Physiochemical Properties of Drugs Study Notes

1. What is the use H30+ of H+ shorthand for? 2. What is pH? - a way of expressing the hydrogen ion concentration in water 3. What does the it measures the acidity of the solution pH of a solution - it a measure of how many H+ ions are in solution measure? pH does not fully measure the strength of an acid, but the acidity of a given solution 4. How is pKa more - it tells us a certain molecule will react when in a solution specific than pH? that is at a specific pH 5. What is the equation to find out the fraction of unionised drugs in acidic drugs? 6. What is the equation to find out the fraction of unionised drugs in basic drugs? 7. In the Ka equa- - Ka is large tion, what does it - acid is strong mean if the numerator is larger than the denominator? 8. What is the acid acid colour = red and base colour base colour = yellow orange 1 / 10 of methyl orange? 9. What is the acid acid colour = red and base colour base colour = yellow of methyl red? 10. What is the acid acid colour = red and base colour base colour = blue of litmus? 11. What is the acid acid colour = yellow and base colour base colour = blue of thymol blue? 12. What is the acid acid colour = yellow and base colour base colour = lilac of alizarin yellow? 13. What is the Arrhenius definition of an acid? a substance that contains hydrogen and dissociates in water to yield a hydronium ion 14. What is the Arrhenius definition of a base? a substance that contains the hydroxyl group and dissociates in water to yield a hydroxyl ion (OH-) 15. What is the aqueous solutions Arrhenius definition restricted to? 16. What is the Bron- tendency to lose a proton sted-Lowry definition of an acid? 17. What is the bron- tendency to accept a proton sted-lowry definition of a base? 2 / 10 18. What is an the ability to act as both an acid and a base amphoteric compound? 19. What is the Lewis An electron pair acceptor definition of an acid? 20. What is the lewis an electron pair donor definition of a base? 21. What are the - sour taste characteristics of - react with metals acids? - contain hydrogen - poisonous + corrosive to skin 22. Describe strong dissociate completely to give off many H+ ions acids: 23. Describe weak acids: dissociate partially to give off some H+ ions 24. What are the - taste bitter characteristics of - feel slippery bases? - contain hydroxide ions - poisonous + corrosive to skin 25. Give examples of - sulphuric acid strong acids: - HCl - nitric acid 26. Give examples of - lithium hydroxide strong bases: - sodium hydroxide - potassium hydroxide 27. Give examples of - acetic acid weak acids: - carbonic acid 3 / 10 28. Give examples of hydroxides of group 1 and 2 metals are strong weak bases: - all others are weak 29. What does Ka measure? the position of equilibrium 30. Describe the rela- the further the equilibrium lies to the right, the more comtionship between pletely the acid is ionised equilibrium and ionisation: 31. What can Ka also pKa = -log(Ka) be expressed as? 32. What does a larg- - lower Ka er value of pKa - weaker acid mean? 33. How dissociated 50% dissociated will the acid be when the pH of a solution is equal to the pKa? 34. What does it pH is higher than pKa mean if the acid is more than 50% dissociated? 35. What is a buffer? a solution with a known pH, which resists changes in pH 36. What are buffers weak acids and their salts composed of? weak bases and their salts 37. When does opti- at a pH that is between pKa +1 and pKa -1 mal buffering occur? 38. What is the pH = pKa + log([A-]/[HA]) Henderson-Has4 / 10 slebalch equation? 39. Why is a drugs - A drug must be dissolved in water before it is able to cross ability to disbiological membranes, reach its pharmacological target + solve in waelicit a therapeutic effect ter a fundamental physicochemical property? 40. What is a solution? 1 phase system which consists of solute molecules dissolved within a solvent vehicle 41. What is a solute? a substance which is dissolved in solution 42. What is a solvent? a substance that is used to dissolve a solute 43. What is dissolu- the preparation of a solution by mixing together solute + tion? solvent until a homogenous liquid is obtained 44. What is a saturat- Is a solution in which the maximum amount of solute has ed solution? been dissolved in the solvent at a given temperature 45. What is an unsat- The dissolved solute is at a concentration below that necurated solution? essary for complete saturation of the solvent. 46. What is a suThe solute exists in the solution above its normal solubility persaturated so- limit lution? - can be obtained by altering the temperature, volume / pressure 47. What is a crystalline solid? a solid whose constituent atoms, molecules/ions are arranged in an ordered 3D pattern 48. What is an amor- - lacks the ordered characteristics of a crystal - it does phous solid? not have a regular, repeating atomic arrangement like the crystalline solid 5 / 10 49. What is maxiThe max amount of a solute that can be dissolved in a solmum solubility? vent under specific conditions ( at a defined temperature, pressure, pH) 50. What is hydrophilicity? the affinity of a compound to water 51. What is hydrophobicity? repulsion of a compound from water 52. What increases polar functional groups water solubility? 53. What is the rela- compounds with high melting points usually show poor tionship between water solubility + vs melting point and water solubility? 54. What are colliga- A property of a solution that depends on the amount of tive properties? solute present and not upon the nature of the solute itself 55. What are some - lowing of vapour pressure (the addition of non-volatile colligative prop- solute reduces the vapour pressure of the solution) erties? - elevation of boiling point & depression of freezing point ( the addition of the solute stabilises the solvent in the liquid phase = meaning it has less tendency to move to the gas/solid phase ) 56. Describe how liq- the tonicity must be equivalent to that of blood uid preparations coming into contact with the body are altered to prevent movement of water: 57. Define osmotic pressure: the pressure needed to stop the movement of water 6 / 10 58. Describe the ba- 1) a solute molecule is removed from its bulk structure sic solubilisation 2) a cavity for this molecule is created in the solvent process: 3) the solute molecule inserts itself into the cavity + interacts with the solvent molecules forming bonds 59. Why do crysthey have strong intermolecular bonds tal structures require more energy to break apart than amorphous solids? 60. Compare the melting points and water solubilities of crystalline and amorphous solids? - crystals display higher melting points and lower solubility than amorphous solids - crystal structures which are highly ordered have stronger intermolecular bonds 61. Describe the 1) add a third substance to an oil-water system process of parti- 2_ it will distribute itself throughout the 2 layers tioning: 3) if the substance is hydrophobic it will conc/within the oil non-polar phase / if hydrophilic it will conc. in the aq phase 62. What is the equa- P = [non-polar phase / polar phase] tion for partition coefficient? 63. What does the only valid for solutes that are not ionised at the pH studies solute have to be in order for a simple model of partitioning to be valid? 64. Why is the pH of It will dictate whether a compound will be ionised or not, a solution impor- hence it's affinity for an aqueous/ oily phase. tant when measuring a solute partitioning? 7 / 10 65. Where are weak- stomach ly acidic drugs more likely to be absorbed? 66. Where are weakly small intestine basic drugs more likely to be absorbed? 67. What is log P? - a measure of a compounds hydrophilic + hydrophobic nature - provides insights into the bioavailability of a drug where it enters the body 68. What happens It will show excellent water solubility, but it will not be able when a drug is to cross biological membranes since they have hydrophotoo hydrophilic? bic characteristics. 69. What happens if would be poorly water soluble and would enter, but not a drug is too hy- leave cell membranes drophobic? 70. Describe the shake-flask method of Log P determination: - a volume of octanol + water is left to equilibrate - a substance is added + shaken and left to settle - the conc. of the substance in 1 solvent is then found, often via UV spectroscopy 71. Why is octanol used in the shake-flask method? because the structure resembles the amphiphilic form of a phospholipid 72. Why is it imDrug must be able to partition into the lipid bilayer + not portant that a partition back out again drug has both hydrophobic and hydrophilic properties? 8 / 10 73. What program is Estimation program interface (EPI) used to predict LogP values? 74. How does temperature affect solubility? As temperature increases, solubility increases - Kinetic energy increases = causing solute dispersion to increase, exposing solute to fresh solvent faster 75. How does pres- Increasing pressure has no effect on solubility sure affect solu- - has no effect on gases dissolved = increases their solubility? bility as they form supersaturated solutions. 76. What does Lipin- that problems with absorption can be prevented if 2 of 4 ski's rule state? rules are avoided: - MV < less than 500 - partition coefficient (Log P)< 5 - no. of H-bond donors < 5 - no. of H-bond acceptors <10 77. What are the 7 molecular structures and properties that affect solubility? 1) melting point = compounds with low melting point show good water solubility 2) molecular shape and symmetry = unsymmetrical molecules - symmetrical, flat molecules pack tightly together with stronger intermolecular forces - resulting in higher melting point 3) increasing molecular weight = results in a decrease in water solubility 4) H-bonding ability = addition of H-bonds usually increased solubility 5) Polar (ionisable) functional groups = increased water solubility 6) Non-polar functional groups = decrease aqueous solubility as they increase the hydrophobic character 9 / 10 7) pH = is important as it determines the proportion of an ionisable drug that is charged, more soluble as pH increases 78. What is intrinsic the solubility of the free (unionised) solute solubility? 10 / 10