PDD 09: Solid Oral Dosage Forms – Tableting Flashcards
How are tablets formed?
by applying a force to a powder between two die punches
- during this process, compression and consolidation occur
What is compression?
reduction powder volume by gas displacement from the powder blend
- reversible, non-destructive
What is consolidation?
increasing the mechanical strength of the tablet due to interaction between particles during compression
- destructive
What is the predominant factor for tablet strength?
increased particle-particle interaction due to van der Waals forces
What are the two types of tablet presses for tablet production?
- single-punch press (eccentric press)
- rotary press (multistation press)
What is a single-punch press (eccentric press)?
- one die and one pair of punches
- output is up to 200 tablets per minute
- force is applied from upper punch only
- primary use is in the production of small batches of tablets in R&D stage (formulation development or clinical trials)
Single-Punch Press (Eccentric Press)
What are the stages of tableting? (3)
- die filling
- powder flows into the die from the feeder by gravity
- the bottom of the die is closed off by the lower punch
- tablet formation
- the upper punch enters the die and compresses the powder blend until the tablet is formed
- after maximum force application, the upper punch leaves the die
- tablet ejection
- tablet is ejected from the die
- the lower punch rises to push the tablet out of the die
Why is flowability of powders in solid drug formulations so important?
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What is a rotary press (multistation press)?
- primary use is for scale-up and for large-scale production
- possesses a number of dies and sets of punches
- output of over 10,000 tablets per minute
- force is applied from upper AND lower punch
Rotary Press (Multistation Press)
What are the stages of tablet formation? (4)
- compression
- upper punch enters die and gas is displaced
- consolidation
- particle/particle interactions occur
- decompression
- tablet ‘relaxes’ as upper punch leaves die
- tablet expands axially during this process
- if bonding between particles is not
strong enough, the tablet will laminate
- ejection
- tablet undergoes radial expansion
- if lamination occurs, it will occur around the upper edge of the tablet – this is called capping
Tablet Defects
When can lamination and capping occur?
if particles are not compressed enough or if air is entrapped in powder bed during compression
- force transmission is not uniform throughout powder bed
- reduce compression speed
Tablet Defects
What can lead to lamination?
low density zones
Tablet Defects
What can lead to capping?
high density zones
Tablet Defects
What are flowability defects?
- weight and dose variation
- powder sticking
Tablet Defects
What are compactability defects?
- low mechanical strength
- lamination and capping
Tablet Defects
What are friction and adhesion properties defects?
- excessive wear
- tablet picking – sticking of tablets to each other or tools
When can tablet defects occur?
from various stages during the manufacturing process
- the whole process has to be optimized from start to finish
Tablet Defects
What is insufficient mixing?
mottling: uneven distribution of colorants on surface coating
Tablet Defects
What are chemical incompatibility and non-optimized formulations?
- cracking: splitting of tablet coating due to excessive expansion or poor mechanical stress resistance of coating
- peeling: insufficient adhesion between tablet core and coating
What are the quality attributes of tablets?
- tablet should contain correct dose of drug
- appearance should be elegant and consistent
- drug should release from the tablet in a controlled and reproducible way
- tablet should be biocompatible
- tablet should be of sufficient mechanical strength to withstand fracture and erosion during handling
- tablet should be chemically, physically, and microbiologically stable during the lifetime of the product
What are the tests performed to ensure tablet matches specifications?
- uniformity of content (amount of active ingredient(s))
- uniformity of mass
- disintegration testing
- dissolution testing
- mechanical strength testing – attrition testing (friability testing), fracture resistance testing
Tablet Testing
What is the uniformity of content (amount of active ingredient(s)) test?
- collect 10 tablets and measure active ingredient(s) by an appropriate analytical method
- should be within ±15% of the average amount of active drug
Tablet Testing
What is the uniformity of mass testing?
weigh 20 tablets and calculate average mass
deviation of individual masses should not exceed the following limits:
- less than 80 mg: ± 10%
- 80-250 mg: ± 7.5%
- greater than 250 mg: ± 5%
Tablet Testing
What is disintegration testing?
test is carried out by agitating tablets in an aqueous medium at a defined temperature and the time to reach the endpoint of the test is recorded
- basket rack assembly with 6 open ended tubes
- mesh screen at bottom of tube
- basket raised and lowered between 29-32 cycles per minute in immersion fluid at 37°C until tablet is disintegrated
Tablet Testing
What must disintegration time be?
within specified range in Pharmacopoeia (usually 30 minutes)
Tablet Testing
What is dissolution testing?
important way to study the release of a drug from a solid dosage form in vitro
- during a dissolution test, cumulative amount of drug that passes into solution is measured as function of time
Tablet Testing
Why are dissolution tests carried out to do?
- evaluate the potential effect of the formulation and process variables on the bioavailability of the drug
- ensure that preparations comply with product specifications
- indicate the performance of the preparations under in vivo conditions (must be experimentally verified)
Tablet Testing
Describe the dissolution test.
tablet is placed in a chamber containing dissolution medium – depends on application
- ensures sink conditions
- concentration gradient between diffusion layer and bulk solvent is assumed to be constant (solubility lecture)
- stirred vessel methods or continuous flow methods are common
Tablet Testing
What is mechanical strength testing?
set of tests to determine the hardness and friability of the tablet
- different sets of equipment are in use
Tablet Testing
What does the mechanical strength of a tablet affect?
- disintegration and dissolution rates
- physical stability – breaking/chipping upon shipping and handling
- ability to break tablets if needed (splitting)
Tablet Testing
What are the two most common methods of mechanical strength testing?
- attrition resistance tests (friability testing)
- fracture resistance tests
Tablet Testing
What is attrition testing (friability testing)?
test meant to mimic the kind of forces to which a tablet is subjected during handling between its production and its administration
Tablet Testing
What are the methods of attrition testing (friability testing)?
- most common method of attrition testing involves rotation of tablets in a cylinder followed by the determination of weight loss after a given number of rotations
- another method is to shake tablets intensively in a jar
Tablet Testing
What is required during an attrition test (friability test)?
weight loss of less than 1%, along with an absence of physical abnormalities such as capping, cracks, or fractures
Tablet Testing
What is fracture resistance testing?
application of a load on the tablet and determination of the force needed to fracture or break the tablet along its diameter
- particularly important for blister packaged medications to ensure the tablets remain intact during their removal from the packaging
