D3 Medicines: physiochemical properties 3 Flashcards
What is partitioning?
distribution of a substance between two immiscible phases
At equilibrium is the chemical potential the same for both phases?
yes
What is the partition coefficient, when can it be defined and what does each part mean?
partition coefficient (P)= Co/Cw defined in ideal solution so dilute solutions Co = conc in organic phase Cw = conc in aqueous phase P = measure of the relative affinity of the solute for an aqueous and lipid phase at equilibrium
How is P calculated?
drug added to a separating funnel containing two immiscible liquids
flask shaken for an hour then left so two phases separate out
conc in aqueous phase determined by a suitable method
conc in organic phase determined by subtraction
What is the pharmaceutical relevance of partitioning?
explains drug partitioning between an aqueous phase and a biological lipid phase
pertaining behaviour can be used to predict biological activity of some drugs
predict unwanted pertaining into plastic materials
helps us predict shelf lives
What does Log P give an indication of?
lipophilicity of a drug
When is P only constant?
if single molecular species involved
If HA is a weakly acidic drug then what does P equal?
P = [HA]o/[HA}w
How does the P equation differ in the molecular species is more than 1?
P(app) = [HA]o/[HA]w+[A-]w
What does fraction unionised determine?
in the aqueous phase it determines the difference between P(app) & P
f(unionised)= [HA]/[HA]+[A-}
What are the two equations of partitioning of weak electrolytes?
weak acids- Log [P/P(app) -1] = pH -pKa
weak bases - Log [P/P(app) -1] = pKa - pH
Which is the organic/aqueous phase out of the lipid membrane and gastric fluid?
g.fluid - aqueous phase
L.membrane - organic phase
What needs to happen to a drug before it is passively absorbed?
needs to partition into the lipid membrane
Drug with a high log P value partition into what?
rubber and plastic containers
The site of drug action is normally in which compartment?
lipid
