Zheng Wen-wu, Zhao Ling, Wei Yu-meng, Ye Yun, Xiao Shun-han
Department of Cardiology, People's Hospital of Luzhou, No. 61 Zhongxiao Road, Luzhou, Sichuan Province, P. R. China.
Chem Pharm Bull (Tokyo). 2010 Aug;58(8):1015-9. doi: 10.1248/cpb.58.1015.
The objective of this study was to develop and evaluate nanoemulsion system for transdermal delivery of granisetron hydrochloride. Pseudo-ternary phase diagram was constructed to ascertain the concentration range of components of nanoemulsion composed of isopropyl myristate (IPM) as an oil phase, tween 85 as surfactant, ethanol as cosurfactant, water as aqueous phase. The effects of the content of IPM as an oil phase and n-methyl pyrrolidone (NMP) as transdermal enhancer on rat skin permeation of granisetron hydrochloride nanoemulsion were studied in vitro. The results showed that the mean particle size of nanoemulsion ranged from 50.4+/-1.5 to 82.4+/-0.9 nm with homogeneous size distribution. The resulted optimum formulation composed of 2.5% granisetron hydrochloride, 4% IPM, 40% tween 85/ethanol (1 : 1) and 10% NMP showed that the skin permeation rate was the highest (85.39+/-2.90 microg/cm(2)/h) and enhancement of drug permeability was 4.1-fold for transdermal delivery of granisetron hydrochloridein comparison with the control group (20% of tween 85 and 20% of ethanol micelle solution containing 2.5% of granisetron hydrochloride without IPM), and cumulative permeation amount was the highest (891.8+/-2.86 microg/cm(2)) with the shortest lag time (0.11+/-0.02 h) and was stable for at least 12 months. Therefore, the nanoemulsion system developed in this study offers a promising vehicle for the transdermal delivery system of granisetron hydrochloride, which may be as effective as oral or intravenous dosage forms and avoid some difficulties associated with these dosage forms.
本研究的目的是开发并评估用于盐酸格拉司琼经皮给药的纳米乳剂系统。构建了伪三元相图，以确定由肉豆蔻酸异丙酯（IPM）作为油相、吐温85作为表面活性剂、乙醇作为助表面活性剂、水作为水相组成的纳米乳剂各组分的浓度范围。体外研究了油相IPM含量和透皮促进剂N-甲基吡咯烷酮（NMP）对盐酸格拉司琼纳米乳剂大鼠皮肤渗透的影响。结果表明，纳米乳剂的平均粒径在50.4±1.5至82.4±0.9nm之间，粒径分布均匀。所得到的最佳配方由2.5%盐酸格拉司琼、4% IPM、40%吐温85/乙醇（1:1）和10% NMP组成，结果显示皮肤渗透速率最高（85.39±2.90μg/cm²/h），与对照组（含2.5%盐酸格拉司琼的20%吐温85和20%乙醇胶束溶液，不含IPM）相比，盐酸格拉司琼经皮给药的药物渗透增强了4.1倍，累积渗透量最高（891.8±2.86μg/cm²），滞后时间最短（0.11±0.02h），且至少12个月稳定。因此，本研究开发的纳米乳剂系统为盐酸格拉司琼经皮给药系统提供了一种有前景的载体，其可能与口服或静脉剂型一样有效，并避免了与这些剂型相关的一些困难。
