1. Advisor: Dr. David Cincotta Assistant: Stephanie Hojsak
Controlled Release Kinetics: Modeling Small Molecule Movement Across a Polymer Membrane
Tyler Barna, Ella Glenn, Lawrence Huang, Richard Huisa, Dongmin Kim, Ellen Li, Tina Lu, Thomas Mazumder, Anjali Nambrath, Catherine Ryczek, Aditya Shah, Yulan Zhang
Advisor: Dr. David Cincotta Assistant: Stephanie Hojsak

2. Controlled Release Kinetics
Aditya- Define control release. I’ll state how it is applied in every day life. And ill explain its impacts when dealing with drugs.
Mention fluctuations more -- they’re problematic because
Mention blood stream...metabolised/ filtered out
Also, fertilizer is an application, dumping fertilizer and killing crop or constantly releasing some fertilizer over time
Recreate graphs
All caps is bad
The goal of controlled release is constant release over time
Concentration of drug in the blood rises quickly close to toxic levels
Concentration decreases over time because it is metabolized, filtered out of blood, etc
This is also true of air freshener… it gets consumed

3. Pseudo-Zero Order Process
Richie
In this slide we should cover kinetics of reactions, different kind of reactions and how changes in concentration don’t matter in zero-order
I will also cover the whole “pseudo prefix” blah blah :)
Replace “trendline” with “constant slope over

4. EVA: poly(ethylene vinyl acetate)
A copolymer made of thousands of units of ethylene and vinyl acetate monomers
EVA is selectively permeable
Ethylene m
Vinyl acetate
Yulan
Started talking about wt% then went to mol% -- no clarity about the change
Move before fick’s law
Talk about higher / lower polarity -- what property changes with changing va%
Use skeletal diagrams -- comparison of size would be nice too
Didn’t mention hydrogen bonding
Difference between ethylene and VA, but also has the capability to create a hydrogen bond with other compounds
More polar
Mention dispersion forces
Bigger vinyl acetate -- emphasizes difficulty in crystallization
1:15
Our project focused on the controlled release of gases through a poly(ethylene vinyl acetate) (or EVA) membrane. Poly(EVA) is a copolymer made of ethylene and vinyl acetate monomers.
Ethylene is a nonpolar molecule whose primary IMFs are dispersion forces. On the other hand, VA, which is polar, interacts more through dipole-dipole interactions and is also capable of forming hydrogen bonds with other compounds (not with itself.) Thus, increasing % VA would increase the overall polarity of the membrane. Moreover, ethylene regions of the membrane tend to be very rigid and crystalline, meaning that it is difficult for molecules to diffuse through these areas. Vinyl acetate regions, on the other hand, are amorphous, making it easier for molecules to diffuse through these areas.
[note from thomas:] Also, in terms of physical structure, vinyl acetate portions of the membrane are amorphous, and ethylene portions are crystaline, which is much more rigidly packed and harder to dissolve in/diffuse through.

5. Fick’s Law of Diffusion
Chemical potential ∝
Diffusion flux
mol/(m2hr)
concentration gradient
mol/m3 ∂𝜑 -D J ⋅ = ∂x
Membrane thickness m
Diffusion coefficient
m2/hr
Yulan
Diff coeff depends etc. not necessary
Membrane-- what is? --we dunno
Be more general -- use original partials form
Diffusion coefficient is not diffusion rate -- “fudge factor”
Diffusion flux once, then just flux
1:00 - change slide
Also talk about what this number means (what it means in our data)
In order to conduct a quantitative analysis of different compounds’ diffusion through the EVA membrane, we used Fick’s Law of Diffusion. Fick’s Law of Diffusion relates diffusion flux, the amount of compound that diffuses through each unit area of membrane per unit time, to the diffusion coefficient and the derivative of chemical potential with respect to position. Chemical potential is directly proportional to concentration gradient, and position is analogous to membrane thickness, so the derivative is essentially change in concentration across the membrane divided by membrane thickness. The diffusion coefficient is a constant that represents the relative diffusion rate of a substance. In other words, a compounds with higher diffusion coefficients will diffuse faster.

6. Fick’s Law of Diffusion Rearranged
Membrane thickness
Rate of
Diffusion
Diffusion Coefficient (D) ΔX = ⋅ A ΔC
Concentration gradient across membrane
Membrane area
Yulan
X for multiplication or variable
Put A under rate → rate per area normalizes that term
Thickness per concentration is inverse of gradient
This is Fick’s Law of Diffusion simplified and rearranged to solve for the diffusion coefficient.

7. Membrane Diffusion Tested system: Sealed Jar
Chemical Introduced to System
Evaporation in System
Dissolution in Membrane
Evaporation to Surroundings
Tested system: Sealed Jar
Surroundings: Open Laboratory
Barna
Equilibrium is established during evaporation, creating constant vapor pressure and, therefore, constant chemical potential
The dissolution within the membrane is the rate limiting step that allows for a zero order process
The molecule, dissolved at local amorphous points of the membrane, or bounces off of crystalline points
Mention Chemical continually dissolving and then evaporating through the membrane until it reaches the surroundings
Pass through -- dissolve, redissolve until it gets out into surroundings

8. Chemical Variables Chemicals have different volatility
Chemicals have a variety of polarities
Chemicals possess unique sizes, structures
Unique properties of each chemical result in different interactions and different measured rates of diffusion.
Barna
Volatility correlates directly with chemical potential
Chemicals have unique size structures → SUGGESTS SHAPE → affects speed with which molecule goes through (ex: increased size, same polarity, takes longer to completely diffuse)

9. Hansen Solubility Parameters
“Like dissolves like”
𝛿P = polarity 𝛿D = dispersion 𝛿H = hydrogen-bonding
Ra measures how “different” compounds are
Ra = 4(𝛿D2 - 𝛿D1)2 + (𝛿P2 - 𝛿P1)2 + (𝛿H2 - 𝛿H1)2
Ellen
Make it clear that delta describes the solubility parameters
What are d1 and d2 in the subscripts in Ra equation
Emphasize distance
“Like dissolves like”
--polar solvents and polar solutes,
Nonpolar solvents and nonpolar solutes.
A way to model this phenomenon and predict compound solubility is with HSP.
Compounds are assigned experimentally determined parameters

10. Hansen Solubility Parameters
Alcohols 𝛿H
EVA
Alkanes 𝛿D
Ellen
Smaller Ra -- closer to each other in space -- more likely to dissolve
Give an example about how to interpret this -- this is close to eva, should diffuse well
Remove legend, scale up graph, label dots directly 𝛿P

11. Hypotheses Higher molecule-membrane compatibility
Predicted by Hansen
Solubility Parameters
Hypotheses
Higher molecule-membrane compatibility
Higher vinyl acetate composition of membrane
Catherine
The hypothesis needs to be clear
What you know
What you think you know
What you predict
**Rate limiting step is dissolution into membrane**
The main idea of our hypothesis and general approach to this project was based upon the idea that for a gas to diffusion through a membrane, it must first dissolve. With this in mind, we predicted that the diffusion coefficients of the chemicals will increase as the molecule-membrane compatibility increases. This means that compounds with similar intermolecular to the membrane will most easily diffuse. This compatibility is predicted by Hansen Solubility Parameters.
One of these key characteristic is polarity. Therefore, we predicted that as the vinyl acetate composition of the EVA membrane increased (making the membrane more polar), the diffusion coefficient would increase.
Larger Diffusion Coefficient

12. EVA Membrane Production
Solutions
Courtney
Too much time on this slide
Polymer is not melted, it is dissolved
Picture of dissolution is not necessary?
Need to include:
9.80% Vinyl Acetate and 13.3% Vinyl Acetate
Casting
More vinyl Acetate means stickier and less means cracking
In order for our hypothesis to be tested, we needed membranes. We made 2 membranes to be tested. The first membrane we made was 9.80% by molar composition of Vinyl Acetate and 13.3% Vinyl Acetate. The EVA beads were dissolved in toluene to produce a clear, homogenous solution.

13. EVA Membrane Production
Solutions
Casting
Courtney
Cast the membrane not pull the membrane
Membrane need to be dried -- 24h in the drying oven
Minimize and eliminate
Need to include:
9.80% Vinyl Acetate and 13.3% Vinyl Acetate
Casting
Next, we casted the membranes. We used the calander to produce a uniform thickness in membrane. We pulled the calander slowly to minimize the bubbles.
We used a calander to make a membrane that was uniform in density and thickness. We would pour the membrane solution and drag the calander slowly to decrease the bubble and hole formation in the membrane

14. EVA Membrane Production
Solutions
Casting
Inspection
Courtney
Need to include:
9.80% Vinyl Acetate and 13.3% Vinyl Acetate
Casting
After 24 hours in a drying oven, we check them under the microscope for small holes. We placed the x to avoid the holes

15. EVA Membrane Production
Solutions
Casting
Inspection
Membrane placement
Courtney
Need to include:
9.80% Vinyl Acetate and 13.3% Vinyl Acetate
Casting
Calculate surface areas of the membrane, which we can use to measure the thickness of the membrane
The last step was putting the membranes on the mason jars. We kept the membrane surface area constant to measure the thickness. Next, we placed the membranes on top of the mason jars and closed the caps without producing any wrinkles that could negatively affect the data.

16. Raw Data Collection Thomas Drop propylamine 19 compounds tested
Talk about the linear regression stuff (r^2) and its importance, and also why we suspect propylamine is funky
19 chemicals testing
R^2 is the measure of fit to the data points
“All 18 fit” -- focus on the ones that worked
Ditch definition of R2 value
Minimal discussion of # successes
Little bit of curve at the beginning -- someone might ask abt this at the end
PSEUDO zero order not zero order

17. Hansen Solubility Parameters
Tina
Remind what Ra is
*****Too close to the microphone
Slow down a bit -- started at a good speed and then sped up
The fact that the slope is negative is significant (not a coincidence)
Plot difference in h-bond parameter, diffusion coefficient
Say solubility not compatible b/c compatible means different things in different situations
Get rid of some zeroes on y axis
Make numbers easier to read (axes, R2 values)
Speaker notes:
These graphs display the effect of the Hansen Solubility Parameters on our data. Recall from before that Ra values are a measure of the compatibility of the compounds with the membrane. Lower Ra values indicate greater compatibility.
So as you can see from these graphs, both of the slopes relating the Ra’s and diffusion coefficients are negative. After running a linear regression t test on slope, we were able to conclude that these two negative slopes are statistically significant on the alpha = 0.05 level.
Thus, we were able to conclude that as the Ra value increases, the diffusion coefficient tends to decrease. In other words, the more compatible the compound was with the membrane, the more easily the compound diffused across the membrane, supporting our initial hypothesis.
We also investigated the effect of specific parameters on the diffusion coefficient. Recall that the three parameters that make up the Hansen solubility parameters are dispersion, hydrogen bonding, and polarity. We found that polarity had the greatest effect on the diffusion coefficient while dispersion had the least effect.

18. Increasing dipole moment
Effect of Compound Polarity and Membrane Composition on Diffusion Coefficients (D)
Better D with 13.3% VA
Better D with 9.8% VA
D 13.3% VA
D 9.8% VA
Increasing dipole moment
Anjali
Compound names a little unclear
Crossed lines looked solid
Delete “Compounds Tested”
“Effect of Chemical Polarity and Membrane Composition”

19. Effect of Functional Groups for 9.8% VA
Lawrence
Fix axes values
Functional groups
Talk about how within each functional group, D increases with mass because of polarizability - confirms Hansen Solubility Parameters
-alkanes/esters predicted to dissolve the most in the membrane, most diffusion
Dispersion forces are weighted more in Hansen, shown b/c the alkanes(least polar but highest molar mass) had the highest average diffusion coefficient of the family

20. Effect of Functional Groups for 13.3% VA
On average, all compounds diffused more easily through the membrane with the higher VA percentage
Fits hypothesis that more amorphous regions from greater VA percentage
Noticeable increase for more polar compounds (amines, ketones, esters, alcohols)
13.3% membrane had more polar and amorphous regions… (shorter intro)
Fix axes values

21. Potential Future Research
Liquid-liquid diffusion of aqueous solutes
Vapor-gas diffusion of mixtures
By diversifying the compounds investigated, a more complete picture of pseudo-zero order can be achieved.By diversifying the compounds investigated, a more complete picture of pseudo-zero order can be achieved.Ella

22. Acknowledgements Special Thanks to: Novartis Overdeck Foundation
State of New Jersey
Mango Concept
Independent College Fund of New Jersey
Johnson & Johnson
Allergan
Novartis
Celgene
NJGSS Alumni and Parents
NJGSS
Dr. Cincotta
Steph Hojsak
Sydney Li and Bogac Kerem Goksel