Abstract
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.
Highlights
This work demonstrates that a noninvasive Magnetic resonance (MR) tagging method developed to assess human colonic motility and distinguish between colonic disease states, can differentiate between motility patterns and media viscosities in a biorelevant in vitro model of the human ascending colon
It was demonstrated that the dynamic colon model (DCM) can induce flow that replicates the flow patterns observed in vivo, of a similar velocity magnitude
To reproduce the hydrodynamics of the human ascending colon is an essential capability for a biorelevant mechanical dissolution apparatus to be suitable for the development of methods facilitating in vivo evaluation (IVIVE) or in vivo correlation (IVIVC)
Summary
Knowledge of luminal flow inside the human colon remains elusive, as this anatomical region is difficult to access and current techniques are generally invasive. Improved knowledge would enable a greater understanding of colonic physiology and pathology, enhancing the capability to design new or improved colon-targeted drug delivery systems. Targeted drug delivery to the ascending colon (AC) offers a promising opportunity for local administration of effective therapeutics for a range of conditions, such as inflammatory. Pharmaceutics 2021, 13, 1545 bowel disease, colon cancer and irritable bowel syndrome, all of which have enormous and increasing prevalence across the globe [1,2,3]. In the case of colorectal cancer (CRC), it is the fourth most commonly diagnosed and third most deadly cancer worldwide [1]
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