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Electrochemical Method
A Potentiometry
Branch of electrochemistry
which deals with the study and
measurement of electrode
potential
Potentiometer
Tool used in potentiometry
APPLICATION
- pH determination
- titration endpoint
A.1 Electrode Potential
electric potential difference
between an electrode and
surrounding electrolyte solution
when no current is flowing
through the cell
Standard Electrode
Potential
electrode potential measured
under standard conditions
o Concentration: 1M
o Temperature: 25C
o Pressure: 1atm
Top 5 strongest oxidizing
agents
- Fluorine
2. H2O
- MnO
- Chlorine
- Cr2O
Top 5 strongest reducing
agents
- Li
- Na
- Al
4. 2H
- Zn
A.2 Principle
When the pair of electrodes is
placed in the sample solution it
shows the potential difference
by the addition of titrant.
A.3 Electrode
Used to measure voltages
o Reference electrode
o Indicator electrode
Reference Electrodes
Known potential
Primary standard electrodes
Standard
Hydrogen
Electrodes
Platinum
wire in
inverted
glass tube
EP is ZERO
at all temp
Secondary standard
electrodes
Silver-silver
chloride
Electrode
Most widely
marketed
reference
electrode
KCl saturated
with AgCl
Saturated
Calomel
Electrode
Hg at
bottom
covered with
solid HgCl
EP:
+0.2422V
Indicator Electrodes
Unknown potential
Potential sensitive to
concentration of analyte
Potential is directly proportional
to the ion concentration
Glass
Electrode
pH
measurement
Ion-selective
Electrode
Drug assay
Redox
Electrode
REDOX analysis
Quinhydrone
Electrode
Selective pH
measurement
Ion Selective Indicator
AKA: SIE (Selective Ion Indicator)
Consists of a thin membrane
where only ion can be
transported
Glass Electrode
Most widely used indicator
electrode
Selective
Responsible for changes in
concentration of hydrogen ions
Advantages Disadvantage
s
- Rapid
response
- Chemically
resistant to
REDOX
agents
- Can be
easily
broken or
damaged
- Minute
abrasions,
damage the
electrode
Quinhydrone Electrode
Least expensive
Equimolar mixture of quinone
and hydroquinone, and a
platinum foil electrode
Potential depends on pH
Acidic or organic solvent-
based solutions
and determines its degree of
acceptability
Measurable Criteria
Conforman
ce
Being within
prescribed
Fitness for
use
Functionality
Reliability Function in
specified
environment for a
prescribed length
of time
Yield High degree of
acceptable units
Customer
satisfaction
Product is safe,
pure, and
effective
B Standards
Pharmacop
eial
Published
monographs
USP/NF, BP, EP
Identity,
physical tests,
alcohol
content, etc.
Regulatory Mandated by
regulatory
agencies
FDA, WHO
Labelling
requirements
In-House Unofficial
In compliance
to GMP
Generated by
manufacturer
Standards must cover the
FF:
1. Formula
a. In-house
b. Pharmacopeial
standard
2. Raw Material Specification
[RMS]
a. Characteristics are
pharmacopeial
b. International standard
3. Standard Operating
Procedures
a. Says how to do the
procedure
b. Can be in house or
pharmacopeial
4. Finished Product
Specification
a. Ready to market
b. Based on regulatory
standard
5. Packaging Material
Standard
a. In-house
6. Testing Method
a. Pharmacopeial and in-
house
b. Can make own method
but must be
standardized and
validated
C QM; QA; GMP; QC
C.1 Quality Management
Quality policy
Intention to have a quality
product
Total Quality Management
Combined team effort
C.2 Quality System
Infrastructure; organizational
structure
C.3 Quality Assurance
Overall systemic action to meet
the quality policy
Totality of the organized
arrangements
C.4 GMP
Good Manufacturing Practices
Part of QA
Tool to meet quality of the
product
C.5 Quality Control
Part of GMP
Test if you have a good quality
product
D Other Def. of Terms
Product Quality Review
(PQR)
Regular periodic quality reviews of
all registered drug products
Identify product and process
improvements
Quality Risk Management
(QRM)
Systematic process for the
assessment, control,
communication, and review of
risks to the quality of the
product
E Documents
Monograph
Specifies all tests to be
conducted and the expected
results
Standard Operating
Procedure
Shows the actual result of all
tests conducted on a material
to show compliance with
standards
Material Safety Data Sheet
(MSDS)
Contains information on the
potential health effects of
exposure to chemicals and on
safe working procedures when
handling chemical products
E.1 Official References
- USP-NF
- Japan Pharmacopeia
- British Pharmacopeia
- European Pharmacopeia
high value = trivial
defects
based on the master table
N plan/ Square root system
F.2 Government Sampling
Plan
Master table is used to
know then, AC and Re
Two tables:
- table for sampling by
attributes
a. MIL-STD-105D 105E
b. ABC-STD- 105D
- table for sampling by
variables
a. MIL-STD-
Required information
i. Batch size, AQL and
sample size code letter
ii. Method of sampling
inspection
iii. Inspection scheme:
normal, tightened or
reduced
G Statistical Quality
Control
Monitoring of quality by
the application of
statistical methods in
all stages of production
Consist of proper
sampling,
determination of
quality variation and
making inferences of
the entire batch
Quality Control Charts
- Attribute Chart
Discrete data
classifying no. of items
conforming and not
conforming to any
specified requirements
P chart (fraction
defective)
- Variable Chart
Actual records of
numerical
measurement on a full
continuous scale
X, R charts
G.1 Control Chart
Graphs on which the
quality of the product is
plotted as
manufacturing is
actually proceeding
Types
P-chart Proportion of
defectives
Np-chart Non-proportion (no.
of defectives)
X bar
chart
Used for measurable
characteristics
Warning limit
Alerts the operator to
closely monitor the
process
Action limit
Alerts the operator to
stop the process and
do corrective action
H Validation Vs
Qualification
Validation action of proving
and documenting
that any process,
procedure or
method actually
leads to the
expected results
Qualificati
on
action of proving
that premises,
systems or
equipment work
correctly and
actually lead to
expected results.
H.1 Types of Validation
1. PROCESS VALIDATION
2. ASSAY VALIDATION
it is established by
laboratory studies that
the performance
characteristics of the
method meet the
requirements of the
intended analytical
applications
Sources of errors:
o Gross
o Random
o Systematic
3. VALIDATION OF
MANUFACTURING
EQUIPMENT
4. VALIDATION OF EXISTING
PRODUCTS
Related to the efficiency of
the product
o (potency, content
uniformity, dissolution/
bioavailability)
Concern with processing
characteristics
o (Moisture content,
weight variation)
5. CLEANING VALIDATION
Utilized instruments that can
detect microgram levels of
contaminants form product
and detergent residue
6. POST-VALIDATION
H.2 Product Defects
Non-conformance to a
standard or requirement
Classifications
According to magnitude
Critical
defect
May endanger life
of patient
Major
defect
Does not endanger
but affects function
of product
Factors
Drugs are mainly
decomposed by:
Hydrolys
is
Prevented by
reduction or
elimination of water
from the preparation
Oxidatio
n
Prevented by
antioxidants
Photolys
is
Prevented by using
light-resistant
containers
J.2 Shelf-life
Period of time during which a
product is expected to
remain within specification
Estimated using the
Arrhenius equation
REASSAY
Unstable Monthly, prior
to use
Vitamins 6 months
Drugs &
dyes
1 year
Drugs & 2 years
excipients
Shelf-life/
reformulation?
Highly
unstable
Months or prior
to use
vitamins 6 months
Drugs &
Dyes
1 year
Drugs &
excepients
2 years
J.3 Expiration Date
Time/date to which a product
is expected to remain stable
and after which it must not
be used
Formula
ED= MD + SL
ED: expiration date
MD: manufacturing date
SL: shelf life
Climatic zone
Philippines: Zone IVB
Types of stability studies
Long-
term
studies
Normal conditions
Period : 0, 3, 6, 8,
Accelerat
ed
studies
Increase the rate of
chemical
degradation by using
exaggerated storage
conditions
Period: 0, 3, 6
Stress
testing
Elucidates the
intrinsic stability of
the drug substance
and identify the
likely degradation
products
More severe
conditions
Electrochemical Method
A Handling of Raw
Material
A.1 Quarantine
Status of materials which are
isolated physically while a
decision is awaited on their
release, rejection or
reprocessing
Yello
w
Quarantine materials
Gree
n
Conform to tests
Red Rejected
A.2 Warehouse Distribution
Practices
- First in-First out [FIFO]
move first stocked products/
products bought first
E Physical Tests
Can be used for identification
and determination of
concentration of a
component
Used to determine the
presence of impurities
E.1 Specific Gravity
Ratio of the density of a
substance to a reference
o 25C
Pycnometer or Mohr-
Westphal balance
Alcohol
Measured using a hydrometer
at 15.16C
E.2 Refractive Index (n)
Ratio of the velocity of light
in the air to the velocity of
light in the substance
o 25C
Abbe refractometer
Formula
N = sin I / sin r
[i= angle of incident; r = angle of
refracted ray]
E.3 Optical Rotation (a)
Measure of its ability to
rotate an incident plane of
polarized light
Dextrorotatory or
levorotatory
Polarimetry
E.4 Solubility
EXAMPLE QUESTION
WHAT IS THE SOLUBILITY OF A
DRUG IF IT REQUIRES 100ML OF
SOLVENT
PER 100MG OF DRUG?
Solution:
Solubility = 100mg/100mL
Determine how many mL
per 1gram solute (1000mg)
100mg = 0.1g
0.1g/100mL=1g/x
x = 100ml/0.1g
x = 1,000 mL/g
Solubility = 1,000 parts
Therefore, the solution is very
slightly soluble
E.5 Boiling/ Freezing Point
Indicates presence of
impurities
E.6 Loss on Drying
Determines the amount of
volatile matter driven off
after drying
E.7 Water Determination
(official Methods)
Karl-Fischer Titrimetry
Based on the reaction of
water and KFR
KFR Components
Sulfur dioxide Main
component Iodine
Pyridine
Anhydrous
Methanol
Types
Method IA Direct
Method IB Residual
Method IC Coulometric
Azeotropic Distillation
Based on distillation of water
Toluene or Xylene
(alternative)
Toluene-moisture apparatus
Gravimetry
Based on loss on drying
Inorganic
materials
110-120C
Organic
materials
105C
Water Content
