Analytical Methods in Drug Design and Development   (356H2)

Academic year:

2025/2026.

Attendance requirements:

There are no requirements.

ECTS:

9

Study level:

Study programs:

Teacher:

Tatjana Ž. Verbić, Ph.D.
associate professor, Faculty of Chemistry, Studentski trg 12-16, Beograd

Assistant:

Mladen M. Đurđević
junior research assistant, Institute of Chemistry, Technology and Metallurgy, Njegoševa 12, Beograd

Hours of instruction:

Weekly: four hours of lectures + two hours of exercises + three hours of labwork (4+2+3)

Goals:

Physicochemical characterization, the study of different types of ionic equilibria and interactions of (potentially) biologically active substances are key steps in the early phase of drug development and in predicting the pharmacokinetic and pharmacodynamic properties of compounds. The importance of these studies has been recognized after it was estimated that approximately one-third of substances rejected during preclinical testing were rejected due to poor ADME (absorption, distribution, metabolism, excretion) properties, which largely depend on the physicochemical characteristics of the substances.

The aim of this course is to introduce the process of drug design and development and the analytical methods used in the early phase of drug development, with a particular focus on determination of physicochemical parameters (acidity constants, intrinsic solubility and solubility product, partition and distribution coefficient, and permeability) of biologically active compounds, as well as studying their various equilibria and biological interactions. The course also focuses on the definition, adjustment, and maintenance of experimental conditions under which measurements are conducted, calibration of analytical instruments, and the interpretation and understanding of the obtained results within the broader framework of drug design and development.

Outcome:

Upon successful completion of the course, the student will be able to: understand the process of drug design and development, design an experiment and select appropriate methods for the experimental determination of various physicochemical parameters of substances, process and analyze experimental data and critically evaluate the obtained results, interpret the results within the context of the drug design and development process, apply the acquired knowledge to work in laboratories engaged in analytical, pharmaceutical, or medicinal chemistry and effectively integrate into a multidisciplinary team working in the field of drug design and development.

Teaching methods:

Lectures, theoretical exercises, laboratory work, semester paper.

Extracurricular activities:

—

Coursebooks:

Main coursebooks:

1. Tatjana Verbić, Olivera Marković, Miloš Pešić: Analitičke metode u dizajnu i razvoju lekova, Univerzitet u Beogradu - Hemijski fakultet, Beograd, 2025. ISBN: 978-86-7220-132-1

Supplementary coursebooks:

1. Lidija Pfendt, Dušanka Milojković-Opsenica: Jonske ravnoteže, Univerzitet u Beogradu - Hemijski fakultet, Beograd, 2014.
2. Lectures and instructions for practical laboratory work.

Lectures and manuals for lab work will be provided during the course through Faculty network.

Additional material:

—

Lectures:

0 points (4 hours a week)

Syllabus:

1. Thermodynamics of chemical equilibria.
2. Equilibrium constants: general methods for experimental determination and calculation.
3. Introduction to drug design and development process.
4. Physicochemical compound characterization: basic ADME properties.
5. Acid-base equilibria. Acidity constants: importance and methods for experimental determination.
6. Physiologically important buffers.
7. Solubility and dissolution rate under physiological conditions. Importance and methods for experimental determination.
8. Application of thermal analysis in solubility studies.
9. Experimental methods for active pharmaceutical ingredient (API) solubilization.
10. Complex compounds equilibria in solutions. Importance and methods for experimental stability constants determination.
11. Lipophilicity. Importance and methods for experimental determination.
12. Permeability. Importance and methods for experimental determination.
13. Experimental methods for API – plasma protein interaction studies.
14. Application of chromatographic techniques for compound ADME properties studies.
15. Application of NMR and IR spectroscopy in drug design and development.

Exercises:

0 points (2 hours a week)

Syllabus:

The terms of theoretical exercises are combined with laboratory exercises. During the long-lasting experiments attention will be paid to particular case studies from the field of lead optimization and drug design and development. Case studies will be related to the on-going thematic unit addressed during lectures and laboratory exercises.

Labwork:

15 points (3 hours a week)

Syllabus:

The laboratory work is tailored to each individual student, based on the 'case study' principle, and covers the following thematic units:

1. Determination of API (Active Pharmaceutical Ingredients) solubility by shake-flask method.
2. Determination of API solubility in biorelevant media.
3. Study of the supersolubility of tricyclic antidepressants using the conductometric titration method.
4. pDISOL-X program and "case studies": solubility profiles, precipitate analysis using TGA and DSC methods, study of polymorphism by thermal analysis and IR spectroscopy, investigation of interactions of biologically active molecules using UV-Vis and NMR spectroscopy.
5. Study of the dissolution rate of active pharmaceutical ingredients from pharmaceutical dosage forms (tablets and capsules).
6. Determination of acid constants of polyprotic acids/bases - active pharmaceutical ingredients – using potentiometry, spectrophotometry, and NMR spectroscopy.
7. Determination of lipophilicity of active pharmaceutical ingredients depending on pH using the shake-flask method, potentiometry, and HPLC.
8. Spectrophotometric determination of stoichiometry and stability constants of API-β-cyclodextrin complexes; photodegradation of API-β-cyclodextrin complexes complexes.
9. Measurements of plasma proteins - APIs binding by fluorescence spectroscopy and HPLC.
10. Determination of Ca²⁺-tetracycline complex stability constants using UV/Vis spectrophotometry and potentiometric titration methods.

Semester papers:

25 points

Oral exam:

60 points