Study of the influence of the polarity index of organic ...€œStudy of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial

“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.




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




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




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>.




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>




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].




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”




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




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,




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




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.




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.




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




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




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.




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




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,




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:




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.




BIBLIOGRAPHY

1. Krugman, Paul R., and Robin Wells. "Microeconomía - Google Books." Google

Libros. N.p., n.d. Web. 10 Dec. 2010.

<http://books.google.es/books?id=ld8I68bW3eoC&pg=PA209&lpg=PA209&dq=c

oste+del+ibuprofeno&source=bl&ots=Br1HWJ4m22&sig=vnX9FSbZUTcgvMo0FP

RP-

wWoFls&hl=en&ei=ZFVUTdegJpLf4gbW84ikCQ&sa=X&oi=book_result&ct=result&

resnum=5&ved=0CDYQ6AEwBA#v=onepage&q=coste%20del>.

2. "PubMed Health - Ibuprofen." National Center for Biotechnology Information. N.p.,

n.d. Web. 10 Jan. 2010.

<http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000598#a682159-

otherUses>.

3. "Los fármacos también pueden contaminar, recíclalos - repsol.com." Repsol - Repsol

YPF - repsolypf - repsolypf.com . N.p., n.d. Web. 10 Jan. 2010.

<http://www.repsol.com/es_es/energia-casa/conciencia-

sostenible/reportajes/farmacos_contaminan.aspx>.

4. "IBUPROFENO MYLAN EFG - Composición cualitativa y cuantitativa."

Vademecum.es - Información: de Medicamentos y Principios Activos - Noticias,

Diccionario. N.p., n.d. Web. 9 Jan. 2010.

<http://www.vademecum.es/medicamento-

ibuprofeno+mylan+efg_composicion_27172_2>.

5. “Safety Information Sheet. PANREAC, Analytical Reagents and Fine Chemicals."

N.p., n.d. Web. 22 Apr. 2010.

<www.panreac.es/english/catalogo/fichastec/131745IN.HTM>.


N.p., n.d. Web. 22 Apr. 2010.

<http://www.panreac.es/english/catalogo/fichastec/131745IN.HTM>.


N.p., n.d. Web. 22 Apr. 2010.

<http://www.panreac.es/spanish/fds/ING/X321254.htm>.





N.p., n.d. Web. 22 Apr. 2010.

<http://www.panreac.es/spanish/fds/ING/X321252.htm>.


N.p., n.d. Web. 22 Apr. 2010.

<http://www.panreac.es/spanish/catalogo/fichastec/481007ES.HTM>.

10. "Isolation of ibuprofen from tablets - Patent 5300301." Patent Searching and

Inventing Resources. N.p., n.d. Web. 10 Feb. 2010.

<http://www.freepatentsonline.com/5300301.html>.

11. "TLC chromatographic-densitometric assay of ibuprof... [J Chromatogr Sci. 2010] -

PubMed result." National Center for Biotechnology Information. N.p., n.d. Web. 19

Feb. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/21044413>.

12. "Dichloromethane Physical Properties chart by Sigma-Aldrich.." Sigma-Aldrich:

Analytical, Biology, Chemistry & Materials Science products and services.. N.p., n.d.

Web. 10 Feb. 2010.

<http://www.sigmaaldrich.com/chemistry/solvents/dichloromethane-

center/physical-properties.html>.

13. "Hexane Solvent Properties." Louisiana State University Macromolecular Studies

Group. N.p., n.d. Web. 10 Feb. 2010.

<http://macro.lsu.edu/howto/solvents/hexane.htm>.

14. Swanson, Todd A. Ph.D. Chemistry, University of Minnesota. "Personal Websites,

Gustavus Adolphus College." . N.p., n.d. Web. 10 June 2010.

<homepages.gac.edu/~tswanso2/pdfs/chem101/Ident.of%20Drugs&Poisons.pdf

>.

15. "Chem 211 - Thin Layer Chromatography." Redirect to Wellesley College web site.

N.p., n.d. Web. 12 Feb. 2010.

<http://www.wellesley.edu/Chemistry/chem211lab/Orgo_Lab_Manual/Appendix

/Techniques/T

16. Murov, Steve. "orgsoltab." S. Murov home. N.p., n.d. Web. 19 Feb. 2010.

<http://murov.info/orgsolvents.htm>.

17. "Solubility of ibuprofen in organic solvents." Oral Roberts University - A Christian




College, based in Tulsa Oklahoma.. N.p., n.d. Web. 19 Feb. 2010.

<http://old.oru.edu/cccda/sl/solubility/allsolvents.php?solute=ibuprofen>.

18. "Solvent Polarity and Miscibility." Chemical Ecology - (c) 1996-2010 by John A.

Byers. N.p., n.d. Web. 10 Feb. 2010. <http://www.chemical-

ecology.net/java/solvents.htm>.

19. “Polarity Index." Louisiana State University Macromolecular Studies Group. Web. 01

Mar. 2011. <http://macro.lsu.edu/howto/solvents/Polarity%20index.htm>.

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.

Documents

Study of the influence of the polarity index of organic ...€œStudy of the influence of the polarity index of organic solvents over the yielding of ibuprofen purification from commercial