Dynamic Colon Model
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Transcript of Dynamic Colon Model
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.