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Fundamental of pharmaceutical analysis-2

Definitions
Solution: is a homogeneous mixture of two or more substances.
Solutes: substances that are dissolved
Solvent: substance in which solutes are dissolved.
Aqueous solution: the solute is a liquid or solid and the solvent is always
water.
Standard solution: is a solution containing precisely known concentration of a
substance
Primary standards are stable chemical compounds that are available in high
purity and which can be used to standardize the standard solutions used in
titrations
Secondary standard is a compound whose purity has been determined by
chemical analysis.
Concentration means the amount of solute per volume unit of solution
10/11/2022 by: Suha Elderderi
Basic calculations and expression of concentrations in pharmaceutical analysis
There are various units used to express amounts and concentrations in pharmaceutical analysis:

Percentage volume/volume (%v/v):

% Volume, is used to express the concentration of liquids in liquid samples (or gases in
gaseous samples).
30 ml of methanol is mixed with 70 ml of water, a 30:70 v/v mixture is
formed (30 % v/v)
Percentage weight/weight (%w/w):
% Weight is used to express the concentration of solids or liquids either in solid samples or
liquid samples

Example: used to express the concentration of active ingredient in a formulation such as a

cream or to express the content of a minor impurity in a drug substance.
a cream containing 10 mg (0.01 g) of drug per gram is a: (0.01/1) 100 = 1% w/w
formulation.
Percentage weight in volume (%w/v):
% Weight/volume is used to specify the concentration of solids or liquids in a solution.

Example: used to express the content of active ingredient in liquid formulations

such as injections, infusions and eye drops.
1 g/100 ml solution of a drug is 1%w/v whether it is dissolved in ethanol or
water.
Parts per million (ppm) calculations

At very low concentrations, it may be convenient to use the terms parts per million (ppm) or
parts per billion (ppb) instead of % weight.

Parts per million (ppm) on a w/w basis is 1 µg/g .

It is a common measure used for impurities in drug substances, particularly heavy metals
and solvents.
1 ppm is also 0.0001%w/w.

10/11/2022 by: Suha Elderderi

 Molarity
is used to express the concentration, which is abbreviated M.
Molarity = number of moles of solute per liter of solution.
Moles = grams of sample (atomic mass)/ molecular weight of sample.

Molar: molecular weight in g/l (mg/ml)

mMolar: molecular weight in mg/l (µg/ml)
µMolar: molecular weight in µg/l (ng/ml)
nMolar: molecular weight in ng/l (pg/ml)

 concentrations also can be expressed as mass per volume unit.

 Preparation of solutions

Solutions can be prepared from either

solid powder or from concentrated
solution.
Preparation of solutions from solid
powder:
-first determine the concentration of the
required solution and its required
volume,
-secondly, a definite weight can be
calculated

𝑤𝑒𝑖𝑔h𝑡=(𝑀 ×𝑉 × 𝑀𝑜𝑙𝑒𝑐𝑢𝑙𝑎𝑟 𝑤𝑒𝑖𝑔h𝑡 )÷ 1000

10/11/2022 by: Suha Elderderi

10/11/2022 by: Suha Elderderi
 Preparation of solution from concentrated solution (dilution) :

- determine the concentration of the

concentrated solution if its molarity is un
known / given its specific gravity, weight
percentage and molecular weight, so its
molarity can be determined from the law
below:

Specific gravity× weight percentage = M ×

MWt /1000
-For preparation of a solution from this
concentrated solution in a specific
concentration, the dilution law must be
followed as: M1 × V1= M2 ×V2
 

10/11/2022 by: Suha Elderderi

Dilution factors:
understanding of dilution factors is fundamental to calculations based on analytical data.

(i) 10 ml of the sample was diluted to 250 ml with water.

(ii) 10 ml of the diluted sample was diluted to 200 ml with water.

What is the dilution factor and the total dilution?

Physical and chemical properties of drug
molecules
acids and bases/ pH/Acid base equilibria in water.
Acids- proton donors
Base- proton acceptors
Neutral- H2O

Acid or Base?
HCl(aq) + H2O(l) → H3O+(aq) + Cl–(aq)

NH3(aq) + H2O(l) → NH4+(aq) + OH–(aq)

 pH
 pH is an expression for the acidity or
alkalinity of an aqueous solution.
 pH is defined as the negative logarithm
to the concentration of the hydrogen ions
(equivalent to the hydronium ions),
[H+].

pH= -log[H+]

pH scale
 Acid base equilibria in water

In pure water the concentration of Hydrogen ions is governed by the equilibrium

+ -
H2O H + OH
Ka
Ka is the dissociation of water and is determined by the
following expression Kw = [H+][OH-] =[H+][OH-] = 10-14.
H2 O

[H+] = [OH-] = 10-7

The pH of water is given by -log 10-7 =7.

  PH = -log [H+]
 POH = -log [OH-]
 PH + POH = 14
 pKa= -log Ka

 the higher the [H+] the stronger the acid, the lower the [H+] the stronger the base.
 Lower pH value stronger the acid, high pH value stronger the base
 Pka also can be used to measure acidic and basic strength
 The smaller pka value stronger the acid, The larger pka value stronger the base
 Strong acids and bases:

 completely ionized in aqueous solution

Strong acid releases protons the [H+] increases

 The extent of dissociation (the amount

of protons released) is a measure of the
strength of the acid.
[H+] for strong acid = [acid]
 HCl (hydrochloric acid) is a strong acid,
because it dissociates completely in
water, generating free [H+] and [Cl-].

 0.1 M HCl contains 0.1 M H+ and has a pH of -log 0.1=1.

Strong base releases hydroxyl the [OH-] increases

For a solution of a strong base such as 0.1 M NaOH, [OH-]= 0.1 M

and [0.1][H+]= 10-14; therefore, [H+]= 10-13 M and the pH of the
solution=13.

Although the pH range is regarded as being between 0 and 14, it

does extend above and below these values, e.g. 10 M HCl, in theory,
has a pH of 1.
 Weak acids and bases

 not completely ionized in aqueous solution and are in equilibrium

with the un-dissociated acid or base

as is the case for water, which is a very weak acid. The dissociation
constant Ka is given by the expression below:
Examples
In a 0.1 M solution of acetic acid In a 0.1 M solution of ammonia
(Ka= 1.75×10-5), the equilibrium (Kb=1.8×10-5), the equilibrium can be
can be written as follows: written as follows:
 Henderson–Hasselbalch equation:
For Acid For base
From this relationship for acetic acid it is
possible to determine the degree of
ionisation of acetic acid at a given pH.
Thus, when the pH= 4.76, pka =4.67 then:
Acetic acid is 50% ionized at pH 4.76.
 For example, when ammonia (pKa 9.25) is in
a solution at pH 9.25, the Henderson–
Hasselbalch equation can be written as
follows:
Ammonia is 50% ionized at pH 9.25
 Buffers:

Buffers can be prepared from any weak

acid or base and are used to maintain
the pH of a solution in a narrow range.

This is important in living systems; for

example, human plasma is buffered at pH
7.4 by a carbonic acid/bicarbonate buffer
system.

 Buffers are used in a number of areas of analytical chemistry,

such as the preparation of mobile phases for chromatography
and the extraction of drugs from aqueous solution.
 Preparation of buffers

 Buffers can be prepared from any weak acid or base

 the simplest type of buffer is composed of a weak acid or base in combination with a
strong base or acid.
 Buffer solutions usually consist of solutions containing a mixture of a weak acid HA
and its sodium or potassium Salt (A-), or of a weak base B and its Salt (BH').

 The buffer resist large changes in pH by absorbing the H+ ions or OH- ions added to
the system.
 When H+ ions are added to the system they will react with the conjugate base in the
buffer .
 When OH- ions are added they will react with the conjugate acid in the buffer

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 A common buffer system is the sodium acetate/acetic acid buffer system.
 The most effective range for a buffer is 1 pH unit either side of the pKa value of the weak
acid or base used in the buffer
 The pKa value of acetic acid is 4.76; thus its effective buffer range is 3.76–5.76
 the most direct way of preparing this buffer is by the addition of sodium hydroxide to a solution
of acetic acid until the required pH is reached.
- Ionization of acetic acid:
OH H2 O
Resisting changes

-
Acetic acid HAc Ac Acetate
-
(CH3COOH) (CH3COO )
• Some weak acids and bases have more than one buffer range;
• for example, phosphoric acid has three ionisable protons with three different pKa
values and can be used to prepare buffers to cover three different pH ranges.
• The ionic species involved in the ranges covered by phosphate buffer are:

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 buffering capacity
 The resistance of a solution to changes in hydrogen ion concentration upon the
addition of small amounts of acid or alkali is termed buffer action;
 Quantitative measure of the resistance to pH changes is called buffer capacity, the
ability of the buffer to resist changes in pH when an acid or base is added.
it can be defined as the number of moles of H+/OH- ions that must be added to
one liter of the buffer in order to decrease /increase the pH by one unit
respectively.
buffer capacity is directly proportional to the buffer concentration.

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 Salt hydrolysis

Salts may be divided into four main classes:

(1) those derived from strong acids and strong bases, e.g. potassium
chloride;
(2) those derived from weak acids and strong bases, e.g. sodium
acetate;
(3) those derived from strong acids and weak bases, e.g. ammonium
chloride; and
(4) those derived from weak acids and weak bases, e.g. ammonium
formate or aluminium acetate.

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• When the salt of a strong acid and a strong base is dissolved
in water it produces a pH of 7.0.

• When salts of a weak acid and a strong base or of a strong

acid and a weak base are dissolved in water, they will
produce, respectively, alkaline and acidic solutions.
 Calculation of pH of salt of weak acid and base

the acetate ion behaves as a base,

When sodium acetate is dissolved in water
removing protons from solution.

The ammonium ion behave as an acid ,

When ammonium chloride hydrolyzed in increase
water protons in solution

For a weak electrolyte in water,

Kb × Ka= Kw.
Calculate pH of 0.1 M solution of sodium acetate in water is considered:
Thanks for your attention