A Dynamic Colon Model (DCM) of human proximal colon:

a tool for designing targeted drug delivery systems

bioinspiration

Human colon DCM

1Konstantinos Stamatopoulos

2Dr Hannah K. Batchelor

1Prof. Mark J. H. Simmons

1School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, UK 2Pharmacy and Therapeutics Section, Medical School Building, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom

COLLEGE OF

MEDICAL AND

DENTAL SCIENCES

Development of a biorelevant model of the colon that mimics the

pressure, motility and fluid flow within the human proximal colon.

Use of clinical data (e.g. MRI images) to design and fabricate

the biorelevant in vitro model

Use of manometry to monitor and reproduce the physical

pressure amplitudes inside the in vitro model

Use the proposed in vitro model to evaluate the performance of

modified release dosage forms

Back ground of the Innovation

Sketch Reconstructed 2D model MRI images

a

b

z

x

y

x

Semilunar folds

Relaxation stage

Semilunar folds

Neutral position

Clinical observations show the architecture of the proximal colon

Dimensions of the DCM are based on MRI images and the average values obtained from literature in

terms of length, diameter of the cecum – ascending region and the width of each pocket

3D model

Back ground of the Innovation

Solid-state catheter

DCM

segment

Reservoirs filled with

different viscous media

Pressure profile of different viscosities and membrane occlusion rates: 1) 4.3 mm s-1; 2) 8.5 mm s-1; 3) 10.6 mm s-1

73% occlusion Initial position

Monitoring pressure events inside the cavity of a single segment

Establishing relationship between pressure events and membrane motion for different viscous media

1 2 3

The DCM

Realistic simulation of human colon motility and pressure forces

Reproducing the in vivo manometry data

Unlimited number of different motility patterns by changing occlusion degree and rate of each segment and the

wave speed; mimicking the change on the motility index of the colon due to different bowel diseases

Choosing between fixed volume of the fluids or adjustment can be done by controlling the flow rate through the

ileum terminal using peristaltic pump

Monitoring pH

Controlling temperature using infrared technology

Monitoring released drug distribution within the DCM tube (max 10 sampling point)

Ileum terminal

Cecum

Haustrum

Rigid body (‘hepatic flexure’)

Membrane

Tube for sampling

Monitoring fluid motion

Positron Emission Particle Tracking system (PEPT)

Neutrally buoyant particle

DCM tube

Fluid level (half filled)

Data density of the axial displacements of floating and neutrally buoyance particle in cross section of the DCM tube in different viscous media.

- Case study: Dissolution profile of extended release dosage form

Time (h)

0 2 4 6 8 10

Th

eo

ph

yllin

e r

ele

ased

(%

)

0

20

40

60

80

100

S1

S2

S3

0.50% NaCMC (w/w)

Time (h)

0 2 4 6 8 10

Th

eo

ph

yllin

e r

ele

ase

d (

%)

0

20

40

60

80

100

Dissolution curves of theophylline obtained from three different sampling points along the length of the DCM tube (beginning,

S1; middle, S2; at the end, S3). The dissolution experiments were performed in (a) 0.25% and (b) 0.50% NaCMC(700000)

(w/w) solutions.

a

b

a b S1 S2 S3

1st case

Thermocouple

b’

x

z

S1 S3

y

z

b’

2nd case

- Fragments of the tablet - Accumulation area of the drug

a’

a’

A B

- Distribution of the drug within the DCM tube (two cases)

(A) Images of the cross section of the DCM

tube and (B) schematic illustration of the in

vitro model along the x axis, showing the

position of the partially disintegrated tablet

in two separated runs of the dissolution

experiments.