Dynamic Colon Model (DCM): A Cine-MRI Informed Biorelevant In Vitro Model of the Human Proximal Large Intestine Characterized by Positron Imaging Techniques

Department of Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, UK

Department of Radiology, University Hospitals Birmingham NHS Foundation Trust, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, UK

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Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK

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Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham NG7 2QX, UK

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Institute of Clinical Sciences, College of Medical and Dental Sciences, Medical School Building, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK

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Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK

Author to whom correspondence should be addressed.

Pharmaceutics 2020, 12(7), 659; https://doi.org/10.3390/pharmaceutics12070659

Received: 8 June 2020 / Revised: 9 July 2020 / Accepted: 10 July 2020 / Published: 13 July 2020

(This article belongs to the Special Issue In Vivo Predictive Dissolution (iPD): Experimental and Mathematical Approaches and Regulatory Applications)

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Abstract

This work used in vivo MRI images of human colon wall motion to inform a biorelevant Dynamic Colon Model (DCM) to understand the interplay of wall motion, volume, viscosity, fluid, and particle motion within the colon lumen. Hydrodynamics and particle motion within the DCM were characterized using Positron Emission Tomography (PET) and Positron Emission Particle Tracking (PEPT), respectively. In vitro PET images showed that fluid of higher viscosity follows the wall motion with poor mixing, whereas good mixing was observed for a low viscosity fluid. PEPT data showed particle displacements comparable to the in vivo data. Increasing fluid viscosity favors the net forward propulsion of the tracked particles. The use of a floating particle demonstrated shorter residence times and greater velocities on the liquid surface, suggesting a surface wave that was moving faster than the bulk liquid. The DCM can provide an understanding of flow motion and behavior of particles with different buoyancy, which in turn may improve the design of drug formulations, whereby fragments of the dosage form and/or drug particles are suspended in the proximal colon. View Full-Text

Keywords: dynamic colon model (DCM); colon-specific drug formulations; magnetic resonance imaging (MRI); positron emission tomography (PET); in vitro models; dissolution; colon motility; cine-MRI

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MDPI and ACS Style

Stamatopoulos, K.; Karandikar, S.; Goldstein, M.; O’Farrell, C.; Marciani, L.; Sulaiman, S.; Hoad, C.L.; Simmons, M.J.H.; Batchelor, H.K. Dynamic Colon Model (DCM): A Cine-MRI Informed Biorelevant In Vitro Model of the Human Proximal Large Intestine Characterized by Positron Imaging Techniques. Pharmaceutics 2020, 12, 659. https://doi.org/10.3390/pharmaceutics12070659

AMA Style

Stamatopoulos K, Karandikar S, Goldstein M, O’Farrell C, Marciani L, Sulaiman S, Hoad CL, Simmons MJH, Batchelor HK. Dynamic Colon Model (DCM): A Cine-MRI Informed Biorelevant In Vitro Model of the Human Proximal Large Intestine Characterized by Positron Imaging Techniques. Pharmaceutics. 2020; 12(7):659. https://doi.org/10.3390/pharmaceutics12070659

Chicago/Turabian Style

Stamatopoulos, Konstantinos, Sharad Karandikar, Mark Goldstein, Connor O’Farrell, Luca Marciani, Sarah Sulaiman, Caroline L. Hoad, Mark J.H. Simmons, and Hannah K. Batchelor. 2020. "Dynamic Colon Model (DCM): A Cine-MRI Informed Biorelevant In Vitro Model of the Human Proximal Large Intestine Characterized by Positron Imaging Techniques" Pharmaceutics 12, no. 7: 659. https://doi.org/10.3390/pharmaceutics12070659

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Dynamic Colon Model (DCM): A Cine-MRI Informed Biorelevant In Vitro Model of the Human Proximal Large Intestine Characterized by Positron Imaging Techniques

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