Quality Control And Dissolution Testing Flashcards
What are the three aspects of quality control?
*critical material attributes
*critical process parameters
*critical quality attributes
What are solid dosage critical quality attributes?
*tablet thickness- should be controlled within 5% or less of standard acceptance value
What are critical material attributes?
*physical properties of raw materials- bulk density, compression granulation properties, particle size etc
What are the critical process parameters?
*tablet die size
*punch length
*loading force
*compress speed
How is the uniformity of mass of tablets tested?
*weigh 20 randomly selected tabs individually
*determine average mass
*pass- no more than 2 of individual tab masses deviate from average by more than..
-Average mass 80mg or less = 10%
-Average mass 80mg<x<250mg = 7.5%
-average mass 250mg> = 5%
In what two ways can uniformity of dosage units be demonstrated?
*content of uniformity
*mass variation
What is a disintegration test?
Break down of tablets within a prescribed time when placed into a liquid medium under experimental conditions
What are the conditions for a disintegration test?
*apparatus- no more than 18mm long
*six chambers
*1L beaker
*temp 35-39°C
*frequency raising and lowering = 29-32 cycles per min
How is the disintegration test carried out for uncoated tablets?
*pure water
*for 15 mins
*disintegration should be completed within time
How is the disintegration test carried out for gastro resistant tablets?
*0.1M hydrochloric acid solution
*2 hours
*should be no sign of crack or disintegration
*acid replaced by PBS pH 6.8
*60 mins
*examine state of tabs
What is the friability test?
To monitor the break down of tablets under force
How is the friability test carried outL?
*if one tab mass <650mg, use tablet mass total of 6.5gram
*if one tab >650mg, use 10 whole tabs
*rotate drum 100 times
*remove tabs
*pass= mass loss less than 1%
What does an extremely hard tablet suggest?
Excessive bonding between API and excipients= prevent proper dissolution of tab for accurate dosage
What does a softer tablet suggest?
Weak bonding so premature disintegration when ingested
Can also break or chip during manufacture
What is the dissolution profile important for?
*highlight any change to process parameters
*machine used
*manufacturing site
*suppliers of excipients
Helps with post approval
What is a biowaiver?
Similarity between two dissolution profiles allows some in vivo bioavailability and bioequivalence studies to be waived, based on the BCS
What equation is used by FDA in regulatory testing to biowaive similar drugs?
F2
*F2>50 = two similar dissolution profiles
What is dissolution?
Process in which solid dissolves in solvent
Mass transfer from solid to liquid phase
What is the rate of dissolution?
Amount of drug substance that goes into solution per unit time (kinetic process)
What standard conditions need to be considered when looking at rate of dissolution?
*liquid/solid interface
*temperature
*solvent composition
What is a dissolution test expected to be?
*appropriately discriminatory
*rugged/robust
*reproducible (reliable)
What is the diffusion layer model theory?
*dissolution takes place without any forces - simple
*2 stages:
1.solid solution forms STAGNANT film or DIFFUSION layer at solid/liquid interface (basically surrounds drug particle)- saturated with drug- happens rapidly on water contact
2.diffusion of solute from stagnant layer to bulk solution- slower- rate determining- mass transfer
What is the Noyes-Whitney equation?
dC/dt= k(Cs-C)
dC/dt= rate of increase of dissolved drug concentration
k=rate constant of dissolution
Cs= saturation solubility of drug in bulk sol
C= concentration of drug in bulk at time t
What are sink conditions?
*system is always dilute so dissolution process isn’t hindered by build up of solute
In vivo sink condition is maintained always due to rapid absorption after dissolution- drug concn doesn’t build up
What are non sink conditions?
In vitro for poorly water soluble drugs, drug concn builds up so dissolution hindered
What order of kinetics is sink conditions?
Zero order
What is the order of kinetics under non sink conditions?
First order
What are the 3 dissolution apparatus used for solid dosage forms?
*paddle
*basket
*flow-through
What are the 3 dissolution apparatus used for transdermal patches?
*disk-assembly method
*cell method
*rotating cylinder method
Why are paddle apparatus vessels covered?
To prevent evaporation
Why may sinkers need to be added to paddle apparatus?
To retain a solid dosage form at bottom of vessel for testing if it’s buoyant
What is a bio relevant dissolution method?
Using the same conditions as the GI composition ie pH etc
Artificial stomach-duodenum model
