Flashcards in Lecture 12 Deck (46)
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?
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?
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)
What happens to the dissolution rate if the surface area is bigger?
the dissolution rate should also be bigger
Which variable of the NW equation is not concentration gradient related?
What happens to the surface area if the tablet falls apart into small particles?
the surface area will have increased
How can the static diffusion layer be changed?
it can be reduced by stirring
Why is the volume of the solution important when advising patients taking oral tablets?
if a patient does not drink water the drug may not dissolve as quickly
What factors affect the dissolution rate?
solubility of drug,
thinner diffusion layer
What is the relationship between dissolution rate and the diffusion coefficient?
dissolution rate is proportional to diffusion coefficient
What effects the diffusion coefficient?
solvent and viscosity.
the diffusion coefficient is inversely proportional to the viscosity
What is the effect of high temperatures on the diffusion coeffcient?
higher temperatures give a higher diffusion coefficient
For tablets, If you want to evaluate the tablet performance use skin temperature for something you want to use on the skin.
What is surface area proportional to?
What do sink conditions ensure?
the drug dissolved in the solution should be much smaller than the solubility,
it is quickly removed so that there is always a concentration gradient
each system should have a fixed diffusion coefficient and surface area
How can you find the dissolution rate?
by knowing the volume you add to the dissolution test, the solubiliy of the drug and its static state and thickness are known and fixed
Why is dissolution rate a first order reaction?
only the concentration determines the dissolution rate.
In sink conditions, the dissolution rate can be rated as k where k is a constant number
In what case can fick's first law not be applied in dissolution?
for the case of drug powders
What law can be used to describe the dissolution of drug powders?
hixson-crowell cube root law
What kind of particles can be described usin the HC cube root law?
all particles that are spherical, as well as their sizes
For particles which are the same size in a system, what can you measure if you know the initial mass?
the released amount vs. time
Why is a dissolution test done?
because we cant use people to test the solubility of a drug.
What kind of tests need to be done for poorly water soluble drugs?
human studies as well as dissolution testing
What is biequivalence?
when the result of two different groups are almost the same
e.g. for human studies and dissolution testing for poorly water soluble drugs
What are the 2 different ways of dissolution testing?
1) basket assembly (USP dissolution apparatus 1)
2) paddle method (USP dissolution apparatus 2)
What is the difference between the basket and paddle method?
basket: drug is placed in a rotator in solution
paddle: drug is in solution with a paddle stirring the liquid
How can quick dissolution be achieved?
by faster rotating, however this rotation must be fixed as this will affect the static diffusing layer
Why does the position of the paddle also affect dissolution?
if it is closer to the drug, it gives a bigger stirring effect, so for the USP or BP we always set the position of the edge of the paddle to be 20mm from the bottom of the flask
What are other ways we can change the dissolution rate?
changing diffusion coefficient, solubility and temperature.
solubility is more important
what other factors affect dissolution rate?
the volume of the medium, and the pH of the medium
What does a dissolution profile show?
how much drug is in the tablet. This is done by recording the % of drug that enters the solution over time.