Simulating the hydrodynamic conditions of the human ascending colon: a digital twin of the dynamic colon model

Michael Schütt, Connor O’Farrell, Konstantinos Stamatopoulos, Caroline L. Hoad, Luca Marciani, Sarah Sulaiman, Mark J. H. Simmons, Hannah K. Batchelor, Alessio Alexiadis

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Abstract

The performance of solid oral dosage forms targeting the colon is typically evaluated using standardised pharmacopeial dissolution apparatuses. However, these fail to replicate colonic hydrodynamics. This study develops a digital twin of the Dynamic Colon Model; a physiologically representative in vitro model of the human proximal colon. Magnetic resonance imaging of the Dynamic Colon Model verified that the digital twin robustly replicated flow patterns under different physiological conditions (media viscosity, volume, and peristaltic wave speed). During local contractile activity, antegrade flows of 0.06−0.78 cm s−1 and backflows of −2.16−−0.21 cm s−1 were measured. Mean wall shear rates were strongly time and viscosity dependent although peaks were measured between 3.05−10.12 s−1 and 5.11−20.34 s−1 in the Dynamic Colon Model and its digital twin respectively, comparable to previous estimates of the USPII with paddle speeds of 25 and 50 rpm. It is recommended that viscosity and shear rates are considered when designing future dissolution test methodologies for colon-targeted formulations. In the USPII, paddle speeds >50 rpm may not recreate physiologically relevant shear rates. These findings demonstrate how the combination of biorelevant in vitro and in silico models can provide new insights for dissolution testing beyond established pharmacopeial methods.
Original languageEnglish
Article number184
Number of pages23
JournalPharmaceutics
Volume14
Issue number1
Early online date13 Jan 2022
DOIs
Publication statusPublished - 13 Jan 2022

Keywords

  • Dynamic Colon Model (DCM)
  • digital twin
  • discrete multiphysics
  • Smoothed Particle Hydrodynamics (SPH)
  • large intestine
  • colon
  • shear rate
  • dissolution apparatus
  • Magnetic Resonance Imaging (MRI)
  • colon targeted drug delivery

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