Partitioning

Question 1

Definition

Partitioning

Answer 1

• Partitioning is the distribution of a substance
  between two immiscible phases

Question 2

Steps of partitioning

Answer 2

• Immiscible liquids added to
  separating funnel
• Drug under investigation added to
  the mixture
• Separating funnel shaken (open tap
  regularly to release pressure build-
  up)
• Immiscible phases separated and
  concentration of drug in each liquid
  determined
• Partition coefficient is determined
  from these values

Question 3

partition coefficient

Answer 3

• Conc of organic phase/Conc of aqueous phase

Question 4

What is the partion coefficient a measure of

Answer 4

• Relative affinity of the solute for an aqueous and a lipid phase at equilibrium –it will be constant
• Dilute solutions

Question 5

Log P

Answer 5

• The range of the partition coefficients
  of common drugs is quite large
• Often log10 P is used
• Log P gives an indication of the lipophilicity of a drug
• Caffeine - hydrophilic to hydrocortisone hydrophobic

Question 6

Partitioning of weak acids & bases

Answer 6

• If the pH is changed and ionisation occurs in the aqueous phase, then there will be two species present
• Papp = [HA]o /[HA]w + [A]-w
• Degree of ionisation (hence [HA]w) is
  controlled by pH, so the pH will also alter Papp

Question 7

fraction unionised

Answer 7

• Aqueous phase determines the difference between Papp and P
• [HA]/[HA] + [A-]

Question 8

Weak acid partition equation

Answer 8

Log (P/Papp - 1) = pH - pKa

Question 9

Weak bases

Answer 9

Log (P/Papp - 1) = pKa - pH

Question 10

Pharmacutical requirement for partitioning

Answer 10

need to pass several lipophilic barriers
intestinal membrane, cell membranes, blood-brain barrier before they can exert an affect

Question 11

Aqueous solubility

Answer 11

• Important as the drug molecule is typically required to be in solution for absorption to occur

Question 12

Why is log P used?

Answer 12

• Used to measure the balanced hydrophilic-lipophilic
  properties are required

Question 13

Preservatives

Answer 13

• Used in oral liquid formulations – this can present challenges with emulsions / creams
• Conc of aqueous phase may be lower that we had calculated

Question 14

High log P

Answer 14

• Readily partition into rubber or plastic substances, e.g. containers, stoppers, septa, infusion bags/lines
• Many formulations are affected
• GTN has a volatile drug with a relatively high
  log P of 2.154 will partition from tablets into plastic
  packages
• Difficult storage of lipophilic drugs

Question 15

MAC

Answer 15

• Minimum alveolar concentration (the lower this is the more potent the anaesthetic is)
• Linear relationship on log scale compared to partition coefficient