QCCC
QCCC
Quality Control
Quality – as applied to drugs 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 qualities are built into the product
through research and during the
manufacturing process by procedure
collectively referred to as quality control
Quality Control
• QC guarantees :
– Drug is free from impurities
– Physically and chemically stable
– Contains amount of active ingredients as stated on
the label
– Optimal release of active ingredients when the
product is administered
Quantitative Pharmaceutical
Chemistry
• The application of the procedures of
quantitative analytical chemistry
1. To the analysis & determination of the purity and
quality of drugs and chemicals used in pharmacy
2. To the analysis of the chemical constituents
found in the human body whose altered
concentrations during the disease states serve as
diagnostic aids in the practice of medicine
3. To the analysis of medicinal agents and their
metabolites found in biological systems
Analytical Chemistry
• Branch of chemistry involved with the analysis
of chemical components
• 2 kinds:
1. Qualitative chemical analysis – is the
identification of the component in the
sample/product.
2. Quantitative chemical analysis- determination of
the amount/concentration
Quantitative Pharmaceutical Analysis
• A. Volumetric Method of Analysis
1. Chemical indicator methods
a. Neutralization
b. Redox
c. Precipitation
d. Complexation
• B. Gravimetric Method of Analysis
• C. Special Methods Used in Pharmaceutical
Analysis
Review on Some Basic Principles
• Expression of Concentration
• Molarity – expression of concentration in
terms of moles of solute per liter of solution
• A Molar solution is a solution containing 1-
gram molecular weight of solute per liter of
solution
Review on Some Basic Principles
• Normality – expression of concentration in
terms of equivalents of solute per liter of
solution
• Normal solution containing 1-gram equivalent
weight of solute per liter of solution
• Equivalent is the quantity of a substance that
is chemically equivalent to 1.0079g of
Hydrogen or Hydrogen ions
Review on some basic principles
• Gram-equivalent weight (GEW) is defined as
that weight in grams which is chemically
equivalent to 1 gram – atom of hydrogen
(1.0079)
• In neutralizing reactions:
– It is defined as the weight of substance in grams
which contains, furnishes, and reacts with directly
or indirectly, replaces 1 gram – atom or ion of
hydrogen
Quantitative Pharmaceutical
Analysis
• A. Volumetric Method of Analysis
1. Chemical indicator methods
a. Neutralization
b. Redox
c. Precipitation
d. Complexation
• B. Gravimetric Method of Analysis
• C. Special Methods Used in Pharmaceutical
Volumetric/Titrimetric Method of
Analysis
• May be defined as those analytical methods in
which the volume of a solution of known
concentration consumed during an analysis is
taken as a measure of the amount of active
constituents in a sample being analyzed.
• Titration – the process whereby a standard
solution is brought into reaction
• Titrant also known as the standard solution is
the solution of known concentration
• Analyte is the substance being analyzed.
• Indicator is usually a chemical which changes
its color at or very near the point in the
titration where equivalent amounts of analyte
and titrant have reacted.
• Equivalence point – point at which the
reaction is exactly completed.
• End point where the titration actually stops at
which occurs a sudden change in some
property of the reaction mixture.
Volumetric method of analysis
• Types of titration
1. Direct titration (one titrant)
ex. Assay of HCl using NaOH as the titrant
2. Residual or back titration (2 titrants)
ex. Assay of ZnO
Result in the drug assay is expressed in:
% w/v;
% v/v;
% w/w
• Titrations may be conducted by:
1. Direct titration- is the treatment of a soluble substance,
contained in solution in a suitable vessel (the titrate)
with an appropriate standard solution (the titrant), the
endpoint being determined instrumentally or visually
with the aid of a suitable indicator.
2. Residual titration is the addition of a measured volume
of a volumetric solution, in excess of the amount
actually needed to react with the substance being
assayed, the excess of the solution then being titrated
with a second volumetric solution. This constitutes a
residual titration and is known also as back titration.
• What is the % w/w of sodium hydroxide
(MW40) in 1.5 sample of soda if it uses 15.25
mL of 0.5N HCl in the titration using
phenolphthalein as the indicator?
N x V x mEq wt
% w/w = --------------------------- x 100
weight of the sample
• If a sample of sodium carbonate (MW106) weighing
1.932g required 32.10 mL of HCl in the titration,
what is the normality of the acid?
wt of the solute (analyte,sample)
1) N = ---------------------------------------
volume (mL) x mEq wt (solute)
Na x Va = Nb x Vb
number of mEq
N = ---------------------------
Volume (mL)
• Organic material
• Converted to
NH4HS04
Added w/ excess strong NaOH
• Primary standard
– Benzoic acid
Indicators:
• Thymol blue
• Azo violet
• o-Nitroaniline
Precipitation and Complexation
Methods of analysis
• Volumetric precipitimetry requires the
formation of relatively insoluble substances or
precipitates to cause the reactions to go to
sufficient completion to be quantitative in
nature.
• Determination of end point
• Cessation of precipitation or the appearance
of a turbidity
• Use of internal indicators
• Instrumental methods
• Indicators
– Ferric ammonium sulfate
– Potassium chromate
– Adsorption indicators
• Standard solutions
– 0.1 N silver nitrate
– 0.1N ammonium thiocyanate
Standardization of Silver Nitrate
• Diluted HCl
Chemical reaction :
AgNO3 + HCl AgCl + HNO3
white curdy ppt
Standardization of Ammonium thiocyanate
Chemical reactions:
AgNO3 + NH4SCN AgSCN + NH4NO3
White ppt
• EDTA titrations
• Indicators
– EDTA titration indicators are organic compounds
which form colored complex ions with the metal
ion in high dilution
• Indicators used in EDTA titrations
– Hydroxynaphthol blue (hnb)
– Eriochrome black
– Pyridylaxonaphthol
– Xylenol (xyo) orange
• Preparation and standardization of 0.05M
Disodium Ethylenediaminetetraacetate
– Primary standard : Calcium carbonate
– Indicator: hnb
– End point : blue
• Masking – determination of metal in the
presence of another metal
• Mechanism of masking – It is accomplished by
adjusting the pH titration medium so that it
will be favorable to the metal being
determined.
• Residual titrations (standard Solutions)
– EDTA
– ZINC SULFATE
• Metal ions
– Ca++, Mg ++, Zn++ (direct titration)
– Bi+++, Al+++ (residual titration)
Oxidation – Reduction Reaction
• Rules in assigning oxidation number:
1. The oxidation state of an element in free
state is zero (0).
This includes polyatomic elements.
2. The oxidation state of a monoatomic ion
is the same as the charge on that ion.
a) alkali metal ions are always +1
b) alkaline earth ions are always +2
3. The halogens are in a -1 oxidation state
in binary (2 element) compound
4. Oxygen in a compound is usually -2. certain
compounds called peroxides or superoxides
contain O in a lower negative oxidation state.
5. Hydrogen in a compound is usually +1
• Ceric sulphate
• Iodimetry
• Iodometry
• Permanganate methods
Characteristics:
• Reaction of permanganate is solution are
rapid
• Potassium permanganate serves as indicator
itself
• Oxidation-reduction reaction methods of
analysis involve a change in valence of the
reacting substances
• Oxidizing agent – is the reactant that gains
electrons in the redox reaction. It is identified
by the decrease in oxidation state. KMnO4
mEq wt. = MW
____________
no. of e gained x 1000
• Example.
• KMnO4 - oxidizing agent
KMnO4 + 5e Mn++
• Reducing agent:
Eq wt = MW
__________
no. of e lost
mEq wt = MW
_____________
no. of e lost x 1000
• Sodium oxalate – reducing agent
Na2C2O4 2CO2 + 2e
• Permanganate process
• Characteristics:
– Can be standardized easily
– It retains its concentration over a long period of
time when proper precaution are observed in its
preparation and preservation
– Reaction of permanganate in solution are rapid
– It serves as the indicator in titration
• Permanganate Methods
• Standardization of Potassium permanganate
• Primary standard – sodium oxalate, since it can
be obtained in a very pure condition
• Sufficient sulfuric acid must be added to keep
the hydrogen – ion concentration reasonably
constant throughout the titration, thereby
preventing the formation of manganese dioxide
and supplying the hydrogen ions used up in the
reduction of the permanganate ion.
• For every mole of permanganate ion reduced, 8
mol of hydrogen ion is required.
The half-reactions are:
• Loss on Ignition
Provides a means of determining the percentage of
test material which volatilized and driven off
under condition specified.
wt of sample – wt of ash
% LOI = --------------------------------- x 100
wt of sample
Water content:
Forms of water in drugs:
1. Water of crystallization
2. Water in the adsorbed form
Water content is generally determined by one of 6
methods:
1. gravimetric, for drugs containing no constituents,
other than water, volatile at 105°C
2. Gravimetric, for drugs containing ether-soluble
constituents volatile at 105°C
3. Azeotropic (toluene distillation)
4. Titrimetric (Karl Fischer)
5. Dew point
6. Electrolytic hygrometric
Extractive and Crude Fiber Content
Different methods of extraction
The Soxhlet Apparatus for extraction