Pharmaceutics Flashcards
Describe the dissolution process.
Dosage form in solution disintegrates into granules.
These then breakdown further into fine particles which increases surface area.
This allows for dissolution so drug can be solubilised in order for it to be absorbed.
Throughout the GI tract, pH changes and so a soluble drug may become insoluble and precipitate out or form complexes into finer particles
Describe dissolution in terms of diffusion layer.
Consider the simple model of dissolution in your answer.
As drug particle dissolves, a diffusion layer is formed with solubilised drug particles at quite a high concentration. This diffusion layer is saturated.
This concentration decreases as you get further away from the drug particles.
A concentration gradient is established when drug molecules are removed into a different compartment when drug molecules are rapidly absorbed from the GI tract.
As these molecules diffuse down the concentration gradient from saturated diffusion layer, more and more drug molecules will dissolve and replace them and so diffusion layer remains saturated.
What are sink conditions?
This is where as soon as drug molecules dissolve, they are being removed and partitioned into the blood.
What is the rate-limiting step in this model?
Rate of dissolution.
What assumptions are made in sink conditions?
First-order kinetics
Concentration of drug is always greater than concentration in blood.
Why is it possible to overestimate the rates of ionisation and dissolution of weak acids/drugs?
The pH of the diffusion layer around each drug particle may be different.
Why is the dissolution rate of weak acids in the stomach low?
Because the drug is unionised and so poorly soluble in the diffusion layer.
How can we increase the pH of the diffusion layer?
By forming an alkaline salt of the weak acid.
How do alkaline salts promote drug ionisation?
Na+ and K+ salts dissolve rapidly than free acids. Regardless of local pH, because they release OH ions which promote drug ionisation.
Name the generalisations made for oral drugs.
Small hydrophilic compounds permeate through paracellular water channels.
Lipophilic compounds permeate by partition into and through the lipid bilayer of biological membranes (transcellular route) in some circumstances
Some compounds permeate via membrane transporters –> this is increasingly being observed and includes drug efflux transporters
Transport through other epithelial and endothelial barriers (e.g. BBB) relies on more advanced understanding and novel drug delivery methods
Large compounds e.g. synthetic peptides and protein-based biologics raise a number of problems
What is LogP?
Log P is a measure of lipophilicity: it is the partition coefficient of an unionised drug between aqueous and lipophilic phases
What is Ka or pKa?
The dissociation constant Ka or pKa describes the extent to which a drug is ionised
pKa is the pH at which [ionised] = [unionised]
What is the distribution coefficient?
Distribution coefficient (D) is the “effective” partition coefficient accounting for the degree of ionisation:
What is D/logD dependent on?
pH
What is the equation used to calculate LogD?
Log D = log P – log {1 + antilog (pKa - pH)}
