Tableting III Flashcards
Manufacturing problems and testing non / compendial
Compendial ( Official) QC tests
what are the different types of tests?
1- Uniformity of content of active ingredient (Uniformity of weight & Content uniformity)
2- Friability
3- Disintegration test
4- Dissolution test
Non-compendial (Non-Official) tests
what are the different types of tests
1- Tablet thickness
2- Tablet hardness / crushing strength
What are 4 different manufacturing problems
Capping and Laminating
Sticking, Picking and Filming
Chipping and Cracking
Mottling
State and describe 4 main manufacturing problems in tablet manufacturing (4 marks)
One main manufacturing problem is capping and lamination. capping involved the main part of the tablet coming off as a cap and lamination involves the tablet separarting into two or more layers
Another is sticking and picking and filming. sticking is when the tablet sticks to the face of the press punch. picking is where the granules stick to design in the punch tip.
Another is chipping and cracking, where the tablet can crack or chip
Finally we have mottling. this is an unequal distribution of colour with light or dark spots standing out in an otherwise uniform surface
What should tablets include in quality tests for tablets?
Correct dose / weight / content uniformity
controlled and reproducible dissolution,
sufficient hardness and low friability,
aesthetically pleasing,
safe packaging
Uniformity of weight - sample, acceptable % deviation
we use this test if the tablet is mostly drug
BP: 20 tablets, USP: 10 tablets
(80 mg > X = ± 10%) (250 mg > X > 80 mg = ± 7.5%) (X > 250 mg = ± 5%)
so if its less than 80 its 10 percent
its its more than 80 but less than 250 its 7.5
if its more than 250 then its 5 percent variation
Uniformity of weight - causes of weight variation
- The size and distribution of the granules being compressed (presence of too large or too fine granules then it can cause uneven weight).
- Poor flow (cause incomplete filling of the die).
- Poor mixing (lubricant and glidant not well distributed).
- Lower punches of unequal lengths, the fill of each die varies because the fill is volumetric.
Content uniformity
Sample - what to do
Randomly select 30 tablets from the batch of produced tablets.
10 of these are assayed individually for drug content using a suitable analytical method. (uv spectroscopy and HPLC)
The content of ALL 10 individual tablets should fall within specified limits in terms of % deviation from the mean [85-115%].
Repeat with 20 tablets if fail
Friability
Sample - 10 whole tablets is over 650 mg
Dedust, weigh, tumble in Perspex drum 100 times (4 mins). Reweigh. F = (W0 – W / W0) * 100
1% limit
Disintegration - characterised by
and process
what is the uncoated tablets in water disintegration limit
Fluid penetration
particle separation
BP – 6 glass tubes with 10 mesh screen at bottom, 1L beaker simulated body fluid at 37 degrees C.
Basket moves up and down.
Note time when all particles have passed through mesh.
Uncoated tablets in water disintegration limit is 15 mins.
Dissolution - what does it measure
intermediate release time
rapidly dissolving time
It measures the portion (%) of the active that:
1) has been released from tablets/capsules
AND
(2) has dissolved in the dissolution medium during controlled testing conditions within a defined period
so percent of drug that’s released and dissolved
IR = 75% in 45 mins,
Rapid dissolving = ~85% in ~30 mins (etc)
Hardness/ tensile strength
what is hardness tester measured in
Crushing strength – diametric compression to point of fracture. Tensile strength = (2crushing strength) / (πdiameter*thickness) (2P/πDH)
Hardness tester – measured in kiloPonds (kP)
Why is tablet hardness important to mesure
Hardness can affect tablet disintegration time.
If the tablet is too hard it may not disintegrate within the required period of time. If tablet hardness is high, but tablet disintegrate within the required time, we accept the batch.
If tablet too soft it may not withstand the handling during subsequent processing such as coating, packaging.
Factors affecting tablet hardness
Compression force & speed (if plastic)
Binder & its concentration
Lubricant: Magnesium stearate
Method of granulation:
Wet granulation produces harder tablets than DC.
Dry granulation can give good hardness.
Tablet Thickness
The thickness of the tablet is the only dimensional variable related to the tablet compression process.
Generally, it is measured with a micrometer.
The thickness should be within ± 5% variation of a standard value and must control for patient acceptance and make the tablet packaging easier
