The document discusses physicochemical properties of drugs, specifically how the acid-base properties and pKa values of drugs influence their distribution and partitioning in the body. It provides definitions of acid-base concepts like pH, pKa, and the Arrhenius definition of acids and bases. It also explains how the percentage of ionization of acid and base drugs depends on the environmental pH relative to the drug's pKa. The ionization state determines if a drug is hydrophilic and water-soluble or lipophilic and able to pass through cell membranes. Rules are provided about how acid and base drugs behave in different pH environments and whether they will be ionized or non-ionized.

2. Physicochemical Properties of Drugs The Effect of pH and pKa on Drug Action

3. most drugs are small organic molecules that behave in solution as either weak acids or weak bases. Acid-Base properties of drugs greatly influences their biodistribution and partitioning characteristics. What does it mean to say that a certain molecule is an acid or base? Arrhenius definition.

11. and Base Strength ِ Acid ِ

17. Percentage Ionization

19. Example What is the ratio of ephidrine to ephedrine HCl (pKa 9.6) in the intestinal tract at pH 8.0?

21. What is the percentage ionization of: 1. ephedrine HCl (pKa 9.6) and 2. indomethacin (pKa 4.5) in an intestinal tract with pH 8?

22. pKa for the base is the pKa of its conjugate acid. Ephedrine pKa =9.6 Ammonia pKa=9.3

23. What is the significance of Ka and pKa values?

26. How can the drug pKa value be used?

27. Rules Acid drugs – become more NON ionized in acidic pH Basic drugs – become more NON ionized in basic pH (alkaline pH) Acid Drug Basic Drug Acid pH Environment Basic pH Environment

28. Rules Acid drugs – become more NON ionized in acidic pH Basic drugs – become more NON ionized in basic pH (alkaline pH) Acid Drug Basic Drug Acid pH Environment Basic pH Environment NON-ionized NON-ionized

29. Rules Acid drugs – become more NON ionized in acidic pH Basic drugs – become more NON ionized in basic pH (alkaline pH) Acid Drug Basic Drug Acid pH Environment Basic pH Environment NON-ionized NON-ionized IONIZED

30. Rules Acid drugs – become more NON ionized in acidic pH Basic drugs – become more NON ionized in basic pH (alkaline pH) Acid Drug Basic Drug Acid pH Environment Basic pH Environment NON-ionized NON-ionized IONIZED IONIZED

31. Rules Hydrophilic = Ionized molecules (charged) Lipophilic = Non-ionized molecules (non charged) Lipophilic molecules penetrate membranes Hydrophilic molecules dissolve in water

32. Depending if a molecule is ionized or not determines if it can pass through a cell membrane C E L L M E M B R A N E Ionized Molecule Non-Ionized Molecule

33. Need three things to figure out whether drug is MAJORITY in lipophilic or hydrophilic form Whether the drug is an acid drug or a base drug. The pKa of the drug (pH at which number of ionized = number of nonionized molecules) pH into which the drug is going to be placed

34. Acid Drug = Non ionized molecules = Ionized molecules Acid drugs – become more NON ionized in acidic pH pH 2 N I pH 6 N I pH 9 I pH 8 I N

35. Basic Drug = Non ionized molecules = Ionized molecules Basic drugs – become more NON ionized in basic pH pH 9 N I pH 8 N I pH 2 I pH 6 I N

36. WHEN GIVEN: Acid / Base nature of the drug Drug’s pKa Environmental pH drug is put into Be able to predict whether majority of drug is in the ionized form or non-ionized form Be able to state whether majority of drug is in the hydrophilic form or lipophilic form Be able to predict whether it can be absorbed across membrane or dissolved in water

37. Examples

38. Carboxylic Acids

40. Phenols

43. The End