Li Ying, Zhang Yun, Zhu Chun-Yan
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
Chin J Nat Med. 2017 Feb;15(2):142-151. doi: 10.1016/S1875-5364(17)30029-8.
The present study was designed to prepare and compare bio-adhesive pellets of panax notoginseng saponins (PNS) with hydroxy propyl methyl cellulose (HPMC), chitosan, and chitosan : carbomer, explore the influence of different bio-adhesive materials on pharmacokinetics behaviors of PNSbio-adhesive pellets, and evaluate the correlation between in vivo absorption and in vitro release (IVIVC). In order to predict the in vivo concentration-time profile by the in vitro release data of bio-adhesive pellets, the release experiment was performed using the rotating basket method in pH 6.8 phosphate buffer. The PNS concentrations in rat plasma were analyzed by HPLC-MS-MS method and the relative bioavailability and other pharmacokinetic parameters were estimated using Kinetica4.4 pharmacokinetic software. Numerical deconvolution method was used to evaluate IVIVC. Our results indicated that, compared with ordinary pellets, PNS bio-adhesive pellets showed increased oral bioavailability by 1.45 to 3.20 times, increased C, and extended MRT. What's more, the release behavior of drug in HPMC pellets was shown to follow a Fickian diffusion mechanism, a synergetic function of diffusion and skeleton corrosion. The in vitro release and the in vivo biological activity had a good correlation, demonstrating that the PNS bio-adhesive pellets had a better sustained release. Numerical deconvolution technique showed the advantage in evaluation of IVIVC for self-designed bio-adhesive pellets with HPMC. In conclusion, the in vitro release data of bio-adhesive pellets with HPMC can predict its concentration-time profile in vivo.
本研究旨在制备并比较三七总皂苷（PNS）与羟丙基甲基纤维素（HPMC）、壳聚糖以及壳聚糖：卡波姆制成的生物黏附微丸，探讨不同生物黏附材料对PNS生物黏附微丸药代动力学行为的影响，并评估体内吸收与体外释放之间的相关性（体内外相关性，IVIVC）。为了通过生物黏附微丸的体外释放数据预测体内浓度-时间曲线，采用转篮法在pH 6.8的磷酸盐缓冲液中进行释放实验。采用HPLC-MS-MS法分析大鼠血浆中的PNS浓度，并使用Kinetica4.4药代动力学软件估算相对生物利用度和其他药代动力学参数。采用数值反卷积法评估IVIVC。我们的结果表明，与普通微丸相比，PNS生物黏附微丸的口服生物利用度提高了1.45至3.20倍，Cmax增加，平均滞留时间（MRT）延长。此外，HPMC微丸中药物的释放行为显示遵循菲克扩散机制，是扩散和骨架溶蚀的协同作用。体外释放与体内生物活性具有良好的相关性，表明PNS生物黏附微丸具有更好的缓释效果。数值反卷积技术在评估自制HPMC生物黏附微丸的IVIVC方面显示出优势。总之，含HPMC的生物黏附微丸的体外释放数据可以预测其体内浓度-时间曲线。
