INTRODUCTION TO QUALITY CONTROL

The term “quality” as applied to a drug product has been defined as

the sum of all factors which contribute directly or indirectly to the
safety, effectiveness, and reliability of the product. These properties
are built into drug products through research and during the manufacturing
process by procedures collectively referred to as “quality control.”Quality
Control guarantees within reasonable limits that a drug product:

(1) is free of impurities

(2) is physically and chemically stable

(3) contains the amount of active ingredient as stated on the

label, and

(4) provides optimal release of active ingredients when the product is

administered.
 Four Classes of Reagents in the Laboratory

1. Technical or Commercial Grade – the cheapest kind. They

have not been purified very well and can’t be used for
quantitative work.
2. USP Grade – these have been purified to conform with the
standards set by the USP book. They are used in
compounding medicines and dispensing prescription in
drugstores.
3. Chemically Pure or CP grade – these have undergone a very
thorough purification. The quantity of impurity is very small.
This can be used for quantitative work.
4. Analytical Reagent or AR grade – the most expensive class of
reagent, besides being thoroughly purified. They have been
analyzed carefully so that every bottle carried on the label a
complete analysis of the compound.
 Types of Solution Based on Concentration

1. Concentrated Solution – a solution containing a relative large

amount of solute.
Examples: Pure HCl – 37% pure & 12N
CP H2SO4 - 98% pure & 36N
Conc. HNO3 – 65% pure & 16N
Conc. NH4OH – 28% pure & 14N
2. Dilute Solution – a solution containing a small amount of solute
3. Saturated Solution – a solution containing the maximum
amount of solute that the solvent can dissolve.
4. Unsaturated solution – a solution containing less solute that
what a given volume of solvent can dissolve.
5. Supersaturated Solution – a solution containing more solute
that what a given volume of solvent can dissolve.
 Ways of Expressing Strength of Solution

1. Weight/unit Volume – expresses the weight of solute in grams per ml of solution.

Ex. 2 grams BaCl2 / ml

2. Specific gravity – this is used for alcoholic solution which is numerically equal to
density.
Density = specific gravity
D = w/v; specific gravity = weight/ volume
Examples:
a) What is the weight in grams of 10 ml H2SO4 whose sp. gr. is 1.84?
10ml g H2SO4 = 18.4 g H2SO4
b) What is the volume in ml of 12 grams HCl whose sp gr is 1.15?
12 g HCl = 10.43 ml HCl

3. Ratio – proportional amount or parts of solute compared to the proportional

amount or part of solvent

4. Percent strength – expresses the number or weight in grams of solute present

in 100 ml of solution.

% strength = weight in grams of solute x 100

Volume in ml
 Examples:
1. What is the % strength of a ½ liter NaCl solution containing
8 grams of solute?
2. How many ml of a 2% Iodine solution can be prepared out
of 22 grams iodine crystal?
3. How many grams of silver nitrate will you need to prepare 1
liter of a 5% silver nitrate solution?

5. Molar solution – a solution containing one gram

molecular weight of solute in one liter of solution.
Examples:
1. If 28 grams of KOH are dissolved in q.s. water to make a
liter solution, what is the molarity of the above solution?
2. How many grams of silver nitrate will be needed to prepare
400 ml 0f 0,25 M solution?
6. Normal solution – a solution containing one gram equivalent
weight of solute in liter of solution.

GEW =molecular weight

- no. of replaceable H+ in acidic compounds
- no. of replaceable OH- in basic compounds
- total + valence in neutral salts OR
- no. of electrons gained or lost in REDOX

Determination of milliequivalent weight (meq wt)

Meq wt = 1/1000 of an equivalent weight OR
Meq wt = Eq wt/1000 OR
Meq wt =molecular weight
- total no. of + valence
- no. of H+ X 1000
- no. of OH-
- no. of electrons gained or lost
Examples:
SALTS ACIDS BASES

NaCl HCl KOH

Na2SO4 H2SO4 Ba(OH)2
CaCl2 H3PO4 Al(OH)3
AlCl3 CH3COOH Mg(OH)2
Na2PO4
KCl
Na2CO3
STOICHIOMETRY INVOLVING
NORMALITIES
N= Weight of substance
Volume in ml x meq wt

Example/s:
1. What is the normality of a solution which
was prepared by dissolving 3.7 grams of
Ca(OH)2 in q.s. water to make 100 ml
solution?

2. How many grams of KOH are needed to

prepare one liter of a 0.25N solution?
 Methods of Analysis in Quantitative Pharmaceutical
Chemistry may be divided according to the following procedures:
I. General Methods used in official Pharmaceutical Analyses:

1. Volumetric (Titrimetric) Methods – is the determination of the

volume of a solution of known concentration required to react with a given
amount of the substance to be analyzed.

Preliminary Consideration:
4 requirements in Volumetric Work
1. accurate balance for weighing the sample
2. accurate measuring instrument for measuring volume (burets,
pipets and volumetric flask)
3. a standard solution (ss) or a solution whose accurate
concentration is known
4. An appropriate indicator
 NEUTRALIZATION METHODS :
Indicators used in Neutralization Method:

INDICATORS ACID ALKALINE NEUTRAL

Phenolphthalein Colorless Dark pink / red Light pink

Methyl Orange Red-orange / pink yellow Salmon-pink

Methyl Red Red Yellow Orange

 Rules governing the use of Indicators:

a. Unless otherwise specified, use only 2 drops of indicator

b. In the titration of strong base with strong acid any of the

three (3) indicators may be used.

c. In the titration of weak base with strong acid, methyl

orange is used.

d. In the titration of weak acid with strong base,

phenolphthalein is used.

e. Never titrate a weak base with a weak acid. No indicator

will give a sharp end point color.
STEPS INVOLVED IN VOLUMETRIC
ANALYSIS

A. PREPARATION

B. COMPARISON

C. STANDARDIZATION

D. ACTUAL ANALYSIS
 STEPS INVOLVED IN VOLUMETRIC ANALYSIS
A. PREPARATION – computations involved

1. From a solid
Weight = N x V x meq wt
Ex. Solve for the weight needed to prepare 1 liter 0.50 N potassium hydroxide
solution.

2. From a solution of known specific gravity and % strength

V = N x V x meq wt
Sp. gr. x %/ 100
Ex. How many ml of sulfuric acid whose sp. gr. Is 1.84 which is 98% pure will
be diluted with water to prepare ½ liter of 0.5 N solution?

3. From a solution of known normality by dilution with water.

N1 V1 = N2 V2
Ex. Solve for the volume of concentrated HCl which should be diluted with
water to produce 500 ml of 0.5 solution.

4. By mixing two solution of known normality (solve by allegation)

Ex. How many ml of 6N of 2N sulfuric acid will be mixed to produce 100 ml of
4N sulfuric acid
B. COMPARISON – after a pair of solutions have been prepared, their
concentrations are then compared with each other. Their relative
concentration are expressed in terms of the ratio of concentration.

1. Determination of the ratio of concentration - the concentration of the prepared

solutions are still inaccurate and are therefore, can’t be expressed accurately in
terms of the ratio of concentration . The ratio can then be determined by comparing
accurate volumes of the prepared solution and then applying the formula as derived.

If Va is a known volume of acid which is titrated with the base and the volume of base is Vb,
then we say the end point of titration Va = Vb

At end point Na Va = Nb Vb

where: Na = normality of acid

Va = volume of acid
Nb = normality of base
Vb = volume of base
To (express) compare accurate volumes in terms of one ml:

1 ml A = Vb
Va

1 ml B = Va
Vb

Example: If 10 ml HCl is titrated to end point by 12.2 ml of NaOH,

1. What is the equivalent of 1 ml HCl in terms of NaOH?

2. What is the equivalent of 1 ml NaOH in terms of HCl

2. Use of the ratio

1. For converting volumes in back titration

Ex. A sample of Na2CO3 when titrated with 26.4 ml of HCl

but then the end point was over stepped and 1.8 ml of
NaOH was used in the back titration to get the correct end
point. If 1 ml HCl = 0.88 ml NaOH, what is the correct
volume of HCl that was used to titrate the Na2CO3
sample?

2. For determination of N, if the N of the other solution is

given.

Ex. If 1 ml HCl = 0.88 ml NaOH and the normality of NaOH is

0.28N, what is the N of HCl?
 C. STANDARDIZATION

• process of establishing the accurate

concentration of a solution by allowing it to
react with a pure substance known as
primary standard. (pure substance used to
establish the accurate concentration of a
solution
 PREPARATION AND STANDARDIZATION OF ACID
SOLUTIONS

• Normal hydrochloric acid solution may be standardized

titrimetrically against pure sodium carbonate or standard
solution of sodium hydroxide which has been recently
standardized, or gravimetrically by precipitation of an
equivalent amount of silver chloride. (Refer Jenkin’s
Quantitative Pharmaceutical Chemistry pages 72-73,
Exercise 3.1).

• The normality may be calculated as follows:

ml x N = meq

N = wt of primary standard
ml x meq
Examples:

1. If 30.20 ml of hydrochloric acid solution were required in the

titration of 0.3060 g pure sodium carbonate, what was the
normality of the acid?

Reaction involved:

Na2CO3 + 2HCl --------------- 2NaCl + H2O + CO2

2. In the standardization of HCl against pure anhydrous sodium

carbonate using methyl orange as indicator , 1 ml HCl was found
to be equivalent to 0.050 g of sodium carbonate (Mw=106). What
is the normality of HCl?

Reaction involved:
 Aqueous Medium:

Types of Neutralization Reactions:

1. Acidimetry – acidic titrant with basic analyte
2. Alkalimetry - basic titrant with acidic analyte

Types of Titration in Neutralization Methods:

1. Direct Titration
2. Residual or back titration
 Direct Titration
 is conducted by introducing a standard a
standard acid solution gradually from a buret
into a solution of the base being assayed until
chemically equivalent amounts of each have
reacted as shown by some change in properties
of the mixture. Such an end point, which must
be close to the stoichiometric point, is made
evident by a change in the color of some
indicator. The percent purity may be calculated
as follows:

% = ml x N x meq x 100
Sample
Examples:
• Calculate the sodium Bicarbonate content of 0.2800 g
sample requiring 3.51 ml of 0.9165 N sulfuric acid.
Solution:
% = ml x N x meq x 100
Sample
 Residual or back titration
is used whenever the end point of a direct
titration deviates appreciably from the
stoichiometric points for some reason;

 when the reaction proceeds slowly

 when the reaction doesn’t give a sharp end-
point with the indicator
 when the sample or analyte cannot be brought
to solution without changing the
chemical nature upon which the titration
is based.
 Residual titration is carried out by dissolving the substance
under examination in an accurately measured quantity of standard
solution known to be in excess and titrating the excess of the
latter with another standard solution. The percent purity of the
sample may be calculated as follows:

% = (mla x N) – (mlb x N) x meq wt x 100

Sample wt
Examples:

1. A 1.2500-g sample of zinc oxide were treated with 50 ml of

1.1230 N sulfuric acid and 27.48 ml of 0.9765 N sodium
hydroxide were consumed. Calculate the percent purity of the
sample.

2. Calculate the MgO content of milk of magnesia, 12.32 g which

was dissolved in 50 ml of 1.0340 N sulfuric acid, producing a
mixture that required 24.60 ml of 1,1265 N sodium hydroxide.