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 second-order

• Zero-order reactions usually do not occur spontaneously

• “Pseudo-zero-order reactions”

Applications of Controlled-Release 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)

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

Constant concentration pseudo-zero-order release

Fick’s Law goes against the concept of a zero-order release mechanism

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 : InsolubleRED < 1 : Soluble

Methods and Material

VEGETABLE CAPSULES

GEL CAPSULES

Petri Dish

Membrane

LiquidLiquid

Liquid

Final Experiment

Petri Dish

Membrane

Liquid

2 mL

Overview 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

0 2 4 6 8 10 121.48

1.5

1.52

1.54

1.56

1.58

R² = 0.925985951345299

R² = 0.808331055956662R² = 0.681997552522909

Diffusion of Acetone across Gelatin Capsules and Various Polymer Membranes (Trial A)

12% EVA

Linear (12% EVA)

10% EVA

Linear (10% EVA)

PE

Linear (PE)

Time Elapsed (Hours)

Gra

ms

Solv

ent

Rem

ain

ing

0 2 4 6 8 10 120.9

0.95

1

1.05

1.1

1.15

1.2

1.25

1.3

R² = 0.974217178153149

R² = 0.877973152484053

R² = 0.976239449903202

Diffusion of Pentane across Gelatin Capsules and Various Polymer Membranes (Trial B)

12% EVA

Linear (12% EVA)

10% EVA

Linear (10% EVA)

PE

Linear (PE)

Time Elapsed (Hours)

Gra

ms

Solv

ent

Rem

ain

ing

0 2 4 6 8 10 120.8

0.85

0.9

0.95

1

1.05

1.1

1.15

1.2

1.25

1.3

R² = 0.939515159909512

R² = 0.735221868707948

R² = 0.982246326271117

Diffusion of Pentane across Pullulan Capsules and Various Polymer Membranes (Trial B)

12% EVA

Linear (12% EVA)

10% EVA

Linear (10% EVA)

PE

Linear (PE)

Time Elapsed (Hours)

Gra

ms

Solv

ent

Rem

ain

ing

Error Analysis Rubber band flaw Cool down every two hours for massing Excess membrane Few data points due to long duration of

diffusion

Conclusion Pseudo-zero-order release w/ capsules

and membrane is possible Many combinations exhibited strong,

linear releases Our model justifies microsphere

experiment

Future Studies Capsules relevant to biological systems Further experiments on controlling rate

of release

Dr. David Cincotta, advisor

Amanda Garfinkel, assistant

Dr. David Miyamoto, director

NJGSS and sponsors, providing the opportunity for this experience

Acknowledgements