The Effect of Drug Characteristics on Drug Delivery

Performance
N. Chakravarty, H. Hiraki, A. Sriram

INTRODUCTION
Purpose
Drug delivery is an exciting field within the biomedical sciences which is revolutionizing
patient treatment. The prospects of drug delivery systems hinge on the safety, cost-
effectiveness, and the efficacy of the system.1 This exercise serves as an introduction to the field
of drug delivery which will culminate in the fabrication of a controlled drug delivery device. In
anticipation of this design project, the effects of various design parameters on drug delivery
performance are investigated, specifically in this experiment, the effect of drug characteristics of
the alginate bead is explored.

Three drugs were tested for drug delivery efficacy: Erythrosin B, Brilliant Blue, and Tempura
Paint. Tempura Paint has a highly hydrophobic structure and had the highest molecular weight
of the molecules tested. Brilliant Blue is a polar molecule as well as the molecule with the
smallest molecular weight being tested (Fig. 1). Erythrosin B was the final molecule tested with
a low polarity and a structure slightly heavier than that of Brilliant Blue (Fig. 1).

Brilliant Blue (Blue #1) Erythrosin B (Red #3)

Figure 1. This table summarizes the chemical structures of Brilliant Blue and Erythrosin B. Tempura paint is not
included in this figure due to its large and highly complex structure.

Hypothesis
It was hypothesized that the drug with similar polarity to the solvent will cause more intense
intermolecular interactions. This coupled with a low molecular weight would allow a molecule
to have high molecular diffusion in a solvent. Thus, Brilliant Blue alginate beads were predicted
to have the fastest drug release profile in comparison to Tempura Paint and Erythrosin B given
its high polarity, similar to that of the polar solvent, and low molecular weight.
METHODS AND MATERIALS
List of Materials:
● Brilliant Blue Solution ● 20 Gauge Metal Needle x3
● Erythrosin B Solution ● Filter Paper
● Tempera Paint ● Funnel
● Alginate Salt ● Clear Cup x6
● 2% Sodium Chloride Solution ● White Paper
● 5mL Syringe x3 ● Timer
● Device to Take Photographs

Experimental Method:
1. Obtain above materials and create three stations that include a syringe, needle, and clear
cup
2. Mix three solutions of brilliant blue, erythrosin B, and tempera paint in alginate salt in
three separate clear cups
○ Concentrations between each solution should be constant
3. For each of the three drug solutions, take in 1mL solution into the 5mL syringe and
screw on the 20 gauge metal needle
4. Position the needle tip ~15cm above the sodium chloride solution and apply pressure to
the syringe to allow ‘drops’ of the drug solution to fall into the calcium chloride
○ Must be in a controlled manner as to create equal sized beads
5. Create beads using 1mL of drug solution
6. Lay the filter paper into the funnel and filter the bead/calcium chloride solution into a
collection beaker
7. Collect the beads from the filter paper
8. Repeat steps 4-7 with the remaining two drug solutions
9. Once all beads are collected, fill the three remaining clear cups with ~200mL tap water
and place them on a white piece of paper
10. Drop all beads in at once, begin a timer, and take an initial photograph of the three cups
over the white paper
11. Take pictures of the cups every three minutes for 15 minutes, then again at 25 minutes,
making sure to take a picture of a cup with no beads for negative control in image
analysis and a picture of drug solutions for positive control in image analysis.
12. Compile the images in ImageJ and run photo analysis to determine absorbance levels of
the each solution at each time

Image Analysis Method:

1. Open image in ImageJ
2. Open Measurement tool in ‘Analyze’ toolbar
3. Select area for analysis
 4. Press ‘ctrl+m’ to analyze gray value
5. Repeat for all images
6. Normalize images to negative control – picture of solvent in cup with no beads – by
subtracting measured gray value from control gray value
7. Plot against time

RESULTS
Images collected throughout the experiment indicated that Erythrosin B had the highest rate of
diffusion in comparison to Tempura Paint. Qualitative analysis of the images showed that
Tempura Paint had the lowest molecular diffusion out of the drugs tested, illustrated by little to
no change in the color of the solvent. Brilliant Blue had the second highest rate of diffusion
qualitatively speaking, turning the solvent a light blue color at the end of the 25 minute
experiment. Erythrosin B leaked from the alginate beads, turning the solvent a deep pink color
(Fig. 2).

Figure 2. A summary of the images captured during the experiment are summarized above. The color of the solvent
in each cup is an indicator of the drug delivery performance and the level of molecular diffusion. The images
qualitatively show that Erythrosin B had the highest diffusion in water out of the drugs tested.

Quantitative analysis of images using the program ImageJ corroborated the qualitative analysis.
The normalized curves of the gray values show the intensity of color in the solvent over time.
Plots for Tempura Paint and Brilliant Blue show that gray values did not change much over
time, hovering around initial values. These plots clearly show that the solvent in the cup with
Erythrosin B reached the highest color intensity (normalized gray value) over time, supporting
the claim that Erythrosin B has the most efficient drug performance and diffuses the most in
water (Fig. 3).

Effect of Drug Properties on Drug

Release Profile
Erythrosin B Brilliant Blue Tempura Paint

100
NORMALIZED TO NEGATIVE CONTROL
GRAY VALUE OF SOLUTION COLOR

80

60

40

20

0
0 5 10 15 20 25 30
-20

-40
TIME (MIN)

Figure 3. This plot shows the normalized gray values of the solvent colors for each of the drugs tested. Erythrosin B
clearly had the highest normalized gray value, thus having the highest rate of molecular diffusion and best drug
performance.

CONCLUSION
Our parameter of interest, the type of drug used in the alginate bead, had a noticeable effect on
the drug release profile. As tempura paint is known to be a quick drying and long lasting paint,
it is not surprising to see that the alginate beads loaded with it had the slowest release profile.
The water cup containing these beads had almost no color change. In comparison, Brilliant Blue
and Erythrosin B yielded drug release profiles which reflected the opposite of what was
expected based on the polarity of the molecules. It was expected that brilliant blue would show
a much faster and more intense drug release profile. However, it can be seen in Fig. 3 that
Erythrosin B had the faster drug release profile of the two.

Another group performing the same experiment concluded with results contrary to ours, which
supported initial hypotheses. This difference in results can be attributed to error and lack of
controls between lab groups. A notable source of error was the reuse of calcium chloride
solution between each type of bead fabrications as our group was given only one aliquot of
solution. After filtrating the beads from the initial Erythrosin B bead fabrication, the solution
was noticeably red in color. This solution was then used to make the Brilliant Blue beads,
becoming slightly purple in color before being used to make the Tempura Paint beads. It is easy
to see how cross-contamination could play a role in the degree of bead gelling/density between
trials. Another source of error which, in retrospect, may have contributed largely to
discrepancies between lab groups and inconsistencies in the data graphed in Fig. 3 is
inconsistencies in photography and image analysis. Each picture (Fig. 2) was taken at a different
angle and height which affected lighting in the photo and the shadows which fall across the
cups. Additionally, solvent color was not uniformly distributed in each cup, thus the areas
chosen for gray value measurement may not have been representative of the color of the entire
cup. These errors can be mitigated in the future through implementation of experimental
methods which control the variables of image collection, gray value analysis, and drug solution
fabrication.

The findings that Erythrosin B is conducive to a quick drug release profile can be used to inform
the fabrication of drug delivery systems. Systems which require a high rate of diffusion can
utilize Erythrosin B while systems which require lower rates of diffusion can employ the drug
characteristics of Brilliant Blue. In a broader context, the exploration of the effect of design
parameters on drug delivery performance can be used to engineer more informed, efficient
drug delivery systems which in turn can provide better healthcare solutions for the drug
market.

References
1. Brown, Marc B., et al. "Dermal and transdermal drug delivery systems: current and future
prospects." Drug delivery 13.3 (2006): 175-187.