Pharmaceutical Analysis

2. Potentiometry
BY ABRAR AHMAD

3. Electroanalytical methods
 Electroanalytical methods are a class of techniques in analytical
chemistry which study an analyte by measuring the potential (volts)
and/or current (amperes) in an electrochemical cell containing the analyte.
 These methods can be broken down into several categories depending on
which aspects of the cell are controlled and which are measured.

4. Types of Electroanalytical methods
 The four main categories are
1. Potentiometry (The difference in electrode potentials is measured)
2. Polarography (Determine the concentration of substances in solution by
measuring the current flowing through an electrochemical cell)
3. Coulometry (Charge passed during a certain time is recorded)
4. Voltammetry (The cell's current is measured while actively altering
the cell's potential).

5. Introduction to Potentiometry
 Potentiometry is a fundamental electrochemical technique
widely employed in pharmaceutical analysis for the quantitative
determination of ions in solution.
 It relies on the measurement of the potential difference (voltage)
between two electrodes immersed in the sample solution.

6. Principle of potentiometry
 Based on the measurement of electrical potential difference (voltage) between two
electrodes in a solution.
 One electrode is called the reference electrode and has a constant potential, while the
other one is an indicator electrode whose potential changes with the sample's
composition.
 Therefore, the difference in potential between the two electrodes gives an assessment
of the sample's composition.

7. Principle of potentiometry
 This reaction is typically specific to the analyte being measured.
 As the concentration of the analyte changes, the potential difference
between the electrodes also changes proportionally.
 Relationship between the potential difference (E) and the concentration
(C) of the analyte in solution is described by the Nernst equation.

8. Nernst equation
 The Nernst equation, formulated by German physical chemist
Walther Nernst in 1889, describes the relationship between the
electrochemical potential of an electrochemical cell and the
concentrations of the species involved in the redox reaction.
 The Nernst equation is typically written as:

9.  E is the cell potential (voltage),
 E∘ is the standard cell potential under standard conditions (usually at 25°C and 1 atm),
 R is the gas constant (8.314 J/(mol·K)),
 T is the temperature in Kelvin,
 n is the number of moles of electrons transferred in the redox reaction,
 F is Faraday's constant (96,485 C/mol), and
 Q is the reaction quotient, defined as the ratio of the concentrations of the products to
the concentrations of the reactants in the electrochemical reaction.

11. TYPES OF ELECTRODES
 Electrodes are essential components in electrochemical measurements,
serving as conductive interfaces between the electrolyte solution and
the electronic measuring device.
 There are several types of electrodes commonly used in
electrochemical applications, each with specific functions and
characteristics. Here are some of the main types of electrodes:

13. Reference Electrodes:
1. Ag/AgCl Electrode:
A widely used reference electrode with a stable and reproducible
potential.
It consists of a silver wire coated with silver chloride immersed in a
potassium chloride (KCl) solution.
2. Calomel Electrode:
Another common reference electrode, consisting of mercury covered
with a paste of mercurous chloride (Hg2Cl2) (calomel) in a potassium
chloride solution.

14. Calomel Electrode Ag/AgCl Electrode

15. Indicator Electrodes
1. Platinum Electrode:
Often used as a versatile working electrode due to its inertness
and wide potential range.
It is suitable for various electrochemical reactions.
2. Glassy Carbon Electrode:
A type of carbon electrode with a high chemical stability and wide
potential range.
It is commonly used in voltammetry and other electrochemical
techniques.

16. Glassy Carbon Electrode
Platinum Electrode

17. Ion-Selective Electrodes (ISEs)
 pH Electrode: Specifically designed to measure the hydrogen ion
concentration (pH) in solution. It typically consists of a glass membrane
sensitive to changes in pH.
 Fluoride Ion-Selective Electrode: Selectively responds to fluoride ions (F-) in
solution, allowing for the direct measurement of fluoride concentration.
 Potassium Ion-Selective Electrode: Designed to measure the concentration of
potassium ions (K+) in solution, commonly used in physiological and
environmental monitoring.

18. PHARMACEUTICAL Applications OF
POTENTIOMETRY
pH Measurement and Buffer Capacity:
 Potentiometry is widely used for pH measurement in pharmaceutical
formulations.
 pH plays a crucial role in drug stability, solubility, and bioavailability.
 Potentiometric pH measurement ensures the quality and consistency of
pharmaceutical products, including liquid formulations, creams, and
ointments.

19. Drug Dissolution Testing:
 Potentiometry is utilized in drug dissolution testing to assess the rate and
extent of drug release from solid dosage forms, such as tablets and
capsules.
 By monitoring changes in pH or ion concentration over time,
potentiometric methods provide valuable information about drug
dissolution kinetics and formulation performance.

20. Ion Concentration Measurement:
 Potentiometric ion-selective electrodes (ISEs) are used to measure ion
concentrations in pharmaceutical solutions, including electrolytes, metal
ions, and organic acids.
 These measurements are critical for monitoring electrolyte balance,
assessing drug stability, and controlling manufacturing processes.

21. Titration Assays
 Potentiometric titration methods are employed for the quantitative analysis
of pharmaceutical ingredients, including active pharmaceutical ingredients
(APIs), excipients, and impurities.
 Acid-base titrations and complexometric titrations are commonly used to
determine assay content and purity levels.

22. Content Uniformity Testing:
 Potentiometric methods are applied for content uniformity testing of solid
dosage forms, such as tablets and capsules.
 By titrating individual units with standardized solutions and measuring the
endpoint, potentiometric techniques ensure consistent drug content
throughout the batch.

23. Quality Control and Regulatory
Compliance
 Potentiometric methods are integral to quality control testing in
pharmaceutical manufacturing facilities.
 These methods provide rapid and accurate analyses of critical quality
attributes, supporting batch release and regulatory compliance.