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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 modelMRI 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% occlusionInitial 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
Theophyllinereleased(%)
0
20
40
60
80
100
S1
S2
S3
0.50% NaCMC (w/w)
Time (h)
0 2 4 6 8 10
Theophyllinereleased(%)
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 bS1 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.

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Dynamic Colon Model

  • 1. 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
  • 2.  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
  • 3. Back ground of the Innovation Sketch Reconstructed 2D modelMRI 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
  • 4. 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% occlusionInitial 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
  • 5. 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
  • 6. 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.
  • 7. - Case study: Dissolution profile of extended release dosage form Time (h) 0 2 4 6 8 10 Theophyllinereleased(%) 0 20 40 60 80 100 S1 S2 S3 0.50% NaCMC (w/w) Time (h) 0 2 4 6 8 10 Theophyllinereleased(%) 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 bS1 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.