普罗布考纳米混悬液的制备及其家兔体内药动学研究  

Preparation and in Vivo Evaluation of Probucol Nanosuspensions

作　　者：吕守磊[1] 靳文仙[2,3] 王成港[2,3] 王春龙[2,3] 

机构地区：[1]河南大学药学院,河南开封475001 [2]天津药物研究院,天津300193 [3]天津泰普药品科技发展有限公司,天津300193

出　　处：《中国药学杂志》2010年第21期1634-1638,共5页Chinese Pharmaceutical Journal

摘　　要：目的以普罗布考为模型,研究纳米混悬液提高难溶性药物生物利用度的可行性。方法采用高压乳匀法制备纳米混悬液;采用Zetasizer nano ZS90测定其粒径和ζ电位;采用Tecnai G220 S-TWIN观察其外观形态;采用高效液相色谱法,以Iner-sil C8柱为色谱柱,乙腈-水(85∶15)为流动相测定其含量;以日本大耳兔为实验对象,测定其血药浓度随时间的变化曲线。结果自制纳米混悬液中药物形态为类球形,载药量为101.04 mg.mL-1,粒径为364.9 nm,ζ电位为-24.1 mV;经影响因素和稳定性实验可知,纳米混悬液稳定性良好;血药浓度峰值较片剂提高了290%。结论通过纳米混悬液技术,显著提高了普罗布考的生物利用度,该方法为解决难溶性药物的生物利用度低的问题提供了一个参考。OBJECTIVE To study the nanosuspensions which can improve bioavailability of insoluble drugs,with probucol as a model drug.METHODS The content of probucol nanosuspensions was measured by the high-pressure homogenization method.Particle size and Zeta potential of probucol nanosuspensions was determined by Zetasizer nano ZS90.Appearance was viewed by Tecnai G220 S-TWIN.The separation was performed with a Intersil C8 column（4.6 mm×250 mm,5 μm）,and the mobile phase was acetonitrile-water（85∶15） at a flow rate of 1.0 mL·min-1 and probucol is detected at 242 nm,35 ℃ temperature.Plasma concentration vs time curve is measured,with Japanese White Rabbit as experimental object.RESULTS Probucol had a good linear re1ation in the range of 1-25 mg·mL-1（r=1.000 0,n=6）,the average recovery was 100.45%.Probucol nanosuspensions was spherical when viewed under the electron microscope.The drugs loading of self-made nanosuspension was 101.04 mg·mL-1,the particle size was 364.9 nm,Zeta potential was-24.1 mV.Compared to table,the peak plasma concentration increases 290%.Stability studies proved probucol nanosuspensions was stable after two months storage except at 60 ℃.CONCLUSION Through the nanosuspension technology significantly improves the bioavailability of probucol.This paper introduce the methods which to solve the problem on how to improve the solubility of insoluble drugs.

关 键 词：普罗布考 纳米混悬液 高压乳匀法 药动学 

分 类 号：R944[医药卫生—药剂学]