PHARMACEUTICAL ANALYSIS-1

FINAL ASSIGNMENT SPRING-2020

Submitted to, Submitted by,

Dr. NUSRAT SHUBHAN SUMAIYA ZAMAN PROME

ASSISTANT PROFESSOR ID: 1822001649

NORTH SOUTH UNIVERSITY. COURSE:224.1
SECTION: 01

JUNE 10, 2020

DEPARTMENT OF PHARMACEUTICAL SCIENCES
 Titrimetric

Introduction:

Titration is a method of quantitative chemical analysis that is used in the laboratory to determine
the unknown concentration of an identified analyte. The titrant is a solution of known
concentration and the unknown substance called ‘Titrand’. As titration is used to measure the
volume, it is also known as volumetric analysis.

Description: [2]

Acid and base can be described by three famous theory. For acid and base, one of the prominent
theory is given by the Swedish scientist Svante Arrhenius, that acids are substances that
dissociate in water and give a positively charged ions (H +), and that bases ionize in water and
give negative ions (OH −). Dissociation is defendant on the solvent. Another scientist named J.N.
Bronsted and J.M. Lowry independently proposed a broader theory of acid and bases. In an acid-
base reaction, acid gives a proton and convert into the conjugated base and vice-versa. According
to conjugated theory, in an acid-base reaction, the acid (HA) gives up its proton (H+) to produce
a conjugate base of the original acid and vice-versa. There are 4 types of acid-base titration. The
strong acid-strong base where methyl orange, methyl red and phenolphthalein is used as an
indicator, strong acid-weak base where methyl orange is used as an indicator, weak acid-strong
base where phenolphthalein used as an indicator and weak acid-weak base titration. To
determine the endpoint and pH the indicators are used. There is another type of titration also.
Non-aqueous titration where water degradable substance is titrated and Aqueous titration where
water is used as a solvent. Substance choice is very important in titration. There are two types of
substance one is primary another is secondary. Primary substances are those substances which
will not be contaminated in environmental exposure and secondary substance are those
substances which will be contaminated in the exposure of the environment. Primary substance is
limited most of the substance found in the environment are secondary substance. Those are
standardized before use in titration. Titration is an easy and simple process which give an
accurate and quick result.[1]

Implication:
  Used to determine the unknown substance pH.
 Determination of the purity of the substance
 Use to determine the nature of the soap
 Use in the food industry, cosmetics industry
 Use in the pathological laboratory for testing the pH level of plasma and urine.
Remark:

Titration has great importance and wisely use process around the world because it is cheap, easy
and accurate. The fastest result can be determined by this method.

ACID-BASE INDICATOR
Introduction:

Acid-base titrations depend on when a mixed solution comes to the neutralization point between
the acid and a base. In addition to the sample, a suitable indicator is added to the titration
chamber which reflects the equivalence point pH range. In simple words, an acid-base indicator
is a compound used to assess whether an aqueous solution is acidic, neutral or alkaline. This
acid-basic indicator is also recognized as a pH indicator as to the colour change with the pH of
the solution. The acid-base indicator indicates the titration endpoint by changing colour. The
endpoint and equivalence point are not the same because the equivalence point is determined by
the reaction stoichiometry while the endpoint is just the change in colour from the indicator. the
indicator error can be minimized by proper selection of the indicator. A pH-meter can be used if
more accurate results are needed.

Description:

Acid-base indicator is a substance which changes its colour according to the pH of the solution.
Indicators are special compounds, since they may occur in two types, each distinctly different in
colour. There is two prominent theory about indicator mechanism. One is the Ostwald theory and
another is the Quinonoid theory. According to the Ostwald theory, indicators are either weak
organic acid or a weak base. The unionized indicator, HIn, has a different colour than the
Unionized formed by the ionization of the indicator in solution, and the degree of ionization of
the indicator defines the indicator's noticeable colour. [1]
 HIn H+ + In (Poorly Dissociated)

Undissociated Color Dissociated Color

Addition of methyl orange in an acidic environment,

HIn In + H+

A H+
HA + Common ion

According to Quinonoid theory, instead of the ionization, the indicator changes its colour based
on intramolecular change or structure.

There is various kind of indicator like methyl red, methyl orange, phenol red etc is used in the
titration. If the desired result is not obtained by the mixture of indicators are used like universal
indicator which is a mixture of Phenolphthalein, Methyl red, methyl yellow, bromomethyl blue
and thymol blue.

Implementation:

There is two major use of acid-base titration. Firstly, indicators are usually used for labelling the
conclusion of a titration. In strong acid and strong base titration phenolphthalein, methyl orange
and methyl orange any of this indicator is used. In strong base and weak acid titration
phenolphthalein is used which turn into ink ate the end of the titration. In strong acid and weak
base indicators like methyl orange and methyl red are used. Secondly, indicators are used to
predict a solution 's pH. example;

indicators End of the reaction pH range pH of solution

methyl red red < 4.8
thymol blue yellow > 2.8 but < 8.0 pH must be between 2.8 and 3.2
 methyl orange red < 3.2
Remark:

The indication of the end of the titration and the pH of the unknown solution are very important
indicators. The pH of the new drug can be determined by titration, without the process of
titration of the indicator.

COMPLEXOMETRIC TITRATION

Introduction:

The technique which involves the titration of metal ions with a complexing or chelating agent
and is commonly called complexometric titration. This technique describes an empirical
implementation of a complexation reaction, i.e. converting a simple ion into a complex ion and
the equivalence point defined by an acceptable process. It is a simple and accurate way to
evaluate metal ions.

Description:

The titration of a metal ion by a complexing agent is, according to the Lewis description, an
acid-base reaction. Complexometric titration follows many principles of acid-base titration. In a
complexometric titration, metals are converted into complex ions and the free metal ions
disappear. The endpoint in acid-base titrations is marked with a sudden change in pH. Similarly,
in EDTA titration, if pM is plotted (negative log of metal ion concentration) v/s volume of
titrant, at the endpoint the pM is rapidly increased. This sudden pM raise results from removal
of traces of metal ions from solution by EDTA. Any method which can determine this sudden
disappearance of free metal ion can be used for detecting the equivalence point or endpoint in a
complexometric titration.
There are many complexometric titration methods. Indirect titration method, A appropriate
buffer solution and indicator are applied to the Mn+ (metal-ion) solution, and the resultant
solution is then titrated with previously formulated disodium EDTA before the indicator changes
colour. There may be several issues with the direct titration of other elements, such a slow
complexation reaction interference due to the presence of other ions. By replacement titration,
the metal from the complex can quantitatively displace. In this method, an excess quantity of
Mg-EDTA chelate is added to Mn solution. Mn quantitatively displaces Mg from Mg-EDTA
chelate. This displacement takes place because Mn forms a more stable complex with EDTA.
The freed Mg metal is then directly titrated with a standard EDTA solution,

Mn2+ + Mg-EDTA2- ↔ Mg2+ + Mn-EDTA2- (replacement step)

Mg2+ + EDTA4- ↔ Mg-EDTA2- + 2H+ (titration step)

Indirect titration is used for the determination of ions such as anions, which do not react with
EDTA chelate.

Implantation of complexometric titration:

Complexometric titration is a simple and accurate way to determine the presence of metal. The
hardness of water, presence of Ca and Mg ion are determined by this method.

Remark:
Complexometric titration is very important. It is widely used in soil and environmental
chemistry. Metal's presence is verified by this method.

NON-AQUEOUS TITRATION
Introduction:
Non-aqueous titration is those in which titration of weakly acidic or basic substances are carried
out using non-aqueous solvents to get sharp endpoint. Some drug degrade in the presence of
water. An example is Arsenic drug, Amide drug etc. For these drugs, non-aqueous titration is
being used.

Description:

Acid is a proton donor and a base is a proton acceptor when acid undergoes a dissociation
process it gives a proton and a conjugated base in the solution. (based on Brønsted-Lowry
Theory).

Based on proton interaction solvents are of 4 types:

Protophilic solvent tends to accept a proton, i.e., water (H2O), alcohol, ammonia (NH3)/liquid
ammonia, etc. Weak acids are normally used in the presence of strongly protophilic solvents as
Their acidic concentrations are thereby enhanced and thus equal to those of strong acids; this is
regarded as the consequence of levelling. Protogenic solvents tend re produce protons, i.e., water
(H2O), liquid hydrogen chloride (HCl), glacial acetic acid (CH3COOH), etc. weak bases strength
are enhanced by them. Amphiprotic solvents are that solvent which has both protophilic and
protogenic nature., e.g., water (H2O), ammonia (NH3)/ammonium (NH4+ glacial acetic acid
(CH3COOH), ethyl alcohol, etc. They are all capable of slight dissociation. Aprotic solvents are
those solvents which neve donate nor accept the proton., e.g., benzene (C6H6), Toluene
(C6H5CH3), carbon tetrachloride (CCl4), Carbon disulphide (CS2), etc.

Non-aqueous titration of weak acid:

Many weakly acidic substances can be titrated in an appropriate non-aqueous solvent with a
sharp endpoint.Ex:- acidic halides, amino acids, enols (barbiturates, xanthenes), phenols,
pyrroles, sulphonamides etc. Solvents used in the titration is weak acid Ex:-Ethylene di amine,
morpholine. Titrant used in the titration of weak acids, Ex:-sodium methoxide, lithium
methoxide, potassium methoxide etc. Indicators used in the titration of weak acids. Like this, for
the acidic reaction of non-aqueous titration, all basic substance is used.

Non-aqueous solvents are useful to titrate very weak acids or bases which cannot be titrated in
water and it is very accurate. But as the solvent are expensive and more care should be taken
about the experiment atmosphere as the solvent can also go through degradation.

Implementation:

It is applied if the compound to be analyzed is poorly soluble in water also used to compare the
strengths of strong acids or bases. When a titration comes to a poor endpoint in a water medium,
non-aqueous titration is used.

Remark:

it is very important when any water reactant product or water degraded substance is used.

REDOX TITRATION

Introduction: This titrimetric method is based mainly on an oxidation change number or

electrons are transferred between the reactants, i.e. they are based primarily on reactions to
oxidation-reduction. In reduced oxidation form of titration, a reduction material is titrated with
normal oxidizing agent solution (e.g., ceric ammonium sulphate) or a solution the oxidizing
substance is titrated with the standard reduction solution agent (for example titanic chloride).

Description:
In oxidation-reduction titrations, the process of oxidation involves the loss of electrons whereas
the process of reduction involves the gain of electrons. The redox titration is based primarily on
the analyte's oxidation the oxidizing agent and the reaction is oxidized and reduced set by
indicators or potentiometric. According to the generalized theory, an increase of oxidation
number happens because of loss of the electron and decrease of oxidation number happens
because of gain of the election, in other words, oxidizing agents undergo reduction and reducing
agents undergo oxidation.
Ce+4 + Fe+2 Ce+3 + Fe+3
Ce+4 + e− Ce+3 (Reduction)
Fe+2 Fe+3 + e− (Oxidation)
The ability of the compound to accept or lose electrons is expressed by the standard electrode
potential. It determines the oxidation or reduction reaction of ions. A sudden change of the
reaction can be detected by a redox indicator. Redox indicator is capable of undergoing oxidation
and reduction.
In(Oxidation) + ne In(Reduction)
Some indicators are specific to the compounds. They react with one of the reactants in the
titration to produce the colour. Example: Starch reacts with the iodine and exhibits a deep
blue colour.
There are many types of titration method. Based on the titrant, potassium
permanganate is used to detect the reducing substance
Example: 2KMnO4 +10FeSO4 + 8H2SO4 5Fe2(SO4)3 + K2SO4 +2MnSO4 +8H2O
Dichromate is used to oxidize the reaction,
Example: 2K2Cr2O7 +6FeSO4 +7H2SO4 3Fe2(SO4)3 +K2SO4
+Cr2(SO4)3 +7H2O
Iodine is also used as the titrating agent.
Based on the method, in a direct titration at the end compound is coloured itself, the
indicator is not needed.
Example: Azo dyes and quinones are titrated by this method.
The titrant solution is added to an over volume to the sample solution and then back to
the excess titrant titled with the other solution of the titrant. This is known as the back
titration method.
Example: Chloramphenicol is titrated by this method.

Implementation :

 Used in dye production

 Used for raw material production and drug synthesis
 It is the standard assay formulation process for unformulated drug and excipients.

Remark: Redox titration is not only used in pharmaceutical but also use in all kind of
chemistry field for determining ions in the solution. The humidity of the air is also measured by
this process.

POTENTIOMETRIC TITRATION
Introduction:

Potentiometric titration can be described as an electrochemical quantitative analytical method in

which an electrochemical cell's potential change is calculated as a function of concentration shift.
By inserting a titrant whose concentration of the test element in the solution Is well known.

Description:[1]

Nernst equation was formulated in 1889. This theory is an important part of potentiometric
titrations, as it relates to the potential of electrochemical cells to the concentration of
electroactive species in the cell. Let’s consider a situation, where a metal M is placed in a
solution containing its ions Mn+. The potential developed after addition of a certain amount of
titrant can be calculated by Nernst equation=𝐸−+𝑅𝑇𝑛𝐹ln𝑎𝑀𝑛+
The accurate, precise and effective potentiometric measurements are made with the aid of the
electrodes namely, reference electrodes and indicator electrode. Reference electrode exhibit a
potential which is independent of the solution wherein it is used. Example,
standard hydrogen electrode, saturated calomel electrode and silver-silver chloride electrode. An
indicator electrode the voltage solely depends on the thermodynamic activity of only one specific
component in the solution Metal indicator electrode, Membrane indicator electrode and the
enzymes-based electrode is an example of indicator electrodes.
The implication of potentiometry:

Ø Can be used for coloured or turbid solution

Ø No indicator is necessary to determine the endpoint

Ø Can be used where the change in potential is too small at the endpoint
 Can be performed automatically
 Can be used with recorders to prepare the titration curve easily

Remark: Potentiometry titration is very significant, not only for the analysis of electrolytes in
clinical chemistry but also for the analysis of NH3 and F- in water in environmental chemistry
also used in food poisoning and agriculture.

Reference:

1. Chatten, L., 2008. Pharmaceutical chemistry. 1st ed. India: Satish kumer.

2. Haque, Nawab, M., 2013. principle of physical chemistry. 2nd ed. Bangladesh: Brothers
publication.