dissolution Flashcards
What is dissolution and what is it’s relevance in pharmaceutics?
A process required before a drug can be absorbed. Tests are relevant to the safety and efficacy of many common dosage forms
Describe processes occuring when going from tablets to granules to particles.
Disintegration occurs to go from tablet to granules.
Deaggregation occurs to go from granule to particle.
Dissolution occurs to go from particles to molecules in solution.
These processes may all occur simutaneously with the release of drug from the delivery form.
What is the rate limiting step in srug absorption?
Dissolution may be the rate limiting step to drug absorption for poorly water soluble drugs (Noyes-whitney equation).
How does dissolution relate to diffusion?
A diffusion layer is present in a solution, where this can be seen through the relationship of flux and the noyes-whitney equation.
Flux is equal to the diffusion coefficient times the difference in dosage concentration and concentration in the bulk solution, divided by the thickness of the diffusion layer.
Give Noyes-whitney equation and describe the aspects.
dM/dt = DS/h x Cs-C dM/dt: dissolution rate D: diffusion coefficient of solute in solution S: SA of solid Cs: solubility of solid C: conc of solute of bulk at a time h: thickness of diffusion layer
What factors affect dissolution rate?
Diffusion coefficient: solvent type, viscosity, temperature and drug properties
Surface area: particle size, shape and disintegration
Solubility of solid: solvent type, pH, temperature, polymorphic form of drug
Concentration of solute in bulk: volumes of medium/sample, fluid turnover rate
thickness of membrane: stirring and agitation
What are sink conditions?
Sink conditions are when the Cs is significantly higher than drug in the medium that it is dissolving into. This gives a constant rate of diffusion across the diffusion layer.
Describe sink conditions with an example
In the body, because drug is constantly being absorbed, sink conditions will apply as the Cs will constantly be greater than the C.
Describe non sink conditions with an example
Closed environments such as water in a glass follow non sink conditions. This is as there is no ‘exit’ for dissolved particles, so bulk liquid concentrations accumulate causing the rate of dissolution to decrease.
How does dissolution behave in terms of kinetics
Under sink conditions, the rate of dissolution follows zero order kinetics.
Under non-sink conditions, dissolution rate follows first order kinetics.
what is the Hixon-crowell cube root law and what does this apply to?
The hixon-crowell cube root law expresses that the dissolution rate of uniformly sized drug particles is based on the cube root of the weight of paticles.
M0^1/3 - M^1/3 = kt
Why is dissolution testing performed, and what is determined?
DIssolution tests are conducted to determine drug release patterns, physiological availability and bioavailability of drugs. This is a tool for quality control, and can be tested on tablets, capsules, or granules.
What is the waiver of in-vivo BA and BE studies?
This is for rapidly dissolving solid oral dosage forms that exhibit high enough solubility, permeability and has a wide therapeutic index.
What is the USP1?
Basket method;
basket containing drug will be put into a dissolution medium at a set temperature, and is rotated. Samples of solution is extracted and tested for concentration to find the dissolution rate.
- This method may be prefered as it is easier to removed the drug from the assembly to test the solution concentration for the drug.
What is the USP2?
Paddle method;
Drug is put into a beaker of dissolution medium at a set temperature, where a paddle is in the centre. This paddle rotates, and a sampling tube is present to extract some solution to test for concentration.
Methods can be modified based on individual requirements.
