全东琴, 徐贵霞. 全反式维甲酸自乳化给药系统的体内外评价J. 药学学报, 2005, 40(1): 76-79.
引用本文: 全东琴, 徐贵霞. 全反式维甲酸自乳化给药系统的体内外评价J. 药学学报, 2005, 40(1): 76-79.
QUAN Dong-qin, XU Gui-xia. Assesement of tretinoin with a self-emulsifying formulation in vitro and in vivoJ. Acta Pharmaceutica Sinica, 2005, 40(1): 76-79.
Citation: QUAN Dong-qin, XU Gui-xia. Assesement of tretinoin with a self-emulsifying formulation in vitro and in vivoJ. Acta Pharmaceutica Sinica, 2005, 40(1): 76-79.

全反式维甲酸自乳化给药系统的体内外评价

Assesement of tretinoin with a self-emulsifying formulation in vitro and in vivo

  • 摘要: 目的研究全反式维甲酸(RA)自乳化释药系统的自乳化能力及在比格犬体内的药代动力学。方法通过测定不同时间粒子的散射光强度来评价自乳化速度,光学显微镜下观察乳化后形成乳剂粒径的大小及分布情况;采用HPLC法测定比格犬血浆药物浓度,与市售胶囊比较,考察RA自乳化制剂体外溶出行为及体内药代动力学。结果体系在10 min内已基本乳化完全,通过光学显微镜观察,乳化后乳剂粒子大多数在3 μm以下。与市售胶囊剂相比:以水为溶出介质,维甲酸自乳化制剂15 min可以溶出80%以上,而市售胶囊溶出不到5%。比格犬体内药代动力学研究结果表明:与市售胶囊剂相比,自乳化制剂达峰时间提前,Tmax=1.25 h,而市售胶囊 Tmax=2 h;AUC0-∞提高了67%。结论自乳化制剂可以显著提高RA的体外溶出及体内吸收。

     

    Abstract: AimTo evaluate the self-emulsifying ability and dissolution behavior of tretinoin in vitro and the pharmacokinetic behavior in beagle dogs. MethodsThe self-emulsifying rate was evaluated by determining the intensity of scattered light at different time and the particle size of resultant emulsions after self-emulsifying were observed by optical microscope. The plasma concentrations were determined by HPLC and dissolution and pharmacokinetic behavior of self-emulsifying formulations were evaluated by comparison with commercial capsules. ResultsThe area under the curve (AUC) was significantly higher in the tretinoin self-emulsifying formulation group (3 048.0 mg·h·L-1) than that in the commercial capsule group (1 826.0 mg·h·L-1). Also, Tmax was smaller in the self-emulsifying formulation group (1.25 h) compared with market products (2 h) and the dissolved amount from self-emulsifying formulations in water at 15 min was much higher (more than 80%) than that of the market products (less than 5%). ConclusionThe self-emulsifying drug delivery systems can increase drug dissolution in vitro and absorption in vivo significantly.

     

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