[5 -1]
THE EFFECT OF SOLUTE AND MEMBRANE POLARITY IN CREATING A
PSEUDO-ZERO-ORDER CONTROLLED RELEASE PROCESS Ruchita Balasubramanian, Sakshum Chadha, Charmaine Chew, Joseph Da, Sona Dadhania,
Abhinav Karale, Grace Kresge, Meilin Lu, Victoria Ou, Ram Vellanki, Peter Zhou
Advisor: Dr. David Cincotta
Assistant: Tony Chen
ABSTRACT
In a pseudo-zero-order controlled release, the rate of diffusion is independent of time and
concentration. In this experiment, the team analyzed the rate of diffusion for strong electrolytes
(NaCl and CaSO4), weak electrolytes (citric acid, ascorbic acid, and acetylsalicylic acid), and
various alcohols (propanol, ethanol, and methanol) across polymer membranes of varying
compositions of ethylene-vinyl acetate (EVA). The change of concentration in the target area
was recorded using changes in conductivity (strong electrolytes), pH (weak electrolytes), and
gravimetric analysis (alcohols). Increasing the percent composition of EVA in the films
increased the polarity of the film, which should have theoretically increased the membranes’
permeability to polar substances. The experiments showed that no ionic salts tested passed
through the membranes for up to 40% EVA composition, and only citric acid was able to diffuse
for weak electrolytes. All the moderately polar alcohols diffused successfully. These data suggest
that only substances with intermolecular forces comparable to that of EVA can dissolve into the
membrane and therefore diffuse through it.
INTRODUCTION
Zero-Order Controlled Release
Ideally, the controlled release of a specific substance should be a zero-order process,
which describes when the rate at which a substance is transported into its surroundings remains
constant and independent of the concentration. This type of process is often sought after in
pharmacy; medicines should be delivered to the body at a constant rate over a period of time.
However, this is hard to achieve in practice, as the rate of delivery often slows and ultimately
levels off with time as the concentration of the substance in the surroundings increases (1). This
concentration-dependent process is considered first-order. Achieving zero-order controlled
release requires one to disregard the concentration component and release the same amount of
substance at the same rate over time.
Active zero-order controlled release is often achieved using a mechanical pump, as in
intravenous medical fluids. However, there is an increasing urgency to achieve passive zero-
order controlled release that has no mechanical component, because mechanical pumps tend to
be large and inconvenient. Previous mechanisms for such results have included reservoir systems
in which materials diffuse constantly through a polymer matrix when placed in an aqueous
environment (1). Other mechanisms include a pseudo-zero-order release mechanism that relies
on a first-order release kept at a constant concentration through compartmentalization.
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Figure 1: Representation of Uncontrolled Release versus Controlled Release This
representation, produced by Alzet (2), shows the difference between uncontrolled release of
chemicals, as normally done by pills, and the controlled release of chemicals achieved through
pseudo-zero-order diffusion.
Zero-order processes are often sought after in medicine because to be effective, drugs
should be delivered to a patient at a constant rate. Most medicines, however, are given in doses
that create an initial spike in concentration at the time of the dose, and then fall off until the time
of the next dose (Figure 1). Occasionally this dosage system can bring the concentration of the
drug into a cytotoxic range, which can harm the patient. A zero-order controlled release
mechanism is most ideal for such situations in order to keep the medication at a therapeutic
constant (1).
Fick’s Law and Diffusion
Diffusion constitutes the movement of a specific substance through a membrane along a
concentration gradient until the process reaches equilibrium. This process is governed by Fick’s
Law of Diffusion, as stated in the equation
(1)
where J is the flux, D is the diffusion constant, and
is the change in concentration over the
thickness of the membrane. As long as the concentration of the substance remains constant, D is
proportional to the flux, and simplifies to the following equation:
(2)
In this particular equation, J is the diffusion constant, the ∆C represents the concentration
gradient, and the ∆x represents the thickness of the membrane. This equation provides the
relationship between the concentration gradient, the thickness, and the rate of diffusion. By
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maintaining a constant concentration gradient the rate of diffusion remains constant and pseudo-
zero-order controlled release is effectively achieved.
Polymer Membrane Films
Ethylene vinyl acetate (EVA) is a copolymer that was used to create the membranes used
in this experiment. It is comprised of polyethylene and vinyl acetate, which can form a uniform
polymer membrane when cast using a solution of toluene (3). This makes a semipermeable
membrane that can filter particles based on a variety of parameters, such as particle size, polarity,
crystallinity, and intermolecular forces between membrane and particle (4). This flexibility
allows us to collect a wide range of data by testing different variables.
Polarity
Polarity describes the presence of a dipole with opposite charges on each end of the
molecule. The difference of polarity between a molecule and the polymer membrane affects the
rate of diffusion across the membrane, because polar substances will only diffuse through polar
membranes and the same with nonpolar substances and membranes. This phenomenon can be
attributed to the solution-diffusion model, where the solute must first dissolve into the membrane
and then move down its concentration gradient (6). Furthermore, when the polarities of
substances are similar, the rate of diffusion across a membrane is faster, and vice versa.
Polyethylene by itself is nonpolar due to its lack of polar groups, such as acetyl or alcohol
groups (3). Increasing the concentration of vinyl acetate in ethylene vinyl acetate, EVA, (Figure
2) increases the polarity of the copolymer. As the polarity of the membrane approaches the
polarity of the solute, the diffusion rate is expected to increase (7). Since electrolytes have a net
ionic charge, a more polar membrane would allow for a greater chance of diffusion, and would
increase the rate of diffusion.
Figure 2: Structure of Polymer Membranes These polymers were used to make semi-
permeable membranes in this experiment. (a) The molecular structure of polyethylene, which is a
nonpolar molecule. (b) The molecular structure of the copolymer ethylene vinyl acetate (EVA).
EVA is made of polyethylene and vinyl acetate. Because vinyl acetate is a polar side chain, as
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the percentage of vinyl acetate increases in an EVA mixture, the polarity of the mixture increases
as well (6).
However, more polar membranes are more difficult to manage because of the adhesive
properties of pure EVA. Therefore, the concentration of EVA must be optimized to allow for the
maximum rate of diffusion without sacrificing manageability.
Adding copolymers such as polyethylene vinyl alcohol or polyethylene glycol can also
vary polarity; this would ideally allow more polar substances to diffuse through them more polar
membrane. However, in order to add these copolymers, they must be compatible with the EVA
solvent (toluene) and with the EVA itself in order to create a uniform, workable membrane (3).
Hansen Solubility Parameters
To predict which polymers could create a solution needed to cast a film, the team referred
to the Hansen Solubility Parameters by Dr. Charles Hansen. The Hansen Solubility Parameters
describes all molecules in terms of their primary intermolecular forces: dispersion forces, dipole-
dipole interactions, and hydrogen bonding. A molecule, with its collection of the three
intermolecular interactions, can be mapped as a spherical volume on a three-dimensional plane
based on the values of the forces (8).
An equation developed by Dr. Klemen Skaarup calculates the solubility difference
between two molecules given their respective solubility parameter components (8).
(Ra)2 = 4(δD1-δD2)
2 + (δP1-δP2)
2 + (δH1-δH2)
2 (3)
The relative energy difference, or RED, is used to predict the solubility of two different
molecules. Using the Ra value calculated above, the RED can be calculated using the equation:
RED = Ra/Ro (4)
where Ro is the experimentally determined radius of the sphere of solubility for the solvating
compound (8). If the RED is less than 1, the two compounds will form a solution. If the RED is
equal to 1, the two compounds will be partially soluble with one another. If the RED is greater
than 1, the two compounds will not form a solution.
The Hansen Solubility Parameters are an attempt to quantify and predict solubility and
may not always be accurate. Solutions were experimentally tested in order to support or refute its
predicted solubility (8).
Previous Research
Team 5 of the New Jersey Governor’s School in the Sciences has been experimenting
with controlled release kinetics for several years. The 2012 team diffused saturated citric acid
through two different types of membranes: 10% EVA and 12% EVA (7). The concentration and
diffusion of citric acid was kept constant due to the continuous dissolution of the extraneous
solid citric acid added to the saturated solution. The solid citric acid continuously dissolved into
the saturated solution as the aqueous solution diffused across the membrane, maintaining a
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constant saturated concentration. Although there were some inconsistencies in their data, the
2012 team showed that it was possible to achieve a controlled release using this method (7).
However, during their first experiment, the team found that NaCl and maleic solutions were
unusable as solutes due to their irregular diffusion rates through the 10% EVA film. In 2013, the
team started to produce EVA films as opposed to the factory-made ones in 2012 (5). EVA was
dissolved into solutions; 12% EVA was dissolved in xylene while 25% and 40% EVA were
dissolved in toluene. Films were casted onto silicon paper attached to glass, and a doctor blade
was used to ensure consistency for width of the film. The 2013 team performed experiments that
tested the effects of polarity and crystallinity; they concluded that non-polar substances will
diffuse through polymer membranes using a vapor pressure analysis (5).
Hypothesis
A semi-permeable polymer membrane can be used to model the diffusion of a substance
(electrolytes or alcohols) with a controlled constant concentration at pseudo-zero-order
controlled release. Furthermore, increasing the membrane polarity will allow more polar
molecules to dissolve into the membrane and therefore diffuse down the concentration gradient
at a faster rate.
METHODS & MATERIALS
Membranes
For this experiment, it was essential to adjust the polarity of a membrane in order to
control the rate of diffusion. EVA is a copolymer composed of two monomers, ethylene and
vinyl acetate. Ethylene is a nonpolar molecule, while vinyl acetate is a polar molecule. The
varied monomers give EVA an interesting property; the regions with ethylene are nonpolar while
the regions with vinyl acetate are polar. By increasing the percentage of vinyl acetate in a
membrane, the polarity of the membrane increases. Therefore, in order to change the polarity of
the membranes, the percentage of vinyl acetate can be increased or decreased (5).
Several semipermeable EVA membranes were created with percentages of vinyl acetate
varying from 25 to 40%. In order to increase polarity, there was speculation about the addition of
99%+ Polyvinyl Alcohol (PVA) in low concentrations to allow electrolytes to diffuse through
the membrane at a greater rate. However, a proper solvent for both 40% EVA and 99%+ PVA
was not found and as a result, films were not made with PVA additive. The application of
Hansen Solubility Parameters further confirmed that PVA and EVA are incompatible in terms of
solubility. In addition to the potential of PVA, there was also potential for polyethylene glycol
(PEG) to serve as an additive to the membrane. Both a 1:2 mass ratio of PEG to EVA in addition
to a 50% solid solution of PEG and a lower percentage by solids of EVA have been tested for
membrane integrity and evenness. All films containing PEG had more cracks than membranes
containing only EVA, and also displayed clusters of PEG due to its low molecular weight. As a
result, varying concentrations of membranes containing only EVA were used to create
membranes.
Several techniques exist to create membranes. In this experiment, a mixture of 30% EVA
by mass was dissolved with toluene in order to create a gel-like substance. This solution was
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loaded into a Doctor Blade, an apparatus used to cast the film at a uniform thickness. The Doctor
Blade could produce films at 25, 30, 40, and 50 thousandths of an inch in thickness, which
allowed the team to create versatile membranes.
Prior to being loaded, however, it was determined through trial and error that the mixture
of EVA and toluene had to be stirred rapidly and subjected to heat to prevent the mixture from
solidifying. This was accomplished by occasionally heating the covered solution.
In order to cast the film, a sheet of release paper was clipped onto a sheet of glass to
provide a flat surface. The Doctor Blade was then set to the appropriate width, and the solution
was slowly poured into the Doctor Blade as it was dragged across the release sheet to create an
even film. Through experimentation, it was also determined that the Doctor Blade and release
paper needed to be heated to prevent the liquid from solidifying as it was poured into the Doctor
Blade. This was accomplished by placing the Doctor Blade and release paper into an oven that
was heated to approximately 80 degrees Celsius before use.
The membranes themselves had two properties that could be tested; polarity and
thickness. However, dealing with two variables in the membrane proved to be difficult in
experimentation, and thicknesses lower than 40 thousandths of an inch proved to exhibit more
pinholes and more stickiness than 40 thousandths of an inch. Therefore, thickness was kept
constant at 40 thousandths of an inch. Only membranes of various polarities (30%, 35%, or 40%
EVA) were tested with various solutes.
Solutions
Choosing Electrolytic Solutions
In order to test the capacity of a membrane to achieve pseudo-zero order kinetics, it is
important to use a solute that allows for a slow release mechanism. The experiment required the
creation of a saturated solution in the petri dish. The following solutes were chosen and tested in
the apparatus:
NaCl: This highly soluble ionic compound is relatively small in size and has some
medical applications in that 0.9% sodium chloride is the most common intravenous
medical infusion solution.
CaSO4: Although it is still considered a strong electrolyte, it is less soluble and has less
intramolecular ionic attractions as most highly soluble electrolytes.
Acetylsalicylic Acid (Aspirin): This molecule has a lower solubility and polarity that
should make it diffuse more easily. It also has medical applications.
Ascorbic Acid: This is highly polar and more soluble in comparison to other organic
weak electrolytes, but should still diffuse efficiently through a polymer membrane.
Citric Acid: This is a much more polar weak organic electrolyte, so this should display
the variation between molecules of varying polarity.
[5 -7]
All the weak organic acids have a similar size and molecular mass, so any change in diffusion
rate should be strictly based on solute and membrane polarity.
After creating saturated solutions from these solutes, the solid solute particles in the
saturated solution effectively replenished the diffused solute particles by consistently dissolving
into the solution until the saturation point was reached. This system maintained a constant
concentration gradient in the petri dish and thus achieved pseudo-zero-order kinetics in
accordance with Fick’s Law.
Choosing Alcohols to test with Gravimetric Analysis
In a test to determine if mostly nonpolar substances would diffuse through a polymer
membrane, certain alcohols with high vapor pressures and low boiling points were also tested
using a gravimetric analysis of vapor pressures. Since the vapor pressure of a liquid in a closed
container is kept constant at a constant temperature, it will still establish an analogous
concentration gradient as that of a saturated aqueous solution, in which the evaporated vapor will
diffuse through the polymer membrane at a constant rate. The following organic alcohols were
tested using vapor pressure gravimetric analysis:
Methanol: Methanol is a very small and polar organic alcohol that should diffuse through
a polymer membrane rather easily. It has a high vapor pressure (13.02kPa at 20°C), and a
low boiling point such that it can form a distinct concentration gradient.
Ethanol: Although it is still polar, this molecule is much larger and has a lower vapor
pressure (5.95kPa at 20°C). It has a lower polarity, so it should diffuse more easily
through less polar membranes.
Propanol: This is a mostly non-polar molecule with a slightly polar hydroxyl group on a
larger molecule. It also has a much lower vapor pressure, so it should diffuse faster
through less polar membranes.
Because the team used pure alcohols for diffusion, vapor pressures were kept constant by
Raoult’s Law. Thus, any amount that diffuses out of the container through the membrane will be
replaced by the evaporation of the liquid, keeping a constant concentration gradient of the
gaseous alcohol across the membrane. This will correlate to pseudo-zero-order controlled release
according to Fick’s Law.
Apparatus
The stable apparatus suspended the petri-dish/membrane mechanism in the reservoir
beaker at a chosen height. Using two straight wires, the team created a cage for the petri-dish
(Figure 3). The wire segments were intentionally longer than the diameter of the reservoir to
bend them over the reservoir edges and maintain further stability. Also, the hanging wire could
be adjusted for any height in the reservoir. Then, initially with silicon glue, the team fastened the
membrane to the petri-dish. However, it was later determined that the silicon glue released
ammonia, which affected the pH readings. As a result, the team substituted the silicon glue with
the 40% EVA polymer as a glue. The part of the cage that was below the petri-dish was slightly
[5 -8]
depressed, so that it did not touch the membrane itself. The entire mechanism, pictured below,
was inserted into the reservoir. To create the concentration gradient between the solution in the
petri dish and the reservoir, the apparatus was adjusted such that the mechanism was barely in
contact with the water. Conductivity/pH probes were placed in the side of the reservoirs to take
measurements. Water was poured in until both the petri-dish and reservoir had the same water
level to avoid the effects of hydrostatic pressure.
Figure 3: Aqueous Diffusion Apparatus The membrane was glued to a petri dish using excess
40% EVA solution (a), and then submerged into a beaker and suspended by metal wires such
that the membrane is in contact with deionized water (b). Conductivity and/or pH probes were
placed into the beaker and connected to a Vernier device (c) so data could be collected over time.
Gravimetric Vapor Pressure Apparatus
A similar apparatus was also used to prepare the alcohols for gravimetric vapor pressure
analysis. About 25 mL of the selected alcohol was sealed into a plastic petri dish using liquid
EVA as an adhesive, thus creating a closed container with a constant vapor pressure. The petri
dishes were kept in an incubation oven at a constant temperature of 30°C. The entire apparatus
was massed periodically so as to plot the change in mass in the container, which directly
correlates to the rate of diffusion over time.
[5 -9]
Measurements
Conductivity/pH
Because the dissociated ions of the electrolytic solutes had charge, their presence after
diffusing through the membrane could be detected by a Vernier conductivity probe. A maximum
of four probes were connected to a Vernier, which was set to record conductivity and/or pH
readings every 5 minutes for a maximum of 100 hours. By recording the change in conductivity
at five-minute intervals, the team could track the changing concentration of the electrolytic
solution in the reservoir. If the change in conductivity was linear, the solute diffused at a pseudo-
zero-order rate. In the case of weak electrolytic solutions (including organic acids), conductivity
could not be accurately measured because the organic molecules did not dissociate into ions to a
significant extent. Thus, pH was measured using a Vernier pH probe, because pH directly
correlated to an increase in internal concentration of the acid.
The probe had to be calibrated to the team’s electrolytic solutions because expected
reading values found online did not account for the team’s specific lab conditions. First, the pH
and conductivity probes were calibrated with stock solutions of known pH/conductivity to
maintain consistency among all of the probes. Then, the team performed serial dilutions for the
various electrolytic solutions. The maximum concentration used was 0.1M because the probe
was unable to accurately measure concentrations greater than 0.15M. The team checked the
readings for various concentrations, from 0.1M to 0.0001M. Conductivity readings in
microSiemens per centimeter were plotted against molarity on Microsoft Excel, and a line of best
fit was derived. A similar test was done for pH.
(a) Calibration Curve for Sodium Chloride
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(b) Calibration Curve for Calcium Sulfate Dihydrate
Figure 4: The Calibration Curves for Sodium Chloride and Calcium Sulfate Dihydrate These calibration curves for sodium chloride NaCl (a) and calcium sulfate dihydrate CaSO4
CaSO4 2H2O (b), which were made prior to the experiments, relate concentration of solution to
conductivity in microSiemens per centimeter. If there was an increase in concentration, the
conductivity should increase linearly.
Vapor Pressure Gravimetric Analysis
In a separate experiment, nonpolar alcohols had also been tested to diffuse through the
polymer membrane using a vapor pressure gradient. By Raoult’s Law, the vapor pressure of a
liquid in a closed container will stay constant at a constant temperature, thus creating a
concentration gradient of gaseous alcohols across the polymer membrane. The vapor will diffuse
through the polymer membrane at a constant rate, thus losing mass to the atmosphere. Hence, a
gravimetric method was used to affirm that the vapor diffused at zero-order controlled release.
The sample was massed periodically and plotted on an Excel graph to display the decrease in
mass. If the average change in mass was linear, the process occurred at zero-order controlled
release.
Technical Limitations
Membranes
Errors during the making of the membranes may lead to unexpected failures during the
experiment. Since the EVA solutions used to cast the films solidify easily at room temperature,
the solutions, along with the Doctor Blade and the glass plates, had to be kept warm at all times.
If anything was cold, the film turned out uneven or solidified during the casting process.
Sometimes, holes appeared in the films; these holes could be caused by several factors, including
drawing the films on uneven release paper. If there were air bubbles trapped in the EVA
solutions, those bubble sometimes were visible in the finished films. Also, if the films were too
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thin or sticky, they caused leakages in the apparatus. Membrane makers were very careful to
avoid these problems.
Apparatus
The wires that constructed the cages of each apparatus were not completely straight due
to the limitations of mechanical equipment. Also, the glue that held the membrane to the petri
dish did not always make the seal airtight, so some of the solution may have diffused out through
a leak. Another error in the conductivity readings could have resulted from the fact that the
apparatus could not be sealed off from its surroundings. The minimal increase in the
concentration, despite the lack of diffusion of solute through the membrane, may be a result of
the CO2 in the air reacting with water to create H2CO3.
For the pH tests, the main problem was that the pH increased, which contradicted the
predicted decrease in pH. The team later discovered that the silicon glue that bound the
membrane to the petri dish was increasing the pH of the solution by releasing NH3 into the
solution.
Thickness
Even though each slide was put into the oven with the same thickness, each was removed
from the oven at varying thicknesses because each stock solution of 30%, 35%, and 40% EVA
had slightly different amounts of toluene added. Since varying thicknesses affect the diffusion
rate of molecules, thickness is a moderately significant variable.
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RESULTS
Strong Electrolytes
(a) Kinetics of Sodium Chloride Diffusion
(b) Kinetics of Calcium Sulfate Dihydrate Diffusion
Figure 5: Strong Electrolyte Diffusion Experiments The figures refer to the change in
conductivity in the reservoir for NaCl (a) and CaSO4 2H2O (b) in microSiemens per centimeter
vs. hours. The general erratic pattern can be attributed to chatter in the conductivity probe.
Generally, this data does not display a linear increase in conductivity that would have been
present in a zero-order release.
[5 -13]
Weak Electrolytes
(a) Kinetics of Ascorbic Acid Diffusion
(b) Kinetics of Acetysalisylic Acid Diffusion
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(c) Kinetics of Citric Acid Diffusion, Experiment 1
(d) Kinetics of Citric Acid Diffusion, Experiment 2
Figure 6: Diffusion of Weak Electrolytic Solutions The increase in hydronium ion
concentrations in the beaker for ascorbic acid (a), acetylsalicylic acid (b), and citric acid (c,d)
were calculated based on the change in pH in the general reservoir. Citric acid was conducted
twice for reproducibility.
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(a) Zero Order Representation of Citric Acid Diffusion (30% EVA)
(b) Zero Order Representation of Citric Acid Diffusion (40% EVA)
Figure 7: Citric Acid Trend Lines The change in hydronium ion concentrations for citric acid
diffusing through 30% EVA membranes (a) and 40% EVA membranes (b) were shown to be a
linear. This suggests that the release of citric acid into the beaker was pseudo-zero-order rate.
[5 -16]
Gravimetric Analysis of Alcohols
Figure 8: Gravimetric Analysis of Alcohols The change in mass of alcohols was shown to be
linear, thus correlating to a constant rate of release. Hence, all alcohols are shown to successfully
model pseudo-zero-order controlled release.
DISCUSSION
The readings of NaCl were on the low range of 0-14 μS/cm and erratic, and based on
Figure 5a, NaCl also did not appreciably diffuse through the membranes. Regarding CaSO4 2H2O, the conductivity readings were on the low range of 10-30 μS/cm and extremely erratic
(Figure 5b). These results can be considered as noise, because if CaSO4 2H2O did diffuse, the
conductivity readings should have consistently increased linearly and have been at least in the
hundreds (Figure 5b). Thus, CaSO4 2H2O did not appreciably diffuse through the membranes.
The testing of NaCl and CaSO4 2H2O with several membranes composed of up to 40% EVA
yielded essentially no change in the conductivity of the solution.
Looking at Figure 6a, the lack of an increase in the concentration of hydronium ion
indicates that ascorbic acid did not diffuse through any of the membranes. Thus, ascorbic acid
does not diffuse through membranes on the range of 30-40% EVA. Acetylsalicylic acid also did
not increase in hydronium ion concentration, so acetylsalicylic acid did not diffuse through any
membranes ranging from 30% to 40% EVA (Figure 6b). The decrease of H3O+ concentration
may be attributed to off-gassing of dissolved CO2 from the water, which increased the pH. This
off-gassing is noticed slightly in the citric acid 30% EVA trial (Figure 7c).
[5 -17]
The citric acid diffusion data (Figure 6c) exhibits pseudo-zero-order controlled release as
the graph shows linear data. The R2 value for the citric acid placed in the 30% and the 40%
membranes (Figure 7a and 7b) are both above .90 after 12 hours and 5 hours
respectively. Evidently, the diffusion was pseudo-zero order since the H3O+ concentration
increased at a constant rate. Figure 6d displays another trial of citric acid that did not diffuse
through the membrane. For this second set of trials, the thickness of the dry membrane may have
prevented the citric acid from diffusing at all, since thickness may vary after the film is cast.
The citric acid diffusion data (Figure 7) exhibits pseudo-zero-order controlled release as
the graph shows linear data after approximately 5 hours.
Figure 8 displays the gravimetric tests using alcohols. All of the tests with alcohols
exhibited diffusion at a pseudo-zero-order rate because the graph displays a linear relationship.
In addition, the rate of diffusion is generally correlated with the polarity of the membranes. The
higher polarity membranes yielded larger diffusion rates.
There is one possible explanation as to why ionic salts did not diffuse. As ionic salts
dissolve, they undergo solvation and develop ion-dipole attractions with water molecules. This
may prevent salts from diffusing through the membranes. Thus, membranes can only allow ionic
salt diffusion by exhibiting stronger intermolecular forces with the solutes than the water
molecules do.
As for the weak electrolytes, citric acid, ascorbic acid, and acetylsalicylic acid mostly
differ in polarity and solubility (Figure 5).
Citric Acid Ascorbic Acid Acetylsalicylic Acid
Solubility: 147.76 g/100 mL 33.0 g/100 mL 0.30 g/100 mL
Molar mass: 192.21 g/mol 176.12 g/mol 180.16 g/mol
pKa: 2.79 4.17 3.49
Figure 9: Comparison between Citric Acid, Ascorbic Acid, and Acetylsalicylic Acid based
on structure, solubility, and acidity This figure shows the differences in structure, solubility,
and acidity between the three weak electrolytes which may explain differences in diffusion
through the membrane.
[5 -18]
Our results show that citric acid was the only weak electrolyte that diffused through the
membranes. This can be explained by the fact that citric acid is the most polar of the three
because it has three carboxylic acid groups. Its polarity may enable its dissolution and diffusion
through the membrane. In addition, citric acid is much more soluble than ascorbic acid and
acetylsalicylic acid (Figure 5), so more citric acid is present in solution than ascorbic acid or
acetylsalicylic acid. Therefore, its concentration gradient is greater and more detectable than that
of the other two acids. The concentration gradients of both ascorbic acid and acetylsalicylic acid
are so small that if they diffused, it may take weeks, or even months, for a discernible change to
be detected.
The gravimetric analysis of several organic alcohols was unique compared to both the
weak and strong electrolytes, since each of the four alcohols tested produced a zero-order rate of
diffusion. Methanol, ethanol, and propanol are significantly smaller than the electrolytes in the
proceeding experiments; this could provide an explanation as to why this group of molecules was
the only one to consistently diffuse through the EVA membrane.
CONCLUSION
Impermeability of Ionic Salts
Multiple experiments with membranes of varying polarity have provided strong evidence
against the hypothesis that ionic salts can pass across moderately polar membranes. The most
polar membrane tested, which was 40mils in thickness and 40% EVA by composition, did not
allow ionic salts to diffuse into deionized water any better than the less polar membranes tested.
Hence, these extremely polar molecules cannot diffuse through a polymer membrane regardless
of the increased membrane polarity. It is speculated that these ions were too polar in comparison
to the moderately polar membrane.
The Polarity of the Solute Influences Diffusion
Although many weak, moderately polar organic acids were tested, only citric acid could
successfully diffuse across the membrane. Citric acid, acetylsalicylic acid, and ascorbic acid had
similar molar masses but varying solubility in water. Furthermore, citric acid has a polarity
closer to that of EVA. The innate intermolecular compatibility between EVA and citric acid
allows for citric acid molecules to dissolve into the membrane, and therefore diffuse through it.
The Polarity of Alcohols is Comparable to that of EVA
Alcohols were able to diffuse through membranes of varying polarity consistently. This
can be attributed to the fact that the alcohol molecules are smaller and less polar than the weak
organic electrolyte solutions tested previously. The hydroxyl functional group is less polar than
the carboxyl group, thus the polarity of alcohols is more comparable to EVA, allowing it to
diffuse.
Zero-Order Controlled Release Can Be Achieved Through Diffusion
Methanol, ethanol, propanol, and citric acid were able to successfully diffuse through the
EVA membrane. Regardless of the percent composition of EVA, the flux of the sampled
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substance was kept at a constant rate because the concentration gradient of the selected substance
was kept constant across the membrane using saturated aqueous solutions or vapor pressure
constants. Hence, the apparatuses modeled a pseudo-zero-order controlled release process.
FUTURE STUDIES
The team found that ionic salts do not diffuse through membranes composed of up to
40% EVA, but was unable to conclude about greater polarities due to limitations of lab
equipment. It may be possible that increasing the polarity of the membrane, or even changing the
membrane composition itself, may yield positive results. Creating an ionic membrane, perhaps
through cross-linking ionic substances, may be the best method to dissolve ionic substances. It
may be important to determine if intermolecular forces between the solute and the membrane can
overcome those between the solutes and the water molecules. Finding a membrane’s polarity or
material that diffuses ionic salts would have strong applications in the medical field, especially
for the diffusion of electrolytic solutions into the body.
Moreover, the weak electrolytes used were relatively large in size, which may have
affected the diffusion rate. Future teams should consider choosing solutes that vary in molecular
size. Decreasing molecular size may increase diffusion through interstitial spaces. Using
molecules like acetic acid, which is smaller in size, may be better. Molecular size and membrane
polarity may be two variables that can be tested to determine a relationship for rate of diffusion.
Another variable to consider is membrane thickness. Thinner membranes may allow solutes to
diffuse faster. However, this variable may be difficult to test because it is not easily controllable
due to the limitations of lab equipment.
Currently, the membranes are limited to a range of 30-40% EVA because the films
cannot stay intact outside of these ranges. This issue limits the extent of our research because it is
impossible to accurately predict the behavior of solutes through polarities outside these ranges.
For example, citric acid diffuses through 12% EVA membranes and 30% EVA membranes, but
not through 40% EVA membranes. This potentially suggests that citric acid only diffuses in a
range of approximately 12-30% EVA. Thus, the high and low extremes of membrane polarity
prevent citric acid diffusion. The rate of diffusion may follow a bell curve shape with respect to
membrane polarity. Perhaps future groups should mathematically model diffusion of substances
through membranes before performing experiments. Testing this theory would require
experimenting with one solute and a wide range of membrane polarities, above 40% EVA.
It is also important that future groups can study the wide-ranging applications of zero-
order kinetics. For example, the zero-order principle can be applied in the pharmaceutical
industry to diffuse drugs at a rate that prevents underdose or overdose by supplying only a
therapeutic amount. Moreover, implementing zero-order diffusion in the agricultural industry
can allow nutrients to diffuse at a constant rate, eliminating the need to actively give nutrients to
the plants. Similarly, in the cosmetic industry, zero-order diffusion can be used to send fragrance
uniformly through a space.
Nevertheless, prior years of research have provided a myriad of results and conclusions
about zero-order rates and the diffusion of various substances through different membranes. The
team encourages future scientists to enhance this field by further learning how to diffuse ionic
[5 -20]
salts, small or large weak electrolytes, or multicomponent solutes, and seek to find an even
stronger relation between membrane polarity and diffusion rates.
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