Course code:
356H2
Course name:
Analytical Methods in Drug Design and Development

Academic year:

2022/2023.

Attendance requirements:

There are no requirements.

ECTS:

9

Study level:

graduate academic studies, integrated basic and graduate academic studies

Study programs:

Chemical Education: 5. year, winter semester, elective (E5AP2) course

Chemistry: 1. year, winter semester, elective (E52H2) course

Teacher:

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

Assistant:

Olivera S. Marković, Ph.D.
scientific associate, 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:

Students should become familiar with the basics in process of drug design and development as well as with methods of analysis used in the early stage of lead and drug design and development.

Outcome:

Students will be able to choose the appropriate analytical method and experimentally determine variety of physicochemical parameters of the substances.

Teaching methods:

Lectures, theoretical exercises, laboratory work, semester paper.

Extracurricular activities:

Coursebooks:

Main coursebooks:

  1. Zoran Mandić (editor): Physico-Chemical Methods in Drug Discovery and Development, IAPC Publishing, Zagreb, Croatia, 2012.
  2. Klara Valko: Physicochemical and Biomimetic Properties in Drug Discovery, John Wiley & Sons, Inc., Hoboken, New Jersey, USA, 2014.
  3. Alex Avdeef: Absorption and Drug Development. Solubility, Permeability, and Charge State, 2nd edition, John Wiley & Sons, Inc., Hoboken, New Jersey, USA, 2012.
  4. Lidija Pfendt, Dušanka Milojković-Opsenica: Jonske ravnoteže, Univerzitet u Beogradu – Hemijski fakultet, Beograd, 2014.

Supplementary coursebooks:

  • Lectures and instructions for practical laboratory work.

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

Additional material:

  Course activities and grading method

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:

  1. Acidity constants determination of polyprotic acids/bases (Active Pharmaceutical Ingredients (APIs)) by potentiometric titrations, UV/Vis and NMR spectroscopy.
  2. Determination of solubility and dissolution rate of APIs by shake-flask method.
  3. Solubility studies: tricyclic antidepressants.
  4. Study of the solubility - APIs' solid phase composition dependence by elemental and thermal analysis, and powder X-ray diffraction (PXRD).
  5. Study of APIs’ polymorphism by thermal analysis and infrared spectroscopy.
  6. Determination of Ca2+ - tetracycline complex stability constants by UV/Vis spectrophotometry and potentiometric titrations.
  7. APIs’ pH dependent lipophilicity studies by shake-flask method and HPLC.
  8. Measurements of plasma proteins - APIs binding by fluorescence spectroscopy and HPLC.
  9. NMR and UV/Vis spectroscopy studies of of biologically active molecules interactions.

Semester papers:

25 points

Oral exam:

60 points