Lecture 12 Flashcards
Why is dissolution important?
When you take an oral tablet, dissolution must occur before the drug can be absorbed.
The processes that effect drug absorption rely on dissolution.
Tablets put into dissolution medium need water to stimulate its dissolution.
What is an ineffective drug?
if an oral tablet didnt dissolve until 1 hour
What is dissolution
is a process that drug from a solid state to a solution state.
How does dissolution occur?
water must first diffuse into the tablet matrix before the drug can slowly dissolve and diffuse out.
So still need to know about fick’s law (of diffusion)
What happens if there’s a slow dissolution?
the drug cannot dissolve thus the bioavailability will decrease
Why does the drug start falling apart from the point of taking the tablet to the point of drug effect?
the tablet is made of a lot of small granules which are bound together.
when contact with water they will fall apart easily.
What is the falling apart process called?
disintegration
What happens before the drug can be available for absoprtion?
The drug is in an aqueous environment and in contact with water, so water molecules Can diffuse into the particle matrix and cause the drug to start going into the solution based on the diffusion process.
when can the drug be absorbed?
when it is in solution
What are the 3 process that occur once a solid drug is taken?
disintegration
dissolution
absorption
these can occur at the same time as the release of the drug from its delivery form
What results if any of the steps are affected?
it can affect the rate of drug absorption or the extent of abosrption
When might dissolution be a rate limiting step of drug absorption?
in the case of poorly water soluble drugs, which quite a number of them are.
What are some exceptions of drugs not going through this dissolution process?
controlled release drug,
a solid tablet maintained as a tablet and only allowing release of drug from the surface
so not all tablets have all 3 processes
What is the noyes whitney equation?
Describes the dissolution rate of a solid in relation to the properties of the solid and the dissolution medium
What are the two forms of the NW equation?
dM/dT=DS/(Cs-C) or dC/dT=DS/Vh(Cs-C) where:
M= mass of solute dissolved in time t dM/dT= rate of dissolution (mass/time) D= diffusion coefficient f the solute in the solution S= surface as of the solid Cs= solubility of the solid C= concentration of the solute in the bulk at time t h=thickness of the diffusion layer V= volume of solution
What does the NW theory state?
there is a layer around the tablet where there is a concentration gradient formed.
This layer has a thickness of h
The surface area of the solid is s.
Beyond this layer mixing occurs in solution, so is called the bulk solution.
How is the drug absorbed (according to NW equation)
When the drug is absorbed it is done so like a sink. I.e. At first, the concentration is very low.
The maximum concentration dissolved should be the solubility. This solubility is constant In a specific condition.
If this concentration is constant, there is a steady state diffusion.
The Concentration gradient is also constant. So this is a steady state which you can apply fick’s first law to.
We know the solubility next to the surface is fixed.
in the bulk solution it may seem the concentration gradient is always fixed. But in reality solubility is changeable.
In the static diffusing layer, the thickness is h. But when the tablet is going through, for example the GI tract, the thickness of the fixed layer can be changed.
if the surface area is bigger, more drug will be available to dissolve into the solution
But the tablet gets smaller and smaller, then the surface area also changes.
What should the flux from the solubility dosage form be proportional to?
the concentration gradient (line Cs-C/h)
