PPM20403 Pharmaceutical Analysis

ACID-BASE TITRATION

Experiment No. 1

Introduction

In a titration, a burette is used to dispense measured increments of one solution into

a known volume of another solution. The object of the titration is the detection of the
equivalence point, that point in the procedure where chemically equivalent amounts
of the reactants have been mixed. Whether or not the equivalence point comes when
equimolar amounts of reactants have been mixed depends on the stoichiometry of
the reaction. In the reaction of HCl and NaOH, the equivalence point does occur
when one mole of HCl has reacted with one mole of NaOH. However, the reaction of
H2SO4 and NaOH, the equivalence point occurs when two moles of NaOH have
reacted with one mole H2SO4. The titration technique can be applied to many types
of reactions, including oxidation reduction, precipitation, complexation, and acid-base
neutralization reactions.

Although a variety of instrumental methods for detecting equivalence points are now
available, it is frequently more convenient to add an indicator to the reaction mixture.
An indicator is a substance that undergoes a distinct colour change at or near the
equivalence point. The point in the titration at which the colour change occurs is
called the end point. Obviously, the titration will be accurate only if the end point and
the equivalence point coincide fairly closely. For this reason, the indicator used in a
titration must be selected carefully. Fortunately, a large number of indicators are
commercially available and finding the right one for a particularly titration is not a
difficult task.

Procedure:

A. Standardization of NaOH

1. Rinse a burette twice with small portions of the NaOH solution provided.
Finally, fill the burette with this solution.
2. Accurately weigh, to the nearest tenth of milligram, 0.4 to 0.6 gram of the
oxalic acid dehydrate and add it to a 125 mL Erlenmeyer flask.
3. Add 25 mL of distilled water and 2 to 3 drops of phenolphthalein indicator
solution. Swirl to dissolve the solid.
4. Read the initial volume of NaOH solution in the burette to the nearest
hundredth of millilitre.
 5. Titrate the oxalic acid dehydrate solution with the NaOH solution until a faint
pink colour, which does not disappear when the solution is mixed, is obtained.
6. Read the final volume of NaOH solution in the burette to the nearest
hundredth of a millilitre.
7. Calculate the molarity of the NaOH solution.
8. Repeat the standardization in triplicate and average the results.

B. Analysis of Ibuprofen

Ibuprofen is an organic compound (its chemical name is (RS)-2-[4-(2-methylpropyl)

phenyl] propionic acid) widely used as nonsteroidal anti-inflammatory drug applied in
fever, arthritis, and as pain reliever. Ibuprofen is known to have an antiplatelet effect,
though it is relatively mild and somewhat short-lived when compared with aspirin. Its
analgesic (pain relieving) action starts after 30 min and lasts few hours. Ibuprofen is
removed with urine and does not cumulate in human body. Numerous drugs contain
this compound, the most popular are Ibum, Ibufen, Ibumax, Ibuprofen, Ibuprom,
MIG, Nurofen, Modafen etc.

In our exercise students will analyze tablets of commercial drugs containing

Ibuprofen and calculate the content of the active component C12H17COOH. Tablets
usually contain different neutral components, like starch, which however do not
obscure the endpoint. Ibuprofen has one ionizable hydrogen (one-carboxylic acid)
and the dissociation constant is pKa1=4.40 [1]. This makes its acid-base titration
relatively simple, not very different from that of, say, acetic acid (pKa=4.8).
As seen from the theoretical titration curve, the proper indicator in this experiment
will be Phenylphthalein, which becomes red starting at ca. pH=8.3. The only problem
can be very low solubility of Ibuprofen in water (21 mg/L at 25C). On the other hand,
this compound is well soluble in alcohols, including the polyhydroxyl ones (for
example glycerol, HO-CH2-CH(OH)-CH2-OH), and we will exploit this fact in our
procedure. However, commercial glycerol usually contains traces of acids and this
could influence the result, so it should be neutralized prior to titration.

Procedure

1. Pour ca. 50 mL of glycerol and ca. 50 mL of hot water to Erlenmayer flask and
heat it to ca. 60⁰C (the liquid is hot but does not burn).

2. Add 2-3 drops of Phenylphthalein and add slowly, drop by drop, your titrant
NaOH solution, stirring the content vigorously until rose colour appears. Add
titrant solution to the burette up to initial mark or note the actual level of it.

3. Place the tablet in the flask, crush it with your glass stirring rod. Add additional
1-2 drops of indicator and titrate the content until red colour appears.

Make two independent titrations at least. Calculations As seen from the theoretical
titration curve, Ibuprofen behaves in this experiment like typical monoprotic acid.
Thus, the number of moles of NaOH added at the end point of titration should be
directly equal to that of Ibuprofen in the tablet. Calculate the mass of the acid,
independent for these two titrations and their arithmetic mean. Compare the obtained
result with that claimed by drug producer (usually 200-400 mg, this number will be
obtained from your teacher after completing the experiments). Remember that this is
quantitative analysis and all the numbers during measurements and calculations
should be noted in proper number of significant digits. The molecular mass of
Ibuprofen is equal to 206.28 g/mol.
M. Meloun, S. Bordovska, L. Galla, Journal of Pharmaceutical and Biomedical Analysis 45 (2007) 552–564