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
Affiliations
Michael Schütt
School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Connor O’Farrell
School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Konstantinos Stamatopoulos
School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Caroline L. Hoad
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 2UK, UK
Luca Marciani
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 2UK, UK
Sarah Sulaiman
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 2UK, UK
Mark J. H. Simmons
School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Hannah K. Batchelor
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK
Alessio Alexiadis
School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
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.
