Luminal fluid motion inside an in vitro dissolution model of the human ascending colon assessed using magnetic resonance imaging

Connor O’farrell, Caroline L. Hoad, Konstantinos Stamatopoulos, Luca Marciani, Sarah Sulaiman, Mark J. H. Simmons, Hannah K. Batchelor

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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.
Original languageEnglish
Article number1545
Number of pages26
JournalPharmaceutics
Volume13
Issue number10
DOIs
Publication statusPublished - 23 Sept 2021

Bibliographical note

Funding Information:
Funding: This research was funded by the EPSRC Centre for Doctoral Training in Formulation Engineering (EP/L015153/1), AstraZeneca AB R&D, Gothenburg. Additionally, the School of Medicine at the University of Nottingham contributed to the MRI scanning costs as part of SS’s postgraduate research study programme.

Funding Information:
Acknowledgments: The authors would like to thank the EPSRC Centre for Doctoral Training in Formulation Engineering, AstraZeneca AB R&D, Gothenburg and the School of Medicine at the University of Nottingham for sponsoring this research and contributing to the scanning costs.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • dynamic colon model (DCM)
  • large intestine
  • colon
  • colon-specific drug formulations
  • colonic flow
  • phase contrast cine-MRI
  • MR tagging
  • colonic mixing

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