Hydrodynamic Effects on Drug Dissolution and Deaggregation in the Small Intestine-A Study with Felodipine as a Model Drug.
Hydrodynamic Effects on Drug Dissolution and Deaggregation in the Small Intestine-A Study with Felodipine as a Model Drug.
复制标题
水动力对小肠药物溶解和解聚的影响——以非洛地平为模型药物的研究。
DOI：
--
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
B. Abrahamsson
中科院分区：
文献类型：
--
作者：
L. Lindfors;M. Jonsson;Emelie Weibull;J. Brasseur;B. Abrahamsson
本研究的目的是了解和预测在小肠中的流体动力学效应对初级和聚集的药物颗粒的溶解的影响。在与进食小肠相对应的流体动力学试验条件下，在Couette池中进行了含有低溶解度药物非洛地平的混悬液的溶出试验。还在USP II装置中以25和200 rpm的两种桨速和低于临界胶束浓度的不同表面活性剂浓度进行溶出。实验的溶出速率与理论计算进行了比较。体外试验中不同水平的剪切应力不影响初级或聚集颗粒的溶出，并且实验溶出速率与计算值非常一致。加入表面活性剂后，药物聚集体颗粒的溶出速率因解聚集而增加，但流体动力学的影响仍不明显。总之，流体动力学不影响该模型药物在小肠中的微粉化药物颗粒的溶解和解聚集。表面张力对解聚集和随后的溶解具有强烈的影响。因此，在体内相关表面张力水平下添加表面活性剂对于体内预测性体外溶出试验至关重要。
The aim of this study was to understand and predict the influence of hydrodynamic effects in the small intestine on dissolution of primary and aggregated drug particles. Dissolution tests of suspensions with a low-solubility drug, felodipine, were performed in a Couette cell under hydrodynamic test conditions corresponding to the fed small intestine. Dissolution was also performed in the USP II apparatus at two paddle speeds of 25 and 200 rpm and at different surfactant concentrations below critical micelle concentration. The experimental dissolution rates were compared with theoretical calculations. The different levels of shear stress in the in vitro tests did not influence the dissolution of primary or aggregated particles and experimental dissolution rates corresponded very well to calculations. The dissolution rate for the aggregated drug particles increased after addition of surfactant because of deaggregation, but there were still no effect of hydrodynamics. In conclusion, hydrodynamics do not influence dissolution and deaggregation of micronized drug particles in the small intestine of this model drug. Surface tension has a strong effect on the deaggregation and subsequent dissolution. Addition of surfactants at in vivo relevant surface tension levels is thus critical for in vivo predictive in vitro dissolution testing.
USP 溶出度仪 II 中的颗粒扩散层厚度：颗粒尺寸和桨速度的组合函数。
影响因子：
3.8
作者：
Sheng,JenniferJ;Sirois,PaulJ;Dressman,JenniferB;Amidon,GordonL
通讯作者：
Amidon,GordonL