second lec& 3rd

Physicochemical Properties of Drugs

The Effect of pH and pKa on Drug Action

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.

and Base Strength ِAcid ِ

Percentage Ionization

ExampleWhat is the ratio of ephidrine to ephedrine

HCl (pKa 9.6) in the intestinal tract at pH 8.0?

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?

pKa for the base is the pKa of its conjugate acid.

Ephedrine pKa =9.6Ammonia pKa=9.3

What is the significance of Ka and pKa values?

How can the drug pKa value be used?

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

Rules

Acid drugs – become more NON ionized in acidic pH

Basic drugs – become more NON ionized in basic pH (alkaline pH)

Acid Drug Basic DrugBasic Drug

Acid pH Environment

Basic pHBasic pH EnvironmentEnvironment

NON-ionized

NON-ionized

Rules

Acid drugs – become more NON ionized in acidic pH

Basic drugs – become more NON ionized in basic pH (alkaline pH)

Acid Drug Basic DrugBasic Drug

Acid pHAcid pH EnvironmentEnvironment

Basic pH Environment

NON-ionized

NON-ionized

IONIZED

Rules

Acid drugs – become more NON ionized in acidic pH

Basic drugs – become more NON ionized in basic pH (alkaline pH)

Acid DrugAcid Drug Basic Drug

Acid pH Environment

Basic pHBasic pH EnvironmentEnvironment

NON-ionized

NON-ionized

IONIZED

IONIZED

Rules

Hydrophilic = Ionized molecules (charged)

Lipophilic = Non-ionized molecules

) non charged(

Lipophilic molecules penetrate membranes

Hydrophilic molecules dissolve in water

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

Need three things to figure out whether drug is MAJORITY in

lipophilic or hydrophilic form

1. Whether the drug is an acid drug or a base drug.

2. The pKa of the drug (pH at which number of ionized = number of nonionized molecules)

3. pH into which the drug is going to be placed

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

IN

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

IN

WHEN GIVEN:1. Acid / Base nature of the drug

2. Drug’s pKa

3. Environmental pH drug is put into

Be able to predict whether majority of drug is in the ionizedionized form or non-ionizednon-ionized form

Be able to state whether majority of drug is in the hydrophilichydrophilic form or lipophiliclipophilic form

Be able to predict whether it can be absorbed across membrane or dissolved in water

Examples

Carboxylic Acids

Phenols

The End