In the ever-demanding world of pharmaceutical quality control, accuracy isn’t just a virtue—it’s a necessity. Beyond acid-base and redox reactions lies a fascinating set of analytical tools that ensure drug safety and reliability. Unit 3 of Pharmaceutical Analysis explores precipitation titrations, complexometric analysis, gravimetric methods, and diazotisation titrations—all of which continue to be indispensable in drug research and testing.
Download UNIT 3 – The Science of Advanced Titrations – From Precipitates to Complexes Notes
Get simplified revision notes for this unit:
Download Unit 3 Notes PDF
Precipitation Titrations: The Power of Insoluble Compounds
Precipitation titrations are based on the formation of a sparingly soluble precipitate during a chemical reaction. These methods are especially useful for halide ion estimation, with silver nitrate often serving as the key titrant.
Mohr’s Method
Mohr’s method employs silver nitrate as the titrant and potassium chromate as the indicator. When silver ions completely precipitate chloride ions as silver chloride, any excess reacts with chromate to produce a brick-red precipitate of silver chromate, signaling the endpoint.
Volhard’s Method
This method works in acidic medium, where chloride is precipitated with excess silver nitrate. The unreacted silver is then titrated back with thiocyanate solution, using ferric ion as an indicator. The deep red complex formed indicates the completion of the reaction.
Modified Volhard’s Method
A practical twist to the classical Volhard technique, this variation involves filtering off the precipitate before back-titration, improving accuracy in challenging samples.
Fajans Method
Here, adsorption indicators such as fluorescein are used. The endpoint is detected by a change in the surface adsorption layer of the precipitate—an elegant method requiring precision in observation.
Application: Estimation of Sodium Chloride
All these methods find real-world pharmaceutical relevance in the estimation of sodium chloride, an essential component in many drug formulations. Ensuring correct salt concentration is vital for both therapeutic effectiveness and patient safety.
Complexometric Titrations: Unlocking the World of Metal Ions
Complexometric titrations work on the principle of forming stable complexes between metal ions and chelating agents. The most widely used reagent here is EDTA (Ethylenediaminetetraacetic acid).
Classification of Complexometric Methods
These titrations are broadly classified based on the reaction conditions:
Direct titration: Metal ion titrated directly with EDTA.
Back titration: Excess EDTA is added and the unreacted portion titrated with a standard solution of a metal ion.
Replacement titration: One metal is displaced by another, followed by titration.
Indirect titration: Metal ions estimated via precipitation, followed by EDTA analysis.
Metal Ion Indicators
Indicators like Eriochrome Black T and Murexide are used to detect endpoints, changing color when metal ions are fully complexed with EDTA.
Masking and Demasking Agents
In multi-ion systems, selectivity is achieved using masking agents (which bind interfering ions) and demasking agents (which release them again for analysis).
Applications in Pharmaceuticals
Magnesium Sulphate Estimation: By titrating magnesium ions with EDTA using Eriochrome Black T.
Calcium Gluconate Estimation: Calcium content is determined similarly, ensuring precise dosage in supplements and injectables.
Gravimetric Analysis: Weighing Chemistry’s Accuracy
While titrations depend on volume measurements, gravimetry relies on weight as the ultimate measure of accuracy. This classical method involves converting the analyte into a pure, stable, and easily weighable precipitate.
Steps in Gravimetric Analysis
Precipitation: Formation of an insoluble compound.
Digestion: Improving particle size and purity.
Filtration and Washing: Removing impurities.
Drying or Ignition: Obtaining a stable form for weighing.
Weighing: Final determination of the analyte mass.
Purity Concerns
Co-precipitation: Unwanted impurities carried down with the precipitate.
Post-precipitation: Formation of secondary crystals on standing.
Analysts must carefully control these factors to maintain accuracy.
Application: Estimation of Barium Sulphate
A classic example is the gravimetric determination of barium by precipitation as barium sulphate, a highly insoluble and stable salt.
Diazotisation Titrations: Color Meets Chemistry
Diazotisation titration is a unique analytical tool where aromatic amines react with nitrous acid to form diazonium salts.
Principle and Methods
Nitrous acid, generated in situ from sodium nitrite and hydrochloric acid, reacts quantitatively with primary aromatic amines. The endpoint is typically detected using indicators such as starch-iodide paper or sulfanilic acid.
Applications in Pharmacy
Diazotisation titrations are widely used in the estimation of drugs like sulphonamides, where precise determination of amine groups is critical for drug quality.