Physicochemical Properties Study Notes

31/10/2023 * Physicochemical Properties 4PY019 Dr Mark Hewitt 1 *Overview * By the end of this session: * Understand what is meant by “physicochemical property” * Be able to discuss the types of physicochemical properties with examples * Appreciate why these properties are important in the area of pharmaceutics (and beyond) 2 1 31/10/2023 * What is a Physicochemical Property? “Any physical or chemical characteristic/property attributed to a defined compound” A Person A Chemical We can identify a person by their face, voice, height, fingerprints, DNA, etc. We can ID a chemical by looking at its physicochemical properties * Every chemical has a unique set of physicochemical properties * These properties are a consequence of chemical structure 3 * Does Structure Really Matter? * Take these two people for example: * Based on their structure, do you think they will have the same properties / capabilities? * Of course not! * The same is true with chemical structures * Different shapes, sizes, functional groups, etc. displaying different properties 4 2 31/10/2023 * There are 2 Types of Properties * The clue is in the name! Physical Properties Chemical Properties State (solid, liquid, gas) pH, pKa Colour Reactivity Melting/Boiling point Heat of combustion Solubility/Hydrophobicity Half life Density Stability/Degradation IR spectrum Do not change the chemical composition Those that are only evident when a change occurs 5 * EXAMPLE: The Physicochemical Properties of…..? Appearance: Odourless, colourless to white, crystalline powder. Develops a vinegar-like odour on contact with moisture Taste: Slightly bitter Stability: Stable, keep dry Melting point: 138-140oC Boiling point: Decomposes at 140oC Flash point: 250oC Solubility: Water 3.3mg/ml pKa: 3.5 Log P: 1.19 Heat of combustion: -3927 kJ/mol Refractive index: 1.5623 6 3 31/10/2023 * IR Spectra for Aspirin * Unique chemical structure = unique IR fingerprint *Spectra obtained from Sigmaaldrich.com 7 * How Can We Obtain These Properties? * Visually – Phase, colour, etc. * Experimentally – MPt, BPt, pKa, simple functional group tests, IR/UV/NMR spectrophotometry * Reference Sources - Books (Merck Index, Martindale..) - Online resources (ChemSpider) * Predict – Using specialist software 8 4 31/10/2023 * Importance of Phys-chem Properties (1) * Physicochemical properties can be used to identify unknown compounds: * Impurities * Reaction products * Within Manufacturing Quality Control (QC) * Confirm identity of product * Assess purity 9 * Importance of Phys-chem Properties (2) * The physicochemical properties of a compound will determine binding to a target receptor 10 5 31/10/2023 A drug must be able to do MORE than just bind to a receptor! 11 * Before We Even Think About Receptors… An oral drug must be able to: 1. Dissolve (3.3mg/ml) 2. Survive pH changes (1.5-8) 3. Survive intestinal bacteria 4. Cross membranes (Log P = 1.19) 5. Avoid extensive first-pass metabolism 6. Avoid active transport to bile 7. Avoid rapid excretion by kidneys 8. Partition into target organ 9. Avoid undesired partitioning (e.g. brain, foetus) 10. Be cleared from the body (prevent overdose) 12 6 31/10/2023 * RECAP: Importance of Physicochemical Properties * The physicochemical properties of a compound dictate a drugs activity: * Solubility and partitioning (A & D) * Metabolism (M) * Excretion (E) * Stability / reactivity * Toxicity (T) * Binding to receptors (potency) * Etc… 13 * Non-Clinical Considerations * The physicochemical properties of a compound also has implications for handling and storage: * Considerations during drug manufacture * Design of drug packaging * Etc. * Hydrolysis of Aspirin * Solid aspirin is hygroscopic (absorbs moisture) 14 7 31/10/2023 * STUDY PACK * Physicochemical Properties of Drugs * Is available in the “Physicochemical Properties” folder * TBL on this pack NEXT week 15 * A Brief Tour * Solubility * Why is it important? * Terminology * The solubilisation process * Solvents (polar and non-polar) * The structure of water * Properties of solutions * Colligative properties * Osmosis * Tonicity * Hydrophilicity/hydrophobicity * Partitioning * Partition coefficient (log P) * Distribution coefficient (log D) 16 8 31/10/2023 *Any Questions? 17 9