D3 Medicines: physiochemical properties 3 Flashcards
What is partitioning?
The distribution (or moving) of a substance between two immiscible phases
When is the chemical potential equal in both phases?
At equilibrium
What is the partition coefficient?
Partition coefficient (P) = Co / Cw
Where Co is the concentration in the organic phase
Cw is the concentration in the aqueous phase
What does P measure?
The relative affinity of the solute for an aqueous and a lipid phase at eqm (it will be constant)
What is log P?
Range of P values often large, log values allow us to compare more easily
Log P gives an indication of the lipophilicity of a drug
When is P constant?
If only a single molecular species is involved
Drugs are often weak electrolytes and therefore exist in more than one molecular species. How does this affect P?
P must be adjusted in order to allow for ionisation. “P app” is the apparent partition coefficient and takes into account the consequences of ionisation
What is the apparent partition coefficient (P app)?
[HA]o / [HA]w + [A-]w
What is the fraction unionised?
The fraction unionised in the aqueous phase determines the difference between P app and P
P app = P x f unionised
What is the main site of absorption for most drugs?
GI Tract
For a drug to be passively absorbed what must happen?
It must partition into the lipid membrane
Diffusion across the membrane is governed by which law?
Fick’s First Law (contains P)
Why is partitioning important for drug delivery?
Drugs need to partition between lipid phases and also aqueous phases. Lipid cell membranes
Aqueous intracellular spaces
As a result of this fact, most successful drugs have an intermediate P value
What are the problems associated with drugs that have a high P value?
Readily partition into rubber or plastic containers making it difficult to store highly lipophillic drugs and also to administer through plastic tubing e.g. IV
