Crystallization and polymoprhic forms of drugs

elective courses

The lecture is intended for a wide range of listeners interested in solid state chemistry, the process of formulation of drugs from active pharmaceutical ingredients (APIs), and crystallography. Listeners should know the basics of mathematics and crystallography. Lecture intended for students in the fields of Chemistry II degree, Medical Chemistry II degree, Nanostructure Engineering.

Blended learning

During the lecture, students will learn the purification and crystallization methods used in organic chemistry and the pharmaceutical industry from the practical and theoretical point of view. Particular emphasis will be placed on the stability of polymorphic forms, their characterization and the prediction of thermodynamic properties of crystal forms.

Topics discussed in the lecture:

1. Definition of the solidstates and their various forms (crystals, powders, amorphous). Types of crystals: cocrystals, salts, polymorphs, hydrates and salts. Physico-chemical properties of solid state (mechanical properties, solubility, compressibility, particle size distribution, plasticity, stability, reactivity). Solid state characterization methods (XRD, NMR, DSC, TGA, microscopy)

2. The difference between the active pharmaceutical ingredient and the drug.

3. Theory of nucleation and crystal growth in kinetic and thermodynamic terms

4. Methods of crystallization in the solution (evaporation, cooling, vapor diffusion, solvent layering), in gels, polymers, slurry. Crystallization from solid state, melts and vapor.

5. Crystallization as a method of separating optically active compounds

6. Predicting crystal morphology: non-mechanical models (BFDH model, attachment energy model) and mechanical models

7. Polymorphism in the pharmaceutical industry

8. Methods of characterization of polymorphic forms. Solid characterization methods (XRD, NMR, DSC, TGA, microscopy, IR spectroscopy, Raman, melting point)

9. Methods of selective crystallization of polymorphic forms

10. Determination of the mutual stability of polymorphic forms

11. Essential drugs (pharmaceuticals, medicines) that have different polymorphic forms (Zantac, Aspirin, Ritonavir)

12. From idea to drug. Development of a drug from an active - chemistry, production and control. Production of tablets, suspensions, inhalers.

Polymorphism in Molecular Crystals, Joel Bernstein, Oxford University Press

Crystal Growth For Beginners: Fundamentals Of Nucleation, Crystal

Growth And Epitaxy Fundamentals of Nucleation, Crystal Growth and

Epitaxy, Ivan V Markov, World Scientific Publishing Company

After the lecture, students know the essential physicochemical properties of solids, their different forms, characteristic properties and applications. They understand the difference in the design, development, production process depending on the solid form of API and know the research methods used in the purification and formulation of biologically active compounds, and how polymorphic forms are used in the pharmaceutical industry.

Presentation about the publication concerning one of the topic discussed in the lecture