，以确定具有最高口服生物利用度的最佳药物递送系统。
对于液体SNEDDS制剂，分别选用辛酸癸酸甘油三酯、聚氧乙烯蓖麻油EL和吐温80作为油相、表面活性剂和助表面活性剂。基于减小的乳液尺寸，使用伪三元相图绘制纳米乳液形成区域。通过用二氧化硅喷雾干燥将优化的液体SNEDDS转化为固体SNEDDS。此外，使用喷雾干燥技术，加入不同量的羟丙基纤维素和吐温80制备SMSD，并根据其药物溶解度进行优化。SESD制剂采用与优化后的SMSD相同的组成制备。研究了所有制剂的水溶性、溶出度、物理化学性质和药代动力学，并与药物粉末进行比较。
药物在SMSD中以结晶形式存在，但在SNEDDS和SESD中变为无定形形式，粒径分别约为24、6和11 µm。所有这些制剂均显著提高了水溶性和溶出度，顺序为固体SNEDDS≥SESD＞SMSD，并且显示出比药物粉末更高的总血浆浓度。此外，SESD在从零到无穷大的药物浓度时间曲线下的面积比SNEDDS和SMSD更高，即使它们之间没有显著差异，这表明口服生物利用度有更大改善。
在本研究测试的各种制剂中，强烈推荐SESD系统作为口服给药难溶性依折麦布的药物递送系统。
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