Tablet Testing Flashcards
What are properties of an ideal tablet?
- should be acceptable to patient
- contain right drug content
- pleasing appearance
- consistent weight, size and shape
- release drug in reproducible and predictable manner
- good chemical, physical and microbiological stability
- suitable packaging
- strong enough to keep shape during manufacture, processing, packaging, shipping and use
- exempt of contaminants
What tests are performed on tablets?
- appearance; devoid of cracks, chipped edges and that colour is uniform
- thickness and diameter; should not exceed 5% of mean thickness
- diameter can vary by 3% for tablets with diameter above 12.5mm and 5% for tablets with diameters less than 12.5mm
- uniformity of weight
- uniformity of content
- hardness and friability
- disintegration
- dissolution
How is uniformity of dosage form measured?
- uniformity of mass
- uncoated, film-coated tablets if API content is over 25mg or contributes to over 25 wt%
- uniformity of content
- all others
What can excessive variation in mass be a result of?
- formulation
- process development
- equipment maintenance
Paracetamol tablets have been made in the following proportion:
- Paracetamol: 21
- Lactose: 37
- HPMC: 8
- Starch: 5
The weight of granules after drying was 80g. Moisture content of the dried granules was 8%.
5% w/w starch and 0.5% w/w magnesium stearate was added.
Calculate the fill weight (mg) to produce tablets containing 500mg paracetamol.
- work out % API
21/71*100 = 29.6% of dry powder mix is paracetamol
- work out w/w addition calculations
4g starch and 0.4g MgSt
- 4g material
- using moisture content, work out how much of granule mass is powder
- 6g of powder
- work out how much of this is API
- 6 x 21/71 = 21.77g
- do amount of API/total tablet mix as a ratio to work out fill weight
- 77g drug/84.4g tablet mix = 0.5g drug/answer
answer = 1938mg
What is wrong with a tablet that is too hard or soft?
too hard = may not disintegrate
too soft = will not sustain further processing, such as coating or shipping
What does friability measure and what is the requirement?
- attrition method measures tendency to chip or fragment
- mass loss should not exceed 1%
How do disintegrants work?
- enabling water entry (wicking)
- swelling
- releasing gaseous material
- effervescent tablets
Describe wicking in comparison to swelling.
wicking
- water uptake depends on
- wettability (surfactants help)
- pore size distribution
- disintegrant addition
- compression forces
swelling
- impact of porosity
- fluid absorbed, disintegrant size increased
What is intergranular and extragranular disintegrant addition?
intergranular - before granulation
extra - after granulation ; 20-50% wt/wt of disintegrant added
Why would there be a slow rate of drug dissolution?
no disintegrant used or conc too low
What are properties of disintegrants?
- small particle size for high SA
- hygroscopic material as water absorption is important
- gas liberating for effervescent tablets
Give exmaples of convential disintegrants and superdisintegrants
conventional
- starch 5-10%
- poorly compressible
- higher amount needed
- wicking low
- microcrystalline cellulose 5-10%
- wicking activity
superdisintegrants
- sodium starch glycolate 2-8%
- free flowing
- rapid swelling
- croscarmelose 1-5%
- rapid swelling
- wicking
- crospovidone 1-5%
- wicking activity high
What is dissolution testing?
determination of drug release rate
What is preformance of tablets disintegration test affected by?
- disintegration media used
- temp during the test
- formulation factors
What factors must be standardised in a dissolution test?
- factors affecting drug solubility
- composition, pH and temp of dissolution medium
- agitation speed
- factors affecting dissolution
- conc of dissolved substances - sink vs non sink conditions
- fluid flow in dissolution chamber
- factors affecting quantification
- analytical method choice - sensitive enough to detect drug
What factors affect disintegration/dissolution?
- solubility/hygroscopicity of powder formulation
- type and quantity of disintegrant used
- type and quantity of binder used
- addition of lubricant
- manufacture process selected
- how compact were granules
- addition of lubricants and antiadherents
- what compression force was used - if it was too low the pores are too big for water to be trigerring disintegration
Why is dissolution important and how can you improve it?
rate limiting step as drug needs to be in solution to be absorbed
- using a polymorph, salt or amorphous form
- particle size reduction
- matrix formed
- drug dissolved or finely suspended in matrix
- dissolution enhancer
