Luminal Fluid Motion Inside an In Vitro Dissolution Model of the Human Ascending Colon Assessed Using Magnetic Resonance Imaging.
Luminal Fluid Motion Inside an In Vitro Dissolution Model of the Human Ascending Colon Assessed Using Magnetic Resonance Imaging.
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DOI：
10.3390/pharmaceutics13101545
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发表时间：
2021-09-23
期刊：
影响因子：
5.4
通讯作者：
Batchelor HK
中科院分区：
文献类型：
--
作者：
O'Farrell C;Hoad CL;Stamatopoulos K;Marciani L;Sulaiman S;Simmons MJH;Batchelor HK
人类结肠内腔流的知识仍然难以捉摸，尽管它对设计新的结肠靶向药物输送系统和结肠内溶解力学的生理相关的计算机模型很重要。本研究使用磁共振成像（MRI）技术来观察、测量和区分具有解剖学代表性的人类升结肠体外溶解模型中的不同运动模式：动态结肠模型（DCM）。DCM的分段结构和蠕动式收缩活动产生的流动曲线与药典溶解仪不同。MRI使用一种新的标记方法，通过混合相关运动的程度对不同的运动模式进行分类。不同的培养基粘度也可以被区分，这对于理解结肠病理生理、结肠靶向剂型可能受到的条件和治疗的有效性是重要的。标记的MRI数据显示，DCM有效地模拟了人升结肠的壁运动、腔内流动模式和内容物的速度。准确再现体内流体动力学是结肠生物相关力学模型的基本能力，使其适合体外数据生成，用于体外体内评估（IVIVE）或体外体内相关（IVIVC）。与传统的药典方法相比，这项工作说明了DCM如何为结肠壁的运动如何控制腔流体动力学、驱动剂型的侵蚀和随后的药物释放提供了新的见解。
Knowledge of luminal flow inside the human colon remains elusive, despite its importance for the design of new colon-targeted drug delivery systems and physiologically relevant in silico models of dissolution mechanics within the colon. This study uses magnetic resonance imaging (MRI) techniques to visualise, measure and differentiate between different motility patterns within an anatomically representative in vitro dissolution model of the human ascending colon: the dynamic colon model (DCM). The segmented architecture and peristalsis-like contractile activity of the DCM generated flow profiles that were distinct from compendial dissolution apparatuses. MRI enabled different motility patterns to be classified by the degree of mixing-related motion using a new tagging method. Different media viscosities could also be differentiated, which is important for an understanding of colonic pathophysiology, the conditions that a colon-targeted dosage form may be subjected to and the effectiveness of treatments. The tagged MRI data showed that the DCM effectively mimicked wall motion, luminal flow patterns and the velocities of the contents of the human ascending colon. Accurate reproduction of in vivo hydrodynamics is an essential capability for a biorelevant mechanical model of the colon to make it suitable for in vitro data generation for in vitro in vivo evaluation (IVIVE) or in vitro in vivo correlation (IVIVC). This work illustrates how the DCM provides new insight into how motion of the colonic walls may control luminal hydrodynamics, driving erosion of a dosage form and subsequent drug release, compared to traditional pharmacopeial methods.
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