Zero-Order Kinetic Release From Capsule
Reservoirs through Semi-Permeable
Polymer Membranes
Denise Bion, Matthew Blank, Dylan Freas, Craig Gambogi,
Demetris Rotsides, Sadik Shahidain, Daniel Ye, Barbara Zhan
Dr. David Cincotta, Amanda Garfinkel
Controlled-Release Kinetics
• Study of the rates of chemical
processes
•Most are naturally first or secondorder
• Zero-order reactions usually do
not occur spontaneously
• “Pseudo-zero-order reactions”
Applications of ControlledRelease Kinetics
• Very
effective
medical treatment
•Prevents drugs from
reaching near-toxic levels
(such as those in
chemotherapeutic
treatments)
• Helps maintain
safe but effective
concentrations
Polymers
• Series of repeated monomer units  long chains
• Many properties
affect permeability:
• Chain length
•Chain branching
•Intermolecular
forces
• Different properties result in different diffusion
rates
Microspheres (Nanyang Experiment)



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BSA loaded into microspheres
Drug Immobilized in PEG membrane
Microsphere acts as an unlimited reservoir
BSA diffuses over a long period of time
Fick’s Law
Fick’s Law goes against the
concept of a zero-order release
mechanism
Constant concentration 
pseudo-zero-order release
Hypothesis
Constant vapor pressure  zero-order release
Goal: To create a
zero-order release
mechanism
http://apollo.lsc.vsc.edu/classes/met130/notes/chapter7/cond_pure_sat.html
Hansen Solubility Parameters
Ra2 = 4(δ D1 - δ D2) 2 + (δ P1 - δ P2) 2 + (δ H1 - δ H2) 2
RED > 1 : Insoluble
RED < 1 : Soluble
Methods and Material
VEGETABLE
CAPSULES
Membrane
Liquid
Liquid
GEL CAPSULES
Liquid
Petri Dish
Final Experiment
Membrane
Liquid
2 mL
Petri Dish
Overview


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
3 polymer membranes, 2 organic solvents, 2
types of capsules
9 combinations of solvent, capsule, and
membrane tested
12-hour experimental window
Systems were massed every two hours
Diffusion of Acetone across Gelatin Capsules and Various
Polymer Membranes (Trial A)
1.58
12% EVA
1.56
Grams Solvent Remaining
10% EVA
1.54
PE
1.52
Linear (12%
EVA)
R2 = 0.682
Linear (10%
EVA)
1.5
R² = 0.8083
Linear (PE)
R² = 0.926
1.48
0
2
4
6
Time Elapsed (Hours)
8
10
12
Diffusion of Pentane across Gelatin Capsules and Various
Polymer Membranes (Trial B)
1.3
12% EVA
1.25
10% EVA
Grams Solvent Remaining
1.2
PE
1.15
1.1
Linear (12%
EVA)
R² = 0.9762
1.05
Linear (10%
EVA)
1
R² = 0.878
Linear (PE)
0.95
R² = 0.9742
0.9
0
2
4
6
Time Elapsed (Hours)
8
10
12
Diffusion of Pentane across Pullulan Capsules and
Various Polymer Membranes (Trial B)
1.3
12% EVA
1.25
10% EVA
1.2
Grams Solvent Remaining
1.15
PE
1.1
1.05
Linear
(12% EVA)
1
R² = 0.9822
Linear
(10% EVA)
0.95
R² = 0.7352
Linear (PE)
0.9
R² = 0.9395
0.85
0.8
0
2
4
6
Time Elapsed (Hours)
8
10
12
Error Analysis
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Rubber band flaw
Cool down every two hours for massing
Excess membrane
Few data points due to long duration of
diffusion
Conclusion
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Pseudo-zero-order release w/ capsules and
membrane is possible
Many combinations exhibited strong, linear
releases
Our model justifies microsphere experiment
Future Studies

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Capsules relevant to biological systems
Further experiments on controlling rate of
release
Acknowledgements
Dr. David Cincotta, advisor
 Amanda Garfinkel, assistant
 Dr. David Miyamoto, director
 NJGSS and sponsors, providing the

opportunity for this experience