A digital twin of the human colon for the design and optimisation of colon-targeted drug delivery systems

Schütt, Michael ORCID: 0000-0003-4857-7768 (2023). A digital twin of the human colon for the design and optimisation of colon-targeted drug delivery systems. University of Birmingham. Ph.D.

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Abstract

The performance of a solid dosage form targeting the colon is commonly assessed using standardised pharmacopeial dissolution apparatuses like the USP II or the miniaturised replica, the mini-USP II. However, these dissolution apparatuses fail to replicate the hydrodynamics and shear stresses in the colonic environment. These parameters are crucial for the tablet’s drug release process and the distribution of the dissolved active pharmaceutical ingredient along the colon. The ascending part of the colon is the most favourable side for colonic drug delivery as it offers the most suitable environmental conditions for drug dissolution. In this thesis, a mesh-less particle method called Discrete Multiphysics is used where particles represent both the fluid and solid phases. This framework combines particle methods such as Smoothed Particle Hydrodynamics for fluid mechanics and Lattice Spring Model for solid mechanics. The modelling technique is used to build three different types of models: (i) a model of the proximal colon, which can replicate in vivo motility patterns, (ii) a model of a tablet that dissolves/disintegrates in the colonic environment; and (iii) a model of the mini-USP II dissolution apparatus to compare the performance of a solid dosage form in a standardised dissolution apparatus and a biorelevant colon model. These Discrete Multiphysics models have made it possible to analyse the hydrodynamics in the colon, the shear rates acting on a tablet, and the performance of different motility patterns in the colon concerning drug distribution and therefore offers the first step to a spatiotemporal dissolution profile of the colon.

Type of Work:	Thesis (Doctorates > Ph.D.)
Award Type:	Doctorates > Ph.D.
Supervisor(s):	Supervisor(s) Email ORCID Alexiadis, Alessio UNSPECIFIED orcid.org/0000-0001-9240-3517 Simmons, Mark J. H. UNSPECIFIED orcid.org/0000-0002-0655-3744 Stamatopoulos, Konstantinos UNSPECIFIED orcid.org/0000-0002-7524-2800
Licence:	All rights reserved
College/Faculty:	Colleges (2008 onwards) > College of Engineering & Physical Sciences
School or Department:	School of Chemical Engineering
Funders:	Engineering and Physical Sciences Research Council
Subjects:	Q Science > QM Human anatomy R Medicine > R Medicine (General) R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica
URI:	http://etheses.bham.ac.uk/id/eprint/13249

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