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“Study of the influence different types of organic solvents might have over the yielding of ibuprofen purification from commercial
tablets; and its purity determined by means of thin layer chromatography.”
Carlota Alonso 1
EXTENDED ESSAY
CHEMISTRY
Study of the influence of the polarity index of
organic solvents over the yielding of ibuprofen
purification from commercial tablets, and its
purity, determined by means of thin layer
chromatography.
Author: Carlota Alonso Pardal
Candidate number: 001787002
Date: 01-03-2011
Word count: 3942
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 2
ABSTRACT
There are several situations in which ibuprofen recycling would undoubtedly
pose a beneficial outcome: tablets may fail to meet the manufacturing requirements,
they could go off date once on the market, its incorrect disposal could threaten the
environment... Nonetheless, this would have to be feasible and economically profitable
in order to be carried out. This is why I want to study whether the polarity index of the
solvents used for the isolation of ibuprofen from commercial tablets play a determining
role in the yield obtained, not only as a matter of quantity, but also considering its
purity.
Five different solvents, with polarity indexes ranging from 0 to 5, where used for
the extraction of ibuprofen, which involved dissolving the grinded commercial tablets in
such solvent, then filtering the solutions and finally evaporating the liquid. The purity of
the extract was next assessed by means of TLC.
My results suggest the difference in the polarity index of the solvent used does
not influence the yield of ibuprofen isolated, which ranges an 85% recovery. However, a
difference can be appreciated in the case of trichloromethane, where the extraction yield
is higher than 100%. Besides, there is no apparent correlation between the polarity
index and its effect over the purity of the sample.
It can also be highlighted that the low cost of the solvents significantly reduce the
budget of this procedure. Furthermore, the stripped solvents where condensed and
collected; this recycling also reduces the cost, as the solvents are not totally consumed,
but a large volume of the original solvents was back in its original state by the end of the
experiment.
Word count: 270.
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 3
INDEX
ABSTRACT ........................................................................................................................................... 2
INDEX .................................................................................................................................................... 3
1. INTRODUCTION ........................................................................................................................ 4
2. MATERIALS AND METHOD.................................................................................................... 7
a. Instruments ......................................................................................................................................... 7
b. Reactants .............................................................................................................................................. 7
c. Method ................................................................................................................................................... 8
i. Ibuprofen extraction: .................................................................................................................................. 8
ii. TLC analysis: ................................................................................................................................................... 9
3. RESULTS ................................................................................................................................... 10
a. Ibuprofen extraction ..................................................................................................................... 10
b. TLC analysis ...................................................................................................................................... 13
4. DISCUSSION ............................................................................................................................. 15
a. Conclusion ......................................................................................................................................... 15
b. Evaluation of procedures ............................................................................................................. 16
i. Strengths........................................................................................................................................................ 16
ii. Limitations .................................................................................................................................................... 17
iii. Sources of error and possible improvements ................................................................................ 18
iv. Reliability of my data ................................................................................................................................ 19
ACKNOWLEDGEMENTS ................................................................................................................ 19
BIBLIOGRAPHY ............................................................................................................................... 21
BACKGROUND READING ............................................................................................................. 23
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 4
1. INTRODUCTION
When a company develops new drugs, it is frequent they get hold of a patent, a
legal monopoly, which gives such company only the right to sell this drug for a period of
twenty years, starting from the date of the register. Once it expires, however, other
companies are free to sell the same drug too; thus competence rises among them as they
are all now commercializing a product defined as “generic drug”, sold with the name of
the active ingredient instead of the original brand name.
A good example occurred in 1984, when the patent for ibuprofen from the
chemical company Upjohn expired [1]. Ibuprofen is a non-steroidal drug derived from
propanoic acid, which chemical name is 2-(4-isobuthylphenyl) propanoic acid. It has
analgesic, anti-inflammatory and antipyretic properties as a consequence of its capacity
to inhibit prostaglandin sintetase. After patent expiring, companies immediately began
to participate in a competitive race in which everyone hankered after obtaining the
greater economical benefits, even if that meant reducing the consumer cost to rise
selling figures. The original selling company, Upjohn, felt obliged to reduce the price of
their product, Motrin, by 35% to be able to compete with the new tablets, containing the
same active ingredient, now being sold in the market. The consumer price was later on
reduced by two thirds of the original cost.
This is one example of the importance for a company of optimizing their
processes. However, no single chemical process can assure a pure yield at all times. Due
to reasons that at times might be unavoidable, tablets may fail to meet the
manufacturing, health or security requirements, thus not to be sold or used at any case,
raising both the company economical cost and the consumer one. Nonetheless, if these
active ingredients could somehow be recycled, whilst meeting the safety standards,
obtaining a high yield, and resulting in an overall economically profitable process, the
above-stated consequences could possibly be avoided.
Ibuprofen is widely used among society, and its manufacture is just as broad. It
requires some specific storage conditions [2], which though might not be very strict
(kept in its original container, at room temperature and avoiding humid environment),
do have to be followed. Otherwise, the drug could lose its properties; or even pose
serious harm effects if consumed. In addition, “current-day pharmaceutical formulation
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 5
may be trial and error in nature (…).”1, which means during the manufacture process,
drug industries could come across considerable losses.
It could also occur the tablets went off date, being therefore not useful any longer.
If these were merely thrown away, not only would we be wasting natural resources;
also, we would be to blame of a detrimental outcome over the environment. An
investigation published by CSIC2 in the year 2005 [3] verified the presence of PhACs3 in
the waters of river Ebro. This poses harsh consequences over the surroundings, as these
drugs bring about high risks of contamination, threatening the species living in such
ecosystems. Investigators work on the recovery of those spilled drugs, among which
ibuprofen represents a considerable fraction of the total. To diminish our footprints and
increase the sustainability of the chemical industry, the recovery and recycling of
ibuprofen would connote a fair solution.
Figure 1: three-dimensional structure of ibuprofen4
1 Bushra, Rabia, Muhammad H. Shoaib, Nousheen Aslam, Durriya Hashmat, and Masud Ur-Rehman. "Umm
Al-Qura University." Formulation development and optimization of ibuprofen tablets by direct compresision
method. Department of Pharmaceutics, Faculty of Pharmacy, University of Karachi, Karachi-7520,
Pakistan. Ministry of Health, Government of Pakistan, n.d. Web. 3 June 2010.
<uqu.edu.sa/files2/tiny_mce/plugins/filemanager/files/4290454/Paper-6.pdf>.
2 Centro Superior de Investigaciones Científicas
3 Pharmaceutically Active Compounds
4 Harrison, Karl. "Chemistry, structures and 3D molecules." Top 50 prescription medicines. N.p., n.d. Web.
17 Apr. 2010. <www.3dchem.com/imagesofmolecules/ibuprofen.jpg>.
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 6
Figure 2: Structural formula of ibuprofen5
These are the main grounds why I want to focus my extended essay on recovery
of ibuprofen. There is also a personal interest to this investigation. Drugs are an
essential part to every medical speciality, particularly one as widely used as ibuprofen is.
I want to become a doctor myself and I have a strong awareness over some medical
aspects. The use of drugs in special is one of my main concerns, not only because of its
possible effects, but also because of the economic and environmental implications. Thus
I think it is fundamental to dedicate strong emphasis on determining whether it is
feasible and profitable to recycle over-the-counter drugs, and how it is best to do so.
To carry out this study, I have done some research, both on the Internet and at
the library that has enabled me to design a method for my study, by comparing several
published methods followed for similar purposes, and create an adequate one focusing
on my specific needs. At the end, I decided to check if the polarity of the solvent should
influence the yield of recovery of ibuprofen, remembering the well known rule “similar
dissolves similar”, and so I selected a range of different solvents with different polarities
5 "Google Image Result for http://www.3dchem.com/imagesofmolecules/ibuprofen.jpg." Google. N.p., n.d.
Web. 9 Jan. 2011.
<http://www.google.es/imgres?imgurl=http://www.3dchem.com/imagesofmolecules/ibuprofen.gif&img
refurl=http://www.3dchem.com/molecules.asp%3FID%3D14&usg=__v-
zpKn2qO_q66W2Kk6075m_t5nU=&h=190&w=166&sz=3&hl=es&start=51&sig2=Cc4PU7cgkhGNXrYTTM
yDQw&zoom=1&tbnid=c6BI-
sT77RwTvM:&tbnh=140&tbnw=120&ei=EuZsTcmjHMT_lgei0r3qBA&prev=/images%3Fq%3Dibuprofen
%26um%3D1%26hl%3Des%26sa%3DN%26biw%3D1209%26bih%3D602%26tbs%3Disch:10%2C146
2&um=1&itbs=1&iact=hc&vpx=830&vpy=130&dur=5443&hovh=152&hovw=132&tx=76&ty=114&oei=n
-RsTdzKPIOB8gaDsrmODQ&page=4&ndsp=18&ved=1t:429,r:4,s:51&biw=1209&bih=602>
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 7
to study whether the polarity index of the solvent being used in the extraction process of
ibuprofen could play a determining role over the yield obtained, checking the purity of
the extracts by TLC. The final title of my research is: “Study of the influence of the polarity
index of organic solvents over the yielding of ibuprofen purification from commercial
tablets, and its purity determined by means of thin layer chromatography.”
2. MATERIALS AND METHOD
a. Instruments
� Stirring plates
� 250 mL Erlenmeyer flasks
� Magnets
� Spatula
� Mortar
� Funnel
� 50 mL beakers
� 10 mL pipettes ± 0,05
� Water vacuum pump
� Electrical heater
� Distillation equipment
� Oven
� Scale (OHAUS SCOUT PRO, ± 0,01 g)
� Filtering crucible
� Pasteur pipettes
� Scissors
� Pencil
� Ruler
� UV sensible silica TLC plates
� 254 nm UV lamp
b. Reactants
• Ibuprofen: MYLAN EFG Comp. recub. 600 mg. White, capsule-shaped,
coated tablets, containing 600 mg ibuprofen each [4].
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 8
o Excipients:
� Microcrystalline cellulose
� Cornstarch
� Sodium starch glycol
� Magnesium stearate
� Talc
� Colloidal anhydrous silica
� Povidone
o Coating:
� Hypromellose
� Titanium dioxide
� Glycerol triacetate
• Organic solvents [5-9]:
o Hexane: PANREAC6
o Methylbenzene: PANREAC
o Dichloromethane: PANREAC7
o Trichloromethane: PANREAC8
o Propanone: PANREAC
c. Method
After reading several methods [10-15] for analogous aims and considering some
general factors, such as the expected productivity, operating conditions, environmental
issues and material availability, I designed the following procedure, which consists
mainly of two steps:
i. Ibuprofen extraction
The already washed, to-be-used, glassware was rinsed with propanone to remove
any possible remains of water. Using a mortar, two tablets, containing exactly 1,20 g of
pure ibuprofen, were grinded thoroughly. This powder was then placed in an
6 “Hexane, mixture of alkanes, C6H14: Mixture of hidrocarbons, composed mainly of: 50% of n-Hexane, 45%
of isomers (2- y 3-Methylpentanes and Methylciclopentane) and variable quantities of Dimethylbutanes
and Ciclohexane.“
7 “Stabilized with X20 ppm of amylene (PAR) PAI”
8 “Stabilized with etanol (PAR) PAI”
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 9
Erlenmeyer flask, where 15 mL of the desired solvent were also added. A magnet was
finally put into the flask, which was placed on a stirring plate.
After exactly 20 minutes the flask was removed from the stirring plate and its
content was poured through a filtering crucible with the help of a water vacuum pump.
Once filtered, the solvent from the sample was evaporated, condensed and collected,
using a conventional distillation equipment. The sample was removed from the heating
source when, although most of the solvent had evaporated, still a small amount of it
could be appreciated, to make sure the samples were not overheated. The remaining
solid was let to evaporate at room temperature.
When the sample was considered to be dry, it was weighed. Immediately
afterwards, it was placed inside an oven at 70 ºC for 24 hours just to ensure any possible
traces of solvent would indeed disappear. Then a second reading of the weight of the
sample was taken.
This process was repeated three times for each of the five solvents.
ii. TLC analysis
To assess the purity of the different ibuprofen extractions, the samples were
analyzed by means of TLC.
The eluting solvent, 1% glacial acetic acid in ethyl acetate, was prepared, as well
as a 50/50 solution of ethanol/ethyl acetate. 3 mL of this latter solution were poured
into six test tubes. Each of them was assigned to a solvent, and a small amount of the
first extraction of such solvent was added. In the sixth test-tube, a small amount of
grinded commercial tablet was added. Within a couple minutes the solids would
dissolve.
A horizontal line at about 1,5 cm from the bottom end of the two TLC plates that
were going to be used was traced, and points were pencil-marked. The samples were
spotted in the plate three times (the ones corresponding to hexane, methylbenzene and
dichloromethane were spotted on the first plate, whilst trichloromethane, propanone
and the commercial tablet were spotted on the second plate).
The plates were introduced into two separate development chambers, containing
the eluting solution. Once finished, the length travelled by the solvent was marked with
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 10
pencil, and the plates were let to dry. Finally, they were observed under a UV light that
enabled to mark each spot. The Rf factors for each spot could then be calculated.
This process was repeated for the second and third trial of every solvent.
3. RESULTS
a. Ibuprofen extraction
Table 1 comprises the properties for every solvent used [16-19], considered
relevant for the aim of this investigation. The boiling point for each solvent is included
because of the need of heating the filtrate so that the solvent evaporates. Note the
increasing values of the Snyder polarity index (P’) for the selected solvents. This
parameter is a measure of the ability of the solvent to interact with various polar test
solutes [19]. Compare the values from the table with the one from water, i. e., 10,2.
Table 1: Solvent Properties
Solvent Boiling
point (ºC)
Density
(g/mL)
Polarity
index (P´)
Solubility in
water (%)
Hexane 68 0,65 0 0,001
Methylbenzene 110 0,86 2,4 0,05
Dichloromethane 39 1,3 3,1 1,6
Trichloromethane 61 1,4 4,1 0,81
Propanone 56 0,78 5,1 100
Table 2 presents the results acquired from the extraction of ibuprofen. Its
purpose is essentially to illustrate the relationship between the polarity index of the
solvent used and the mean percentage yield. We can notice that trichloromethane is the
only solvent that shows a mean percentage yield over 100%, unmistakable indicative of
error, whereas the rest of the solvents show values between 80% and 91%. The highest
value for the standard deviation is ±10%.
I have to mention that the qualitative results may also give us a hint to explain the
obtained data. Whereas the extraction of ibuprofen from hexane, methylbenzene,
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 11
dichloromethane and propanone resulted in a plain, white, crystalline solid powder, the
extract from trichloromethane had a slightly yellowish, heterogeneous appearance. It is
also worth noting that the filtering of the former was considerably quick (no more than
five minutes); however, the latter would take up longer than 30 minutes in every of the
three cases, plus the samples being filtered showed, in the first case, an homogeneous
appearance (except for the insoluble matter), while in the case of trichloromethane
again there was solid showing a suspending behaviour, in all of the three trials.
It is important to highlight that in the case of every solvent, the results show to be
reproducible.
Table 2: Ibuprofen extraction
Solvent Hexane Methylbenzene Dichloromethane Trichloromethane Propanone
Polarity index 0,0 2,4 3,1 4,1 5,1
Trial number 1 2 3 1 2 3 1 2 3 1 2 3 1 2 3
Yield (g) ± 0,01 0,96 1,02 1,01 1,11 1,15 1,02 0,86 1,11 0,93 1,65 1,36 1,52 1,05 0,93 1,15
Percentage yield
(%) 80,0 85,0 84,1 92,5 95,8 85,0 71,6 92,5 77,5 137 113 126 87,5 77,5 95,8
Mean percentage
yield (%) 83 ± 2 91 ±5 80 ± 10 130 ± 10 86 ± 9
Graph 1 shows the percentage yield of ibuprofen extraction for every of the three
trials, corresponding to each of the five solvents. For every one solvent the results for
the trials are precise; to a certain extent, they present matching results under unvarying
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 12
conditions. Nonetheless, we can also tell that by comparing the five solvents altogether,
in spite of the results being reproducible, they do not seem to be accurate, seeing that
trichloromethane presents repeatable results as well, but within a higher percentage
value range.
Graph 2 represents the mean percentage yield obtained for each solvent. These
are positioned approximately between the values of 80% and 100% for hexane,
methylbenzene, dichloromethane and propanone, whilst the value for trichloromethane
is well over 120%. This suggests this solvent sets non-reliable results, as the yield being
obtained can never surpass 100%. Moreover, the representation of a best-fitting line
points towards a poor correlation between the results for each solvent, as for its polarity
index.
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 13
Graph 3 displays the mean percentage yield obtained for each solvent too, but
this time the results for trichloromethane have been removed. After plotting the best-
fitting line, we can notice how the linear regression denotes an inappreciable
correspondence between the polarity index of the solvent used and the mean
percentage yield obtained, being the function of such line almost constant.
b. TLC analysis
Figure 3: TLC plate number 1, under UV lamp Figure 4: TLC plate 1, as seen at normal conditions
Figures 3 and 4 show the TLC plate for the analysis of the extractions
corresponding to hexane, methylbenzene and dichloromethane, in this order, from left
to right. It can be seen that the spots are at a similar height of the plate, and this spot is
all we see- no other substances show to have developed.
Figures 5 and 6 show the TLC plate for the analysis of the extractions
corresponding to trichloromethane and propanone, and the grinded commercial tablet.
Once again, the spots are at the same height, and there is no other substance present. All
figures, 3, 4, 5 and 6, represent the analysis for the first trial of every solvent; the plates
for the other two trials showed to be identical.
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 14
Figure 5: TLC plate 2, under UV lamp Figure 6: TLC plate 2, as seen at normal conditions
Table 3 shows the Rf factors calculated from the spots on the TLC plates. Before
commenting on the results, it is worth noting that dissolution of samples took a few
minutes in all the cases, except again for trichloromethane. In addition, it presented an
oily, pale yellow aspect. Yet, the Rf factor shows to be alike for all six samples, including
trichloromethane.
Table 3: Extract purity analysis
Sample Polarity
index
Mean
yield (%)
Rf factor
Trial 1 Trial 2 Trial 3 Mean
Hexane 0,0 83±2 0,82 0,82 0,82 0,82
Methylbenzene 2,4 91±5 0,81 0,82 0,80 0,81
Dichloromethane 3,1 80±10 0,82 0,84 0,80 0,82
Trichloromethane 4,1 130±10 0,84 0,84 0,84 0,84
Propanone 5,1 86±9 0,83 0,81 0,85 0,83
Commercial
tablets 0,83 0,83 0,83 0,83
Mean 0,83 ±
0,01
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 15
Graph 4 represents the mean Rf factor calculated for each of the samples. Each
column is identified with a number that corresponds to a solvent, as shown on the key
above.
4. DISCUSSION
a. Conclusion
Considering the graphs above, we could conclude that, as far as my results
suggest, the difference in the polarity index of the organic solvents used does not have
an influence over the yield of ibuprofen isolated.
As we can deduce from table 2 and graphs 1, 2 and 3, the overall percentage yield
for hexane, methylbenzene, dichloromethane and propanone are regular (see Table 2
and Graph 2), coherent and consistent; they lie within a common range of values,
somewhere between 80% and 91%, independently of what their polarity index was. In
spite of this, we have rather unforeseen results for the samples corresponding to
trichloromethane which reveals extracts with a percentage yield of 125% in average,
being evident that some unpredicted, unexpected and/or uncontrolled situation at some
stage during the extraction process has headed to these misleading results.
However, the results from the TLC showed that all the five samples obtained
were pure. This adds to the conclusion that the polarity index of the solute used does not
have an effect over the purity of ibuprofen recovered.
Samples key:
1- hexane
2- methylbenzene
3- dichloromethane
4- trichloromethane
5- propanone
6- commercial
tablets
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 16
Nevertheless, not all the extract obtained in the case of trichloromethane can be
pure, as the maximum quantity would be that contained in the tablets, 1,20 g. When the
quantity recovered exceeds this number, it is clear not the entire sample is our desired
compound. But as we have seen that the TLC shown no insinuations of impurities
present, as all of the samples have practically the same Rf values, I can think of the
possibility that the impurities in the case of trichloromethane did not dissolve in the
50/50 solution of ethanol/ethyl acetate, but could have settled at the bottom. This
would explain that the fraction of the sample that did dissolve consisted only of pure
ibuprofen.
We also have to take into account that for the aim of this investigation only five
different solvents have been used, and their polarity index values only range from 0 to 5.
Maybe higher values might induce an effect. I strongly suggest this represents an
outstanding research question. In addition, as we unluckily found deceptive results for
one of the five solvents, I think we have insufficient data to support the trend that the
other four solvents suggest.
Obviously, if my results where taken as an indicator, and no further studies were
carried out, the economical implications would be impressive, because it would directly
mean that the process of ibuprofen recycling might not be profitable at all, or at least
could not be enhanced by the use of another solvent of known features.
But we do have to be aware of the limitations of my investigation. Not only do we
have to account for my budget limits, but also to the extension and requirements of my
work, which would unable me to produce a greater sample range, thus awarding more
reliability to my data.
b. Evaluation of procedures
i. Strengths
It can be highlighted that the low cost and availability within the school settings
of the solvents I chose to use significantly reduced the overall cost of this procedure. On
top of that, the stripped solvents where condensed and collected so as to give them
other uses in the future; this recycling also reduces the cost of the procedure, as the
solvents are not totally consumed, but a large volume of the original solvents was back
in its original state by the end of the experiment.
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 17
Besides, I decided to adapt the patent I consulted in several ways, and one of
them was carrying out this extraction at room temperature, meaning there was no
heating when the crushed ibuprofen tablets were dissolved in the corresponding
solvents. This was done intentionally in order to be able to fully control this parameter;
otherwise, our results could have shown as a function to the temperature being used as
well.
After filtering my samples, I placed them on a heating plate to distil the solvent. I
made sure they were not overheated by removing them from the plates when still a
small amount solvent was left, to let it dry at room temperature. Plus, I ensured I took
the exact weight of my dry samples by weighing them twice: once when I considered
them to be dry, and a second time after 24 hours in an oven at 70 ºC, which guaranteed
all the possible remaining solvent had evaporated. Readings showed consistent in every
case, which at the same time provides evidence of the strengths of my method.
Another important aspect is the quantities of reactants being used, which are
considerably larger in the patent in comparison with my procedure. In order to evaluate
the effect of the polarity index over the amount and purity of ibuprofen recovery I did
not consider necessary to use such large quantities of reactants, as whilst the solvents
could be easily recovered, the quantity of ibuprofen being used would significantly rise
the expense of the total procedure. Also, it is reasonable that within school conditions
and for safety reasons one cannot determine the ibuprofen recovered to meet the
required standards for consumption, nor we are able to safely transform it into
commercial tablets, so it would have to be thrown away.
With concern to the purity testing lead by the Thin Layer Chromatography
analysis, I also have to mention its low cost, whilst at the same time providing us with
reliable data and a rather fast analysis technique, which proves why it has become
fundamental for the determination of product purity among the drug industry.
ii. Limitations
The first step I had to take that could possibly be improved is the grinding
process, which can make happen substantial variations in the sample composition. As a
result of grinding, heat is evidently generated, that could be the means to the loss of
volatile components in my sample. Still, this would not have an effect on my results since
pure ibuprofen is not volatile, and the possibly volatile excipients, which might be lost
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 18
during the grinding process, would otherwise be removed after filtering. Relevant to this
grinding is also the potential contamination of my sample; then once again these
impurities are later on dealt with, and only the soluble matter -ibuprofen- will stay in
the filtered solvents.
However, I can also think of the possibility that, because of using only a small
amount of solvent in all the samples, perchance we did not enable the whole content of
ibuprofen in the tablets to dissolve. Nonetheless, the ratio of solvent to solute indicated
in the patent is well surpassed; therefore the only problem might be we did not provide
our solvents with the high temperature needed to allow for such dissolution, which
could maybe improve our percentage recovery at the end.
iii. Sources of error and possible improvements
The propagation error on my final results can be said to have two fundamental
components: random error and bias, related to precision and accuracy respectively;
however biases, or systematic errors, are unknown during the experimentation.
Nonetheless, both types of errors can probably be identified in my results.
I can deduce a systematic error being present in the extraction of ibuprofen in the
sample corresponding to trichloromethane. The fluctuations between the results for
each of the three trials, for every solvent, are arbitrary, most certainly produced because
of the small random fluctuations when grinding the solid and during the filtering step.
These act together producing slight disparities in the quantity being measured.
However, we can use two parameters to describe the differences in our results: these
are the mean and the variance (or the standard deviation in its place, which is merely
the positive square root for the value of the variance). Considering the other four
solvents, we can as well identify another systematic error, which implies the loss of a
15% of ibuprofen on average. This was most likely caused during the filtering step, and
could be highly diminished by washing the remaining solid in the filter with a small
extra amount of the same solvent used in each case, in order to dissolve possible traces
of ibuprofen retained in the non-soluble impurities simply by means of physical
adsorption between the molecules.
The first random error brought up, relating to the grinding of the solid, could
probably be reduced appreciably by increasing the number of measures being taken,
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 19
which was not viable within the requirements of this study, considering the limiting
length of about 40 hours.
Another possible improvement to this inquiry would be to study this same
question, now within values of polarity index close to the one corresponding to
trichloromethane, i.e. for values between 3,5 and 4,5. Some possibilities would be 1,2-
dichloroethane, butyl acetate, 2-propanol, n-butanol, tetrahydrofuran, n-propanol or
ethyl acetate, with corresponding polarity indexes of (3,5), (3,9), (3,9), (4), (4), (4) and
(4,4) respectively.
iv. Reliability of my data
With regard to Chart 2, and Graphs 1, 2 and 3, we can safely state that the results
obtained prove to be reliable. In Graph 1 we can see how the values for every of the
three trials for each solvent are very close to each other, showing consistency. In Graph
2 we can observe that the average percentage yield for four out of the five solvents (this
is, hexane, methylbenzene, dichloromethane and propanone) are very similar. In
addition to this, I have to point out that the masses of the extract obtained for each
sample were measured twice, before and after being placed inside the oven to make sure
they were completely dry and we would be considering the pure sample only. The
outcome was positive; the readings were identical in all the cases. This also insinuates
that there was something erroneous with trichloromethane, since in all the three trials it
showed a yield over 100%. This undoubtedly indicated that I was not measuring the
pure solvent only, so the samples were rejected (as can be seen in Graph 3) because they
would mislead possible conclusions. Yet, I am not aware the cause or origin of this
impurity; I assume during the stirring of ibuprofen with the solvent some side reaction
must have occurred, resulting in the production of another compound, which had to be
also soluble in that given solvent. This would explain why this unknown substance
would have gone through the filtering crucible along with the desired pure ibuprofen.
Anyhow, it resulted in unreliable results.
ACKNOWLEDGEMENTS
It is a pleasure to thank those who made this Extended Essay possible:
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 20
I owe my deepest gratitude to my supervisor, D. Víctor, for his guidance, his
sound advice and his patience at all times.
I am extremely thankful to Dra. Moya for allowing me to use the equipment in her
department at University.
I am grateful to D. Luis as well, for urging me to bring this project to an end, and
for making available his support in all possible ways.
And thank you, must I say, to my family, for being always my biggest source of
encouragement.
“Study of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial tablets,
and its purity determined by means of thin layer chromatography.”
Carlota Alonso Pardal 21
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BACKGROUND READING
• Atkins, P. W., and Jo A. Beran. General chemistry . 2nd ed. New York: Scientific
American Books
• Atkins, Peter William, and Loretta L. Jones. Chemical principles: the quest for
insight. 4. ed. New York: W.H. Freeman, 20082007.
• McMurry, John. Fundamentals of organic chemistry . 3rd ed. Pacific Grove, Calif.:
Brooks/Cole Pub. Co., 1994.
• Morrison, Robert T., and Robert N. Boyd. Organic chemistry . 6. ed. Englewood
Cliffs, N.J: Prentice Hall, 1992.
• Solomons, T. W. Graham, and Craig B. Fryhle. Organic chemistry . 9th ed. Hoboken,
NJ: John Wiley, 2008.
• Zumdahl, S. S.. Chemical principles . 6. ed. Boston: Houghton Mifflin, 2009-2008.