Solubility and partitioning

Question 1

Name 2 barriers a drug may have to pass in order to reach its site of action

Answer 1

GIT (gastrointestinal tract)
BBB (blood-brain barrier)
Both pass lipid cell membranes

Question 2

What will happen in excess of an organic compound is added to a mixture of two immiscible liquids?

Answer 2

It will partition itself between the two liquids so that each becomes saturated
However, if the amount of compound is not sufficient to saturate the solutions, it will be distributed between the two immiscible liquids according to the definite concentration ratio:
Corg(organic phase) Caq(aqueous phase)

Question 3

Define the partition coefficient (P)

Answer 3

The ratio of concentration of compound in the organic phase to the concentration of compound in the aqueous phase at equilibrium:
P=Corg/Caq
where
Corg= concentration of drug in the organic lyaer
Caq= concentration of drug in the aqueous layer

Question 4

Define the true partition coefficient

Answer 4

the partition coefficient of unionised drug

Question 5

If Ptrue>1 then..

Answer 5

Corg>Caq and the compound is hydrophobic

Question 6

If Ptrue<1 then..

Answer 6

Corg

Question 7

LogP=

Answer 7

Log10(partition coefficient)

Question 8

If LogP=1 then what is P equal to and what is the ratio of solubility like?

Answer 8

P=10
Corg:Caq = 10:1
i.e.
the solubility in the organic phase is 10 times higher than that of the aqueous phase

Question 9

If LogP=0 what is P equal to and what is the ratio of solubility like?

Answer 9

P=0
Corg:Caq= 1:1
the compound has equal solubility in the organic and aqueous phases

Question 10

if LogP=-1 what is P equal to and what is the ratio of the solubility like?

Answer 10

P=0.1
Corg:Caq=1:10
i.e. the solubility in the aqueous phase is 10 times higher than that of the organic phase

Question 11

What can the partition coefficient be used to predict about the drug?

Answer 11

absorption, distribution and elimination of the drug
in medicinal chemistry, structure-activity relations use maths to relate the drug’s biological activity to its physical and chemical properties

Question 12

Define chemical polarity

Answer 12

describes how equally bonding electrons are shared between atoms
it is a physical property of compounds that affects other physical properties, e.g. solubility

Question 13

What do Hansch -Fujita parameters describe?

Answer 13

symbol: π

describe the contribution of various functional groups to the hydrophobicity of a compounds

Question 14

A predominance in +π groups will result in what property?

Answer 14

Hydrophobicity of a compound and an increase in the partition coefficient. Compound more able to cross lipid membranes

Question 15

Name 3 hydrophobic functional groups where π is positive

Answer 15

aromatic hydrocarbons
aliphatic hydrocarbons
halogens

Question 16

Name 5 hydrophilic functional groups where π is negative

Answer 16

• Hydroxyl group
• carboxyl
• amines
• ether
• amide

Question 17

A predominance in -π groups will result in what property?

Answer 17

Decrease in partition coefficient
more hydrophilic
difficult to pass through lipid membranes

Question 18

The partition coefficient can be used with the pKa to…

Answer 18

predict the distribution of a drug compound in a biological system

Question 19

If the partition coefficient is ionised, it will greatly alter the partitioning of the compound… why?

Answer 19

because the permeability of an unionised form of a drug across a phospholipid bilayer by passive diffusion is about 10^8 higher than that of the ionised form
therefore we assume only the unionised drug will partition into the organic layer

Question 20

the concentration of compound passing through a membrane depends on the %…

Answer 20

unionised

Question 21

the % unionised of a compound depends on..

Answer 21

the pKa and pH of the solution

Question 22

For neutral compound e.g. chlorobenzene,

how does the partition coefficient change with pH?

Answer 22

Same at any pH

Question 23

For weak acids and bases, does the partition coefficient change with pH?

Answer 23

yes, because pH alters compounds ionisation and the true partition coefficient includes ionised molecules

Question 24

equation

P(apparent)=

Answer 24

P(true) x f(unionised)

where f= fraction of drug unionised at a certain pH

Question 25

%unionised=

Answer 25

100
____________
1+antilog(pka-ph)

Question 26

Why do patients taking antihistamine drugs for travel sickness need to take their medication at least 1 hour before travelling?

Answer 26

Drug is only absorbed in the small intestine, hence delay of onset whilst drug passes through stomach

Question 27

Patient has taken an overdose of an acidic drug, what is the treatment?

Answer 27

Forced base diuresis
acidic drugs best reabsorbed by acidic urine
basify urine to stop this from happening - add sodium bicarbonate
this will reduce the amount of acidic drug reabsorbed
thus more rapid clearance of acidic drug

Question 28

Patient has taken an overdose of a basic drug, what is the treatment,

Answer 28

forced acid diuresis
basic drugs best reabsorbed by basic urine
acidify the urine to stop this from happening
add ammonium chloride or ascorbic acid (vitamin C)
this will reduce the amount of basic drug reabsorbed and hence there will be more rapid clearance of the basic drug