HL Chemistry Internal Assessment Candidate Number: XXXXXX-0001

Examination Session: May 2023 Candidate Code: jtj551

RESEARCH QUESTION: What is the effect of pH (2, 4, 6, 8, 10) on the rate

of degradation of Ibuprofen measured by the change in absorbance (AU) using a
UV Visible Spectrophotometer?

Rationale

Ibuprofen was serendipitously discovered by Stewart Adams in 1971 after he tested it on his
headache. Reading about this accidental discovery led me to research Ibuprofen’s properties.
Scientists know that a drug's most common observed factor is its degradation. How it
interacts with its environment, how it reacts to external and internal factors and most
importantly how it reacts in the human body are all necessary situations to take into
consideration.

This degradation study is crucial for a variety of reasons, including (a) that it is an essential
analytical component of drug development, (b) that it offers insightful data on drug release
behaviour, and (c) that it makes it easier to analyze the chemical and physical stability of
drug substances and drug products (Husain, 2016). Studying the degradation of Ibuprofen is
important as this is a common anti-inflammatory used for our body and hence its instability
can have detrimental effects leading to this research question. Furthermore, pH is not only an
external factor but an important internal factor considering the tightly controlled blood pH
and low pH in the stomach. Investigation of Ibuprofen’s interaction with varying pH values
can provide important information about the drug and its use.

Background Information
1. Ibuprofen

Ibuprofen is a commonly used nonsteroidal anti-inflammatory (NSAID). In this structure, the

aliphatic carboxylic group is para position to the alkyl substituent. It is a colourless,
crystalline substance with a distinctive odour that serves as a non-steroidal anti-inflammatory
medication and a non-narcotic analgesic (PubChem, 2019). It is a very prevalent Non-
prescription drug that is used extensively as an analgesic, an anti-inflammatory, and an
antipyretic (Arch Int Pharmacodyn Ther, 1969).

Figure 1: Chemical Structure of Ibuprofen

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HL Chemistry Internal Assessment Candidate Number: XXXXXX-0001
Examination Session: May 2023 Candidate Code: jtj551
2. Effect of pH on Ibuprofen
Ibuprofen degrades when subjected to a high pH with a direct relationship and correlation.
More the initial pH, higher the Ibuprofen degradation. The functional group of ibuprofen has
a dipolar character and is made up of hydrophilic and hydrophobic moieties. According to the
research (Iovino et al., 2016), the hydrophilic part of this molecule degrades when exposed to
factors like pH. The degradation reaction is assumed to be an equilibrium reaction with
Ibuprofen’s anionic and molecular forms. According to Le Chatelier's principle, the
equilibrium shifts to the right to increase the concentration of H+ ions when the pH rises
since an increase in pH causes a reduction in the concentration of H+ ions. As the pH
decreases, the concentration of H+ ions increases shifting the equilibrium position to the left.
Since the Hydrophilic part (anionic form ) of Ibuprofen degrades, an increase in pH thus
increases the degradation of the Ibuprofen molecule. Figure 2 demonstrates this equilibrium
reaction (Dwivedi et al., 2011).

Figure 2: Equilibrium Reaction showing Degradation of Ibuprofen

To quantify the degradation of Ibuprofen the following formula was used:

Figure 3: Degradation Rate Formula

where,
A0 =initial absorbance
At =final absorbance

Hypothesis

Hypothesis: Increasing the pH will cause an increase in the change in absorbance (AU) and
hence increase the rate of degradation (%) of Ibuprofen.
Variables
Independent Variable: pH (pH units) of Ibuprofen in the range of 2, 4, 6, 8 and 10. A
preliminary trial determined the range using a pH probe and Vernier Graphical Analysis
software. Increasing the pH from 2 to 10 should hypothetically increase the rate of
degradation (%).

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Dependent Variable: The degradation rate of Ibuprofen measured by the change in
absorbance values (AU). By using 5v5 trials, measurements were taken using a UV-visible
spectrophotometer. This experiment employed the degradation rate as a quantitative way to
evaluate how pH affects the stability of ibuprofen.
Controlled Variables:
Table 1:The controlled variables of this investigation
Variable Why you need to control How the variable will be
it controlled
Temperature Ibuprofen can also A temperature-
degrade at higher controlled water bath at
temperatures like 37°C as it is the most
250°C(Akay et al., stable at this temperature
2021). Hence, it would
be unclear whether the
degradation is due to pH
or Temperature.
Concentration of Varying concentrations One stock solution was
Ibuprofen solution would vary the amount prepared and used for all
of Ibuprofen in the trials. Concentration was
solution which would accurately measured
react differently with using a measuring
pH. Hence, the effect of cylinder.
pH would be unclear,
and a proper conclusion
may not be reached.
Duration of each trial Time is one of the 10 minutes was taken as
variables that can affect the accurate duration
the degradation rate and after experimenting with
hence would not provide 5 and 15 minutes. It was
a reliable comparison. controlled using a
stopwatch.
Light Light intensity could be Ibuprofen was kept in a
one of the factors cool dark spot in
affecting rate of cupboard, shielded from
degradation and can intense artificial or
interfere with this natural light.
investigation (Iovino et
al., 2016b).
Concentration of HCl Different concentrations 1M HCl was taken from
of HCl have different the correctly labelled
concentrations of H+ container.
ions and hence affect the
degradation of
Ibuprofen. It would be
unclear if the
degradation was from
temperature or pH.

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Materials
Table 2: Showing the Apparatus/chemicals used with their quantity and uncertainty

Apparatus/Chemicals Quantity Uncertainty

Vernier UV Visible Spectrophotometer 1  0.001 AU
Magnetic stirrer 1
Magnetic plate 1
cm3 Droppers 1
pH meter and Probe (Vernier GoDirect 1  0.2 pH units
Electrode Amplifier, ID: 061096P2)
Stopwatch 1
100mL Volumetric flask  0.08 mL

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Data Logger Analysis software (Vernier 1
Spectral Analysis
Glass bottle 1
Glass rod 1
Whatman No.1 Filter Paper 1
50 mL beaker 2
100 mL beaker 2
Clamp Stands 2
Vernier Graphical Analysis software 1
Mortar and Pestle 1
Electronic Weighing scale 1  0.005g
Temperature-controlled water bath 1
HCl 1M
Ibuprofen Tablets: Nurofen 200 mg
Distilled water
NaOH 0.1N
NaOH 1M

Preliminary Experimentation

A Preliminary Trial was conducted to determine the range of pH values and test the
preparation of Ibuprofen. Ibuprofen was dissolved in ethanol, sodium hydroxide and water to
test its solubility and determine the solvent which was the most suitable for the experiment.
Sodium Hydroxide was found to be the suitable solvent where Ibuprofen was most soluble
and hence was chosen. The highest and lowest pH values were manipulated and tested to
determine the range and see the effect on Ibuprofen. A trial experiment was conducted with
pH 2 and pH 12 to observe a difference and hence define the approach of the main
experiment. Upon recording the absorbance values, a significant difference was observed
between pH 2 and pH 12 indicating a strong correlation. The setup was created and tested and
absorbance values were recorded at 5, 10 and 15 minutes to test its effect. It was observed
that at 5 mins, there was too little effect and at 15 minutes it was too long of a duration, hence
10 minutes was taken as the final duration. The values, 2, 4, 6, 8 and 10 were chosen as it
covers almost all the values on the scale. The initial absorbance value of Ibuprofen was
measured using the spectrophotometer and noted to be 0.731 AU so it can be compared with
the final absorbance values after exposure to the pH values.

Methodology

1. Preparation of Ibuprofen stock solution

(a) One Nurofen Ibuprofen tablet containing 200mg of Ibuprofen was crushed using a
mortar and pestle
(b) 0.1g of the crushed drug was accurately weighed using the electronic weighing
balance and stored in a plastic cup.
(c) This powder was transferred to a 20 mL beaker with 0.1 N sodium hydroxide and
stirred using a magnetic stirrer for 15 minutes to dissolve the Ibuprofen.
(d) This dissolved solution was transferred to a 100 ml volumetric flask, and the
remaining volume was filled with 0.1 N sodium hydroxide. (Hapse et al., 2011)

2. Calibration of pH meter

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HL Chemistry Internal Assessment Candidate Number: XXXXXX-0001
Examination Session: May 2023 Candidate Code: jtj551
(a) Distilled water was used to rinse the electrode.
(b) Kim wipes were used to blot it dry.
(c) The electrode was put in a buffer with a pH of 4 and was allowed to stabilize for
minutes using the Vernier Graphical Analysis software.
(d) The pH meter was set after stabilization and the electrode was rinsed.
(e) Steps (b) and (c) were repeated for pH 7 and pH 10.
(wikiHow, 2008)

3. Experiment
(a) 15 mL of the stock solution of Ibuprofen was added to a beaker and placed on a
magnetic plate with the magnetic stirrer.
(b) A Clamp stand was used to hold the pH meter above the beaker, with the electrode
submerged in the Ibuprofen solution.
(c) Parallelly, the spectrophotometer was connected to the software and cuvettes and
waste beakers were laid out.
(d) The magnetic stirring stick was dropped slowly, and the knob turned to begin stirring.
A record of the solution's initial pH was made.
(e) To lower the pH, drops of HCl were added methodically using the 1cm3 dropper.
(f) The absorbance values were recorded using the spectrophotometer by transferring
drops of the solution to a cuvette.
(g) Steps (e) and (f) were repeated for all the values of pH (2, 4, 6, 8, 10).
(h) The HCl was allowed to sit with the Ibuprofen for 10 minutes before recording the
absorbance values. After the use of the pH meter, it was rinsed with distilled water
and blotted dry.

Figure 4: Experimental Setup Figure 5: Crushed Ibuprofen Tablets

Safety, Ethical and Environmental Concerns

1. Skin Protection: Throughout the extraction and spectrophotometry, nitrile rubber

chemical-resistant gloves were worn. After a single use, the latex gloves were
properly disposed away, and water and soap were used to wash the hands.
2. Proper Apparatus Usage: All the solvents and liquids were kept separate from the
Spectrophotometer to avoid damage to the appliance.
3. Proper disposal: Chemicals and solvents used were carefully discarded in a waste
tank to refrain from contamination and contact with unsafe substances.
4. Usage of 1M Hydrochloric acid: The handling of HCl was done with caution
because it can result in serious skin burns and eye damage if introduced to the skin.

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 HL Chemistry Internal Assessment Candidate Number: XXXXXX-0001
Examination Session: May 2023 Candidate Code: jtj551
Protective gloves and goggles were worn, and hands were washed thoroughly after
usage.
5. Proper Ventilation: The HCl solution was kept sealed while it was not used and
stored in a fume hood to avoid breathing the fumes as it is toxic to the human body.
6. Proper electrical appliance usage: All electrical appliances like the blender and
spectrophotometer were used safely and plugged in appropriately.
7. Usage of 1M Sodium Hydroxide: Due to the risk of strong interactions with alkali
metals, protective gloves were worn while using it and hands were thoroughly washed
after use. It was labelled clearly and stored in a safe place.
8. Usage of Ibuprofen: Due to the risk of eye and respiratory irritation, protective
gloves were worn to protect the face and hands. It was used in a well-ventilated area
to avoid an accumulation of dust.
9. Preventing Wastage: Ibuprofen is an important analgesic, which is why only the
needed amount was used for this experiment to reduce any wastage.

No ethical concerns were observed.

Qualitative Observations

While preparing the stock solution, slight fizzing was observed when the Ibuprofen powder
was added to the NaOH. This progressed to slight bubbling when the solution was mixed in
the volumetric flask. No colour change was observed after the addition of HCl or during the
varying pH values.

Quantitative Data

Table 3: Showing the effect of pH (2, 4, 6, 8 and 10) on the absorbance values of Ibuprofen
with the mean and standard deviation.

Absorbance (AU) 0.001

Raw Data Processed Data

pH 0.2 units Trial 1 Trial 2 Trial 3 Trial 4 Trial 5 Mean Standard Deviation

2.0 0.131 0.133 0.130 0.130 0.133 0.1314 0.0015

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4.0 0.096 0.097 0.097 0.096 0.097 0.0966 0.0005

6.0 0.087 0.085 0.085 0.086 0.087 0.0860 0.0010

8.0 0.082 0.082 0.080 0.082 0.082 0.0816 0.0009

10.0 0.067 0.067 0.066 0.069 0.068 0.0674 0.0011

Table 4: Shows the processed data for change in absorbance values (AU) of Ibuprofen at all
pH values (2, 4, 6, 8 and 10) indicating the rate of degradation.

Processed Data
Change in
pH  0.2 units A0 (initial) At (final) absorbance (A0-At) Rate of Degradation (%)

2.0 0.731 0.1314 0.5996 82.02

4.0 0.731 0.0966 0.6344 86.79

6.0 0.731 0.0860 0.6450 88.24

8.0 0.731 0.0816 0.6494 88.84

10.0 0.731 0.0674 0.6636 90.78

Sample Calculations

Table 5: Showing the sample calculations for pH 2.

Formula Calculation

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Mean
0.131+0.133+0.130+ 0.130+0.133
5

¿ 0.1314 AU

Degradation Rate
0.731−0.1314
×100
0.731

¿ 82.02 %

Standard Deviation

√ ( 0.131−0.1314 )2+ …+ ( 0.133−0.1314 )2

5−1

¿ 0.0015 AU

Table 6: Showing the absolute and percentage uncertainties of the apparatus used
Apparatus Absolute Uncertainty Percentage Uncertainty
UV Vis Spectrophotometer  0.001 AU 0.001
× 100=1.51 %
(smallest reading is taken as 0.066
0.066 AU)
pH meter and Probe  0.2 pH units 0.2
×100=10.00 %
(smallest reading is taken as 2
2)
100 mL volumetric flask  0.08 mL 0.08
× 100=0.40 %
(smallest reading is taken as 20
20 mL)
Electronic weighing scale  0.005g 0.005
× 100=5.00 %
(smallest reading is taken as 0.1
0.1g)
Total Percentage Uncertainty 16.91%

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HL Chemistry Internal Assessment Candidate Number: XXXXXX-0001
Examination Session: May 2023 Candidate Code: jtj551

Effect of pH on Degradation Rate of Ibuprofen

92
90 f(x) = 5.10814563770005 ln(x) + 78.9022622410552
Degradation Rate (%)

88 R² = 0.969076494400562
86
84
82
80
78
76
1 2 3 4 5 6 7 8 9 10 11

pH
Series2
Degradation Rate (%)
Logarithmic (Degradation Rate (%))
Graph 1:
Trendline showing the degradation rate (%) of Ibuprofen for increasing pH values.

Analysis and Interpretation

As the pH increases, the change in absorbance (AU) increases, accelerating the degradation
rate of ibuprofen (%), according to the results presented in tables 3, 4, and graph 1. The graph
displays a significant positive correlation that supports the theory and the relationship. An
increase in the pH from 2 to 12 showed that the rate increased from 82.02% to 90.78%. It
must be noted that the similarity in rates of degradation of pH 6 (88.24%) and pH 8 (88.84%)
may indicate its degree of stability around those pH values. This is further substantiated by
the sharp increase in the rate of degradation from 88.84% to 90.78%, showing a degree of
instability.

Regression Analysis
The logarithmic regression coefficient (R2) value is 0.9691, as can be seen from the graph.
Since this number is more than 90% of the R2 value scale, it is evident that the graph exhibits
strong positively correlated values. According to the change in absorbance readings (AU),
there is a significant correlation between the pH of Ibuprofen and the degradation rate(%).

Standard Deviation and Error Bars

The standard deviation shown is very small at varying pH values with the highest being only
0.0015. This shows that the absorbance values for a particular pH value fluctuate very little.
Conclusions can be made based on the data, which can be deemed accurate. It must be noted
that the magnitude of the uncertainty is quite high and can influence the absorbance values
collected and hence the degradation rates calculated. However, it does not disprove the
hypothesis as the trend remains the same. Hence it does not obscure the conclusion of this
investigation and can be reduced by using apparatus with less instrumental uncertainty.

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Conclusion
This investigation is supported by the research (Iovino et al., 2016a), that Ibuprofen
degradation increases with an increase in the pH. This is reflected in the strong correlation in
this paper supporting the hypothesis that as the pH increases, the change in absorbance (AU)
increases thereby increasing the degradation rate (%) of Ibuprofen.

Evaluation
Strengths:

1. A total of 25 data points were generated by taking five samples of five different
concentrations. This gives us enough information to draw a cogent and concise
conclusion
2. A Preliminary trial was conducted to test the variables before the actual investigation,
improving the accuracy and reducing error.
3. The solution with Ibuprofen and HCl was constantly stirred using a magnetic stirrer
while experimenting to ensure all pH is constantly maintained, resulting in an
accurate experiment.

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HL Chemistry Internal Assessment Candidate Number: XXXXXX-0001
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Table 7: Evaluation of the errors in this experiment
Type and Source of error Possible effect on Suggested Improvement
measured data and
magnitude of error
Systematic Error: The The absorbance values Capsules should be
Ibuprofen tablets were could be affected as it looked for instead which
coated and impure. was not 100% pure can be dismantled, and
Ibuprofen as they were drug taken out in its pure
coated with sugar or film. form.
The HCl may react with
the impurities and not just
the drug, increasing the
magnitude of error.
Systematic error: the There could be slight New batches should be
Ibuprofen stock solution degradation by light and made regularly for every
was kept for a long period temperature due to it trial.
of time during the being in storage for long,
investigation increasing the magnitude
of error and increasing the
degradation rate.
Systematic error: the This could affect the Calibration should be
uncertainty of the pH calibration of the pH done more accurately to
meter and variability of meter and hence the reduce this error.
pH buffers should be recording of pH values.
accounted for.
Independent Variable: the A higher rate of A wider range could have
pH values were from the degradation could have been taken if not for the 5
entire range and stopped been shown at pH values trials.
at 10. >10
Random Error: A few If the sample spills, the To improve precision and
drops of the sample may concentration will decrease inaccuracy,
have spilt while being change, altering the repeat the experiment.
transferred from test tubes amount of ibuprofen,
to glass cuvettes. which can raise the
degree of mistake.
Random Error: A possible As some crushed To improve precision and
error in crushing the Ibuprofen would be left decrease inaccuracy,
tablets and transferring it behind in the mortar and repeat the experiment.
from the mortar and pestle pestle, less Ibuprofen
to the container. would be taken for the
investigation, increasing
the magnitude of error.
Random Error: Changes Fluctuations in electric To improve precision and
in the power supply of the devices can lead to decrease inaccuracy,
electronic balance. fluctuations in the repeat the experiment.
measured value
increasing the magnitude
of error.

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HL Chemistry Internal Assessment Candidate Number: XXXXXX-0001
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Proposed Extensions

The stability of Ibuprofen can be studied by varying factors like temperature and UV light as
well which can provide more discussion on this drug’s use and mechanism in our body. More
variables can be used with pH which would increase the scope of this exploration and provide
more data points to conclude. Lastly, A similar analgesic can be taken and studied by varying
the pH to compare the results with those of this investigation as well.

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