57359 - Analysis of Medicines I (GR.B)

Learning outcomes

The aim of the course is to provide the knowledge about analytical methods (e.g. titrimetry, UV spectrophotometry) in the quantitative determination of pharmaceutical compounds. The course includes laboratory activity.

Course contents

Introduction.
Aim of the course. Introduction to quantitative analysis. The Italian Official Pharmacopoeia (F.U.) and the European Pharmacopoeia (E.P.). Safety in the laboratory environment.
Introduction to drug analysis. Solubility. Solution properties. Solubility product. Formation and dissolution of precipitates, co- and postprecipitation. Crystals, colloidal precipitates and their characteristics. Periodic system.
Introduction to volumetric analysis. Glassware and its use. Electronic balances. Concentration units. Normality, equivalents, calculus in volumetric analysis. Standard solutions. Primary standards, their properties and use.

Quantitative analysis
Acid-base titrations . Titration curves of acid and bases. Examples of acid-base titrations according to E.P.
Precipitation titrations . Precipitation titration curves. Common precipitation indicators and their use. Standard solutions used in precipitation titrations. Determination of halides by Mohr's, Volhard's and Fajans' methods. Practical aspects, limitations and applicability of the methods. Examples of precipitation titrations according to E.P.
Redox titrations. Introduction and theoretical aspects. Redox titration curves. Redox indicators and specific indicators. Permanganometry. Properties, reactions and use of permanganate solutions. Identification of the final point. Standardisation of permanganate solutions. Examples of permanganometric titrations according to E.P. Iodimetry. Preparation and use of iodine solutions. Examples of iodimetric titrations according to E.P. Iodometry. Principles, applications, properties. Use of starch water as an indicator. Examples of iodometric titrations according to E.P. Cerimetry. Properties and preparation of Ce4+ solutions. Examples of cerimetric titrations according to E.P.
Complex-formation titrations . Complex-formation and instability constants. Complexometric titration curves. Titrations employing EDTA. Conditional formation constant, a and their relationship to pH. Indicators for EDTA titrations. Direct titrations, back-titrations, displacement titrations, titrations based on indicators for an added metal ion, indirect titrations. Masking agents, masking and demasking. Analysis of complex cations mixtures. Water hardness. Examples of complexometric titrations according to E.P.
Non-aqueous titrations. Classification of the solvents used in non-aqueous titrations. Autoprotolysis constant and dielectric constant of solvents used in non-aqueous titrimetry. Apparent pH (pH*). Solvolysis reaction of weak electrolytes. Pharmacopoeial applications of non-aqueous titrations.
Potentiometry. Theory: Nernst equation; reference electrodes and working electrodes. The glass electrode for pH measurement (pH-meter); ion-sensitive electrodes in pharmaceutical analysis. Potentiometric titrations.
Biamperometry. Polarized electrodes. Diazotisation titration and Karl-Fisher titration.
Conductimetry. Theory: electrical conductivity of electrolytic solutions. Conductance cell. Specific conductivity and equivalent conductivity. Conductimetric titration techniques.
Ultraviolet and visible spectrophotometry. Keypoints. Factors governing absorption of radiation in the UV/vis region. Beer-Lambert law. Instrumentation. UV spectra of some representative drugs. Deconvolution of spectra from binary mixtures of drugs. Derivative spectrophotometry. Difference spectrophotometry. Spectrophotometric derivatization reactions: Ellman reagent; Bratton-Marshall method in analysis of sulphonamide drugs. Applications in pharmaceutical analysis.

LABORATORY
Standardization of AgNO3. Purity of NaCl.
Standardization of Na2S2O3 and of KMnO4. Purity of redox compounds according to F.U. Standardization of EDTA. Purity of ZnO.
The unknown concentration of inorganic ion solutions will be determined during the lab course.
Determination of weak acids (sulphonamide drugs) and weak bases (sodium acetate, lidocaine hydrochloride, alanine).
Potentiometric titration of phosphoric acid.
Conductimetric titration of sodium acetate.
Diazotisation titration of sulphonamide drugs (pharmacopoeial assay by biamperometric end-point detection).
Calibration of absorbance scale by using a cyanocobalamine solution (calibration graph).
UV-vis analysis of Fe(II) in tablets by complexation with o-phenantroline.

Readings/Bibliography

D. S. Hage, J. D. Carr
Chimica Analitica e Analisi Quantitativa Piccin ed. (2012)

G.C. Porretta
Analisi di preparazioni farmaceutiche - Analisi quantitativa
CISU ed.

Teaching methods

The course takes place during the second semester and is divided into two parts, 40 hours (5 ECTS Credits) of lessons and 45 hours (3 ECTS Credits) of laboratory practice; attendance is mandatory.
Volumetric analysis is explained and applied during laboratory practical for the purpose of drug purity controls and inorganic active principle determinations.

Laboratory practical is carried out individually, with a final test.

Assessment methods

The examination includes an oral examination concerning both parts of the course, aiming to verify the knowledge acquired as stated by the learning outcomes. This examination, which could also include the reading and discussion of some of the monographs of the European Pharmacopoeia and F.U.i., shall be considered positive on the basis of the correct answer to questions related to topics covered during the course.
Since the course includes practical exercises regarding the determinations described in the European Pharmacopoeia and F.U.I., the results obtained in such exercises will contribute to the definition of the final grade.

Teaching tools

Theoretical lessons will be held by using common audio-visual means.
Practical activities will be carried out in laboratories equipped with all necessary chemical reagents and analytical instrumentations.

Office hours

See the website of Roberto Mandrioli