Development of a biorelevant dynamic model of human proximal colon: a tool for designing colon – specific drug delivery systems

Stamatopoulos, Konstantinos (2017). Development of a biorelevant dynamic model of human proximal colon: a tool for designing colon – specific drug delivery systems. University of Birmingham. Ph.D.

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Abstract

A novel Dynamic Colon Model (DCM) that represents the anatomy and physiology of the human proximal colon was developed. Analysis of the hydrodynamics was performed using Positron Emission Particle Tracking (PEPT) system and Positron Emission Tomography (PET). The pressures generated by the wall motion of the DCM tube compared with the available published in vivo data. The hydrodynamics in USP 2 dissolution apparatus were also assessed using Particle Image Velocimetry (PIV) and Planar Induced Fluorescence (PLIF). Areal distribution and individual striation methods showed high mixedness level close to tip.
PEPT experiments were performed using particles of different buoyancy. Use of different particles gave different results in terms of velocities and residence times within the DCM tube.
PET images showed that antegrade propagating waves of amplitude lower than the minimum threshold used in vivo studies were associated with flow episodes. In addition, flow episodes can occur which are not related to the wall motion.
Dissolution profiles of theophylline, a high water soluble drug, released from a hydrophilic matrix obtained at viscous shear thinning media, mimicking the dewatering process in the human colon.
The novel DCM provides a realistic colonic environment, enabling biorelevant in vitro assessment of the in vivo performance of dosage forms.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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