Quality Control And Dissolution Testing

Question 1

What are the three aspects of quality control?

Answer 1

*critical material attributes
*critical process parameters
*critical quality attributes

Question 2

What are solid dosage critical quality attributes?

Answer 2

*tablet thickness- should be controlled within 5% or less of standard acceptance value

Question 3

What are critical material attributes?

Answer 3

*physical properties of raw materials- bulk density, compression granulation properties, particle size etc

Question 4

What are the critical process parameters?

Answer 4

*tablet die size
*punch length
*loading force
*compress speed

Question 5

How is the uniformity of mass of tablets tested?

Answer 5

*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%

Question 6

In what two ways can uniformity of dosage units be demonstrated?

Answer 6

*content of uniformity
*mass variation

Question 7

What is a disintegration test?

Answer 7

Break down of tablets within a prescribed time when placed into a liquid medium under experimental conditions

Question 8

What are the conditions for a disintegration test?

Answer 8

*apparatus- no more than 18mm long
*six chambers
*1L beaker
*temp 35-39°C
*frequency raising and lowering = 29-32 cycles per min

Question 9

How is the disintegration test carried out for uncoated tablets?

Answer 9

*pure water
*for 15 mins
*disintegration should be completed within time

Question 10

How is the disintegration test carried out for gastro resistant tablets?

Answer 10

*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

Question 11

What is the friability test?

Answer 11

To monitor the break down of tablets under force

Question 12

How is the friability test carried outL?

Answer 12

*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%

Question 13

What does an extremely hard tablet suggest?

Answer 13

Excessive bonding between API and excipients= prevent proper dissolution of tab for accurate dosage

Question 14

What does a softer tablet suggest?

Answer 14

Weak bonding so premature disintegration when ingested
Can also break or chip during manufacture

Question 15

What is the dissolution profile important for?

Answer 15

*highlight any change to process parameters
*machine used
*manufacturing site
*suppliers of excipients
Helps with post approval

Question 16

What is a biowaiver?

Answer 16

Similarity between two dissolution profiles allows some in vivo bioavailability and bioequivalence studies to be waived, based on the BCS

Question 17

What equation is used by FDA in regulatory testing to biowaive similar drugs?

Answer 17

F2
*F2>50 = two similar dissolution profiles

Question 18

What is dissolution?

Answer 18

Process in which solid dissolves in solvent
Mass transfer from solid to liquid phase

Question 19

What is the rate of dissolution?

Answer 19

Amount of drug substance that goes into solution per unit time (kinetic process)

Question 20

What standard conditions need to be considered when looking at rate of dissolution?

Answer 20

*liquid/solid interface
*temperature
*solvent composition

Question 21

What is a dissolution test expected to be?

Answer 21

*appropriately discriminatory
*rugged/robust
*reproducible (reliable)

Question 22

What is the diffusion layer model theory?

Answer 22

*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

Question 23

What is the Noyes-Whitney equation?

Answer 23

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

Question 24

What are sink conditions?

Answer 24

*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

Question 25

What are non sink conditions?

Answer 25

In vitro for poorly water soluble drugs, drug concn builds up so dissolution hindered

Question 26

What order of kinetics is sink conditions?

Answer 26

Zero order

Question 27

What is the order of kinetics under non sink conditions?

Answer 27

First order

Question 28

What are the 3 dissolution apparatus used for solid dosage forms?

Answer 28

*paddle
*basket
*flow-through

Question 29

What are the 3 dissolution apparatus used for transdermal patches?

Answer 29

*disk-assembly method
*cell method
*rotating cylinder method

Question 30

Why are paddle apparatus vessels covered?

Answer 30

To prevent evaporation

Question 31

Why may sinkers need to be added to paddle apparatus?

Answer 31

To retain a solid dosage form at bottom of vessel for testing if it’s buoyant

Question 32

What is a bio relevant dissolution method?

Answer 32

Using the same conditions as the GI composition ie pH etc
Artificial stomach-duodenum model