Schütt M, Stamatopoulos K, Simmons M J H, Batchelor H K, Alexiadis A
School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.
School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.
Comput Biol Med. 2020 Jun;121:103819. doi: 10.1016/j.compbiomed.2020.103819. Epub 2020 May 18.
The proximal part of the colon offers opportunities to prolong the absorption window following oral administration of a drug. In this work, we used computer simulations to understand how the hydrodynamics in the proximal colon might affect the release from dosage forms designed to target the colon. For this purpose, we developed and compared three different models: a completely-filled colon, a partially-filled colon and a partially-filled colon with a gaseous phase present (gas-liquid model). The highest velocities of the liquid were found in the completely-filled model, which also shows the best mixing profile, defined by the distribution of tracking particles over time. No significant differences with regard to the mixing and velocity profiles were found between the partially-filled model and the gas-liquid model. The fastest transit time of an undissolved tablet was found in the completely-filled model. The velocities of the liquid in the gas-liquid model are slightly higher along the colon than in the partially-filled model. The filling level has an impact on the exsisting shear forces and shear rates, which are decisive factors in the development of new drugs and formulations.
结肠近端为口服给药后延长吸收窗口提供了机会。在这项研究中，我们使用计算机模拟来了解近端结肠中的流体动力学如何影响旨在靶向结肠的剂型的释放。为此，我们开发并比较了三种不同的模型：完全充满的结肠模型、部分充满的结肠模型和存在气相的部分充满的结肠模型（气液模型）。在完全充满的模型中发现液体的速度最高，该模型还显示出最佳的混合分布，这由追踪颗粒随时间的分布定义。在部分充满的模型和气液模型之间，在混合和速度分布方面未发现显著差异。在完全充满的模型中发现未溶解片剂的最快通过时间。气液模型中液体沿结肠的速度比部分充满的模型略高。填充水平对现有的剪切力和剪切速率有影响，而剪切力和剪切速率是新药和制剂开发中的决定性因素。
