Simulating the Hydrodynamic Conditions of the Human Ascending Colon: A Digital Twin of the Dynamic Colon Model.
Simulating the Hydrodynamic Conditions of the Human Ascending Colon: A Digital Twin of the Dynamic Colon Model.
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DOI：
10.3390/pharmaceutics14010184
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发表时间：
2022-01-13
期刊：
影响因子：
5.4
通讯作者：
Alexiadis A
中科院分区：
文献类型：
--
作者：
Schütt M;O'Farrell C;Stamatopoulos K;Hoad CL;Marciani L;Sulaiman S;Simmons MJH;Batchelor HK;Alexiadis A
针对结肠的固体口服剂型的性能通常使用标准化的药典溶出仪进行评估。然而，这些都不能复制结肠的流体动力学。这项研究开发了动态结肠模型的数字双胞胎；动态结肠模型是人体近端结肠的一个具有生理学代表性的体外模型。动态结肠模型的磁共振成像证实，数字孪生兄弟在不同的生理条件(介质粘度、体积和蠕动波速)下稳健地复制了流动模式。在局部收缩活动过程中，测量到S−1前向血流0.06~0.78 cm，−2.16~−0.21 cm S−1返流。平均室壁切变率与时间和粘度有很强的相关性，尽管在动态结肠模型和它的数字孪生模型中分别在3·05-10·12 S−1和5·11-20·34 S−1之间测量到峰值，与先前估计的桨速度为25和50 rpm的USPII相当。建议在设计结肠靶向制剂的未来溶出度测试方法时考虑粘度和剪切率。在USPII中，划桨速度&50rpm可能无法重建生理上相关的切变率。这些发现表明，生物分离剂在体外和硅胶模型中的结合如何在现有的药典方法之外为溶出度测试提供新的见解。
The performance of solid oral dosage forms targeting the colon is typically evaluated using standardised pharmacopeial dissolution apparatuses. However, these fail to replicate colonic hydrodynamics. This study develops a digital twin of the Dynamic Colon Model; a physiologically representative in vitro model of the human proximal colon. Magnetic resonance imaging of the Dynamic Colon Model verified that the digital twin robustly replicated flow patterns under different physiological conditions (media viscosity, volume, and peristaltic wave speed). During local contractile activity, antegrade flows of 0.06–0.78 cm s−1 and backflows of −2.16–−0.21 cm s−1 were measured. Mean wall shear rates were strongly time and viscosity dependent although peaks were measured between 3.05–10.12 s−1 and 5.11–20.34 s−1 in the Dynamic Colon Model and its digital twin respectively, comparable to previous estimates of the USPII with paddle speeds of 25 and 50 rpm. It is recommended that viscosity and shear rates are considered when designing future dissolution test methodologies for colon-targeted formulations. In the USPII, paddle speeds >50 rpm may not recreate physiologically relevant shear rates. These findings demonstrate how the combination of biorelevant in vitro and in silico models can provide new insights for dissolution testing beyond established pharmacopeial methods.
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影响因子：
3.8
作者：
Hopgood, Matthew;Reynolds, Gavin;Barker, Richard
通讯作者：
Barker, Richard
影响因子：
5.4
作者：
O'Farrell C;Hoad CL;Stamatopoulos K;Marciani L;Sulaiman S;Simmons MJH;Batchelor HK
通讯作者：
Batchelor HK
影响因子：
2.5
作者：
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通讯作者：
Alexiadis, Alessio
影响因子：
4.4
作者：
O'Brien, Kieran R.;Cowan, Brett R.;Young, Alistair A.
通讯作者：
Young, Alistair A.
影响因子：
3.5
作者：
Dinning PG;Wiklendt L;Maslen L;Gibbins I;Patton V;Arkwright JW;Lubowski DZ;O'Grady G;Bampton PA;Brookes SJ;Costa M
通讯作者：
Costa M