Mathematical modelling of the fluid dynamics involved in colonic mixing with applications to drug delivery

Davies, Allison Bridget Mary (2015). Mathematical modelling of the fluid dynamics involved in colonic mixing with applications to drug delivery. University of Birmingham. Ph.D.

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Abstract

Within the pharmaceutical industry there is current interest in the proximal colon as a site for drug delivery. Segmental contractions of the smooth colonic muscle are the most prevalent type; these promote the mixing of material within the lumen, which in turn aids absorption. Few physical or theoretical models have been developed to assist with the understanding of dosage form behaviour within the colon.

We model the colon as a cylindrical pipe, whose boundary represents the circular muscle layer. Assuming the boundary is axisymmetric and that the contractions may be modelled by a standing wave of small amplitude, we employ a perturbation expansion to describe the behaviour of both one and two layer fluid flow using various rheological models.

Utilising the results and Lagrangian particle tracking we create a model of drug delivery which analyses the proportion, by volume, of a drug reaching the colonic epithelium, discovering that the segmental contractions of the colon lead to effective mixing of the fluid. We investigate the results of varying the fluid rheology and contractile properties, finding that the amplitude of contraction has the largest effect on the proportion of particles absorbed. The results prove themselves robust to variation in contractile frequency, fluid viscosity and ratio between radius and wavelength, which is promising in terms of consistent drug delivery across a range of physiological states.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):