Formulation of Advanced or Complex Medicines 19 SODF5 Flashcards
What is a spinning riffler?
A mass flow hopper with a vibrating chute and rotating carousel
What happens to samples once they have been taken for analysis?
Samples are taken from the bulk material
- moving stream
- sampling thief
These are fed into a spinning riffler, or a cone for quartering
An analytical sample is kept dry for particle analysis, and another sample is dispersed in liquid for assay and replicate analysis
Why is it hard to assign particle size to pharmaceutical particles?
Rarely regular shapes
To describe them, need to use the minimum number of dimensions to provide useful information for the application involved
- length
- width
- depth
Impractical
How can similar sized particles be obtained for testing?
Sieve equipment
- simple test using a nest of sieves
- sieves are woven from wire holes
- tend to be square
- sieves are plates with perforations
- tend to be round
How does sieve analysis work?
Nest of 6 - 8 sieves
- an aperture progression based on v2 or 2v2 change in diameter
Place sample of most coarse sieve and vibrate for specific time
How does air jet sieving work?
One sieve at a time
- start with the finest and remove the fraction under sized
What is the producer’s risk of inspection by sampling?
Chance of rejecting an acceptable batch
What is the consumer’s risk of inspection by sampling?
Change of approving a rejectable batch
What is the threshold for rejecting a batch if there is a minor fault?
500,000 capsules or tablets
sample size 1,250
Accept 7
Reject 8
If 8 faults, reject the whole batch
What factors must solid oral dosage forms be able to withstand during product handling performance?
Measure of integrity of dosage form
- ability to survive handling
Capsules
- hard gelatine capsules
- shell fragility
- soft gelatine capsules
- strength of seal
Tablets
- breaking force
- friability
How is the breaking force of a tablet tested?
Tablet should break into approximately two equal parts
- perfect failure
Result in units of force, N or kg
- precision +/- 1N
Measure 10 tablets and calculate the mean, maximum and minimum
How is tablet friability tested?
% weight loss after standard handling
- 25 rpm for 4 minutes
- can tilt at 10 degrees if necessary
Sample size 6.5g (or 10 tablets if large)
Why is tablet friability important?
Patient/pharmacist - loss of active
Manufacturer - contamination
What are the two ways of measuring dose uniformity?
Simple
- mass variation (MV)
- weigh tablets/contents of hard or soft capsules
- relies on dosage forms being homogeneous in content of API
Complex
- content uniformity (CU)
- assay the quantity in each tablet or capsule
- involves more laboratory time
What are the reasons for poor uniformity of weight or content?
Poor powder flow into tablet dies or capsule powder hoppers
Worn tabletting tools or mismatch of punch lengths
Powder adhering to dosators or dosing disks and tamping fingers
Segregation/insufficient powder mising
Poor choice of lubricant or glidant
Medial particle size too small or too large
Particle size distribution too wide
Tablet friability
Weak capsule powder plugs
