Lecture 8: Tablets 2 Flashcards
What are the important properties of a tablet to assess its performance?
- Tablet breaking/ crushing force
- Friability
- Disintegration
- Dissolution
What is tablet breaking/crushing force?
The force neceassry to cause a tablet to fracture when compressed between 2 rigid platens
What are factors that affect the tablet breaking force?
- Formulation components
- Process used to make the formulation
- Compression process used
- Geometry and thickness
etc
What is an acceptable tablet breaking force?
Should be high enough that it has a good appearance and can withstand further processing and handling
But not too high that it cant disintegrate or dissolve properly
What are the requirements for the platens when measuring tablet breaking force?
- Should be parallel to each other
- Polished and smooth surface
- Perpendicular to the direction of movement
What is the process by which the tablet breaking force is measured?
- Tablet is weighed
- The thickness is measured
- The tablet it put into the chamber which applies the force and measures the force need to crack it
What parameters of the equipment are kept constant during the measurement of tablet breaking force?
Rate of platen movement or the loading rate
Why is it importnat to maintain a constant loading rate during tablet breaking force testing?
- Keeping a steady speed when applying pressure helps to measure the strength of the tablet better
- Under different loading rates, materials can have different breaking mechanisms. When the material changes from ductile to brittle faliure, the breaking force required increases. So to keep this contsant, we dont change the loading rate
- A steady breaking force helps prevent unexpected kinds of breaking (like crushing or sliding apart), which minimises variability.
Whats a drawback of using a constant loading rate to measure tablet breaking force?
It might be slow, so it can be inefficient when you have to measure many samples during manufacturing.
Explain how tablet geometry can affect tablet breaking force.
- A thicker tablet requires greater breaking force (assuming same diameter)
- Scored tablets: the break easier when the score is perpendicular to the platens –> a more general breaking force is obtained when you put the score parallel to the platens
- Tablets with an elongated shape will have a different breaking force when you put it in different orientations
hence you must standardise the geometry and the orientation of all the tablets
What is the minimum sample size needed to test tablet breaking force?
6 tablets
How do you calculate the tensile strength of a cylindrical tablet after measuring its breaking force?
tensile strength =(2 x breaking force) / (pi x tablet diameter x tablet thickness)
What is the minimum acceptable tensile strength of a tablet?
2MPa
What is friability of a tablet?
The ability of the tablets to withstand stress against absrasion.
How do you test the friability of tablets?
- De dust tablets and measure their weight
- Put them in a rotating drum with a pre determined speed and number of revolutions (usually 100)
- Drum will rotate and toss the tablets around
- Remove loose dust and measure the weight of the tablets again
5.Calculate percentage weight lost
What is the minimum sample size needed to test tablet friability?
- If weight of one tablet <= 650 mg : take enough tablets such that the total mass is as close as possible to 6.5g
- If weight of one tablet > 650 mg : take 10 tablets (weight is atleast 6.5g)
What is a good tablet friability?
- The weight change of the tablets should be less than 1%
- The tablets should not be cracked, cleaved or broken after tumbling (otherwise failed)
When is a tablet considered to be completely disintegrated?
Complete disintegration is the state in which any residue of the unit, except fragments of insoluble coating or capsule shell, remaining on the screen of the test apparatus or adhering to the lower surface of the disk, if used, is a soft mass having no palpably firm core.
What are the apparaus and conditions used to measure tablet disintegration?
- Basket rack assembly –> basket moves up and down into the immersion fluid, 55m distance moved
- 1000mL in beaker
- Height 138-160 mm,
- Inside diameter 97-115mm
- Temp 35-39 deg C
- At the highest point of the upward stroke, the wire mesh remains at least 15 mm below the liquid surface
- For the downward stroke, the wire mesh is not less than 25 mm from the bottom of the vessel
- Time required for the upward stroke is equal to the time required for the downward stroke
- The change in stroke direction is a smooth transition (vs an abrupt reversal of motion)
- The basket-rack assembly moves vertically
What are the dimensions of the wire cloth in the basket rack of the disintegration test apparatus?
Plain square weave with 1.8 – 2.2 mm apertures
Wire diameter: 0.57 – 0.66 mm
What is the disk used for in the disintegration test apparatus?
- Ensure submersion of the dosage unit and the necessary surface wetting to facilitate disintegration
- Used for uncoated or plain coated tablets only
Explain the process of doing the disintegration test.
- Pour water/ other medium like simulated gastric fluid into the beaker (1000mL)
- Maintain temperature at 37 deg (+/- 2deg)
- Place 1 tablet in ech basket and add a disk
- Start vertical movement of the basket rack
- The apparatus will measure the time taken for the tablets to disintegrate (for the manual apparatus, you have to observe and time yourself).
What would you do if some tablets fail to disintegrate in the disintegration test?
- If more than 2–> test failed
- If 1-2 tablets failed, repeat the rest on 12 additional tablets
- Requirement is met if not fewer than 16 of the total 18 tablets are disintegrated
What is the ideal disintegration time for a tablet?
Ideally less than 10 mins
At most 15 mins
What are the 3 mechanisms by which a tablet disintegrates?
- Swelling
- Strain recovery
- Wicking
Explain how a tablet disintegrates by the swelling mechanism.
- Disintegrant gets hydrated and expands 3 dimensionally
- This causes the bonds holding the tablet together to break
- Fragments of the tabelt are detached form the polymer
Why are disintegrants often crosslinked polymers?
- Crosslinkingreduces the solubility of the polymer, which minimises gelling
- Gelling can increase the viscosity within the tablet, which slows down swelling and disintegration
- If the polymer is too viscous, it can form a plug that acts as a binder, which opposes the breaking of bonds inside the tablet for disintegration
Give some examples of disintegrants that are crosslinked polymers, and cause disintegration by the swelling mechanism.
- Sodium starch glycolate
- Croscarmellose sodium
Explain how a tablet disintegrates by the strain recovery mechanism.
- Disintegrant gets hydrated and expands 1 dimensionally
- This causes the bonds holding the tablet together to break
- Fragments of the tabelt are detached form the polymer
- These disintegrants have a spring like mechanism, where the energy stored during compaction is released after hydration.
Give some examples of disintegrants that cause disintegration by the strain recovery mechanism.
Crospovidone
For disintegration by the strain recovery mechanism, how can we make the disintegrants more effective?
- By applying a greater pressure during compaction
- Since those disinetgrants have a spring like mechanism, when more pressure is applied, more energy is stored in the disintegrants which is released during hydration.
Explain how a tablet disintegrates by the wicking mechanism.
- Liquid penetrates the pores of the tablet by capillary action
- This causes dissolution/shape recovery/ swelling, causing the tablet to disintegrate
Explain fast and slow wicking.
Fast wicking: water enters the tablet rapidly, and the tablet burts open and disintegrates at once
Slow wicking: Water enters the tablet slowing and it gradually disintegrates from the surface to the core
How does pH affect disintegration?
- It affects ionisation
- Ionised polymer swells more than an unionised one, because the charges in the ionised polymer repel each other, and interact better with water
- A non ionisable polymer is unaffected by water
How does the ionic strength affect disintegration?
When there’s a high ionic strength, charged polymers (ionizable polymers) don’t expand or “uncoil” as much. This happens because the extra ions in the solution “shield” the polymer’s surface charges. This reduces the pressure difference between the polymer and the solution, which lowers its swelling ability.
Swelling of non-ionizable polymer is not affected by ionic strength
How does temperature affect disintegration?
Disintegration is generally faster at higher temperature
How does viscosity affect disintegration?
Disintegration was generally slower at higher viscosity of the medium
Food can induce changes in viscosity of the medium
What are the types of dissolution apparatuses?
Apparatus 1 (Basket Apparatus)
Apparatus 2 (Paddle Apparatus)
Apparatus 3 (Reciprocating Cylinder)
Apparatus 4 (Flow-Through Cell)
What is Apparatus 1 (Basket Apparatus) useful for?
Tablets that will float if not kept in the basket
like effervescent tablets
Explain how dissolution apparatus 1 (basket apparatus) works.
- Basket where the tablet is kept - immersed into the medium
- Basket rotates while the tablet dissolves and diffuses into the medium - where conc is measured
What are the 4 main components of apparatus 1 (basket apparatus)?
motor, metallic drive shaft, cylindrical basket and vessel
In dissolution apparatus 1 (basket apparatus), what is the cylindrical basket and metallic drive shaft made out of?
Made of stainless steel (316) or other inert material
What is the coating that is sometimes used on the cylindrical basket in dissolution apparatus 1 (basket apparatus)?
A gold coating of about 2.5 µm may be used
In dissolution apparatus 1 (basket apparatus), what is the distance specification of the cylindrical basket from the bottom of the vessel?
25 +/- 2mm
In dissolution apparatus 1 (basket apparatus), what is the vessel made out of, how much medium is added inside, and what temperature should be maintained inside the medium ?
The vessel is the part that holds the medium
It is made of glass or other inert transparent material
Volume 1L/2L/4L
Temp should be 37 +/- 0.5
Explain how dissolution apparatus 2 (paddle apparatus) works.
- Tablet is placed directly inside vessel with medium in it
- There is a paddle that rotates (to simulate churning in the GIT?)
What kind of tablet can be used to test dissolution using dissolution apparatus 2 (paddle apparatus) ?
Tablets that sink to the bottom
What are the components of dissolution apparatus 2 (paddle apparatus) ?
- Motor
- Metallic drive shaft with a blade (paddle)
- Vessel
What is the distance maintaned between the paddle and the bottom of the vessel in dissolution apparatus 2 (paddle apparatus) ?
25 +/- 2mm
In dissolution apparatus 2 (paddle apparatus), why is it important to standardise the dimensions of the paddle?
Paddle dimensions are extremely critical as any change in the surface area of the paddle will change the stirring characteristics and hydrodynamics of the system
Explain how dissolution apparatus 3 (reciprocating cylinder) works.
- Tablet is put into reciprocating glass cylinder that is immersed inside the vessel with the medium
- The cylinder moves up and down
What are the components of apparatus 3 (reciprocating cylinder) ?
- Motor
- Metallic reciprocating shaft (the thing holding the cylinder)
- Reciprocating cylinder
- Vessel (cylindrical and flat bottomed)
Explain how dissolution apparatus 4 (flow through cell) works.
- Tablet is put into flow through cell on top of glass beads
- Medium source is external - a pump delivers the medium into the flow through cell at a constant rate
- That medium flows out of the cell and is collected to be analysed
What is dissolution apparatus 4 (flow through cell) useful for?
For testing low solubility drugs, drugs prone to rapid degradation and those systems requiring swift pH changes in the media
What are the components of apparatus 4 (flow through cell) ?
- Reservoir of dissolution medium
- Water bath
- Pump
- Flow-through cell
What is the temperature maintained in apparatus 4 (flow through cell)?
37 +/- 0.5 deg C
In apparatus 4 (flow through cell), what is the flow through cell made out of?
Inert transparent material
How would you use dissolution apparatus 2 (paddle apparatus) to test an immediate and extended release tablet?
- Place the dissolution medium into the vessel
- Equilibrate the dissolution medium to 37 ± 0.5 ºC
- Place 1 tablet in the apparatus
- Immediately operate the apparatus, while keeping the vessel covered
- Withdraw samples from a position that is between the surface of the dissolution medium and the top of the rotating basket or blade, not less than 1 cm from the vessel wall
- Analyze the samples
How would you use dissolution apparatus 2 (paddle apparatus) to test a delayed release tablet?
Two stage —> acid stage & buffer stage
1. Acid stage: Place 0.1 N HCl (1000 mL) in the vessel, equilibrate to 37 ± 0.5 ºC, place tablet, operate for 2 hours, withdraw samples during the operation to analyse
2. Buffer stage: drain acid, place pH 6.8 phosphate buffer (1000 mL) in the vessel, Adjust pH with 2 N HCl or 2N NaOH until pH = 6.8 ± 0.05, operate for 45 mins, withdraw samples during the operation to analyse
What are some manufacturing steps involved in tablet manufacturing?
Milling
Blending
Granulation
Powder compaction
Coating
What is milling?
using machine to reduce particle size
Is milling a top down or bottom up approach?
top down
What are the 2 types of mixers used int he blending/mixing stage of tablet manufacturing? Explain what they do and give examples.
- Diffusion mixers: increase the powder bed, allowing the particles to move more freely, allowing them to mix
- eg: V blender and double cone blenders: use gravity & gentle rotation for mixing - Convection mixers: These mixers rely on mechanical paddles or blades to physically move particles.
= eg: ribbon blenders
What are the 4 general stages of compaction?
Stage 1: Volume reduction and particle rearrangement.
Stage 2: Particle deformation—elastic (reversible) and plastic (irreversible).
Stage 3: Particle fragmentation for further volume reduction.
Stage 4: Formation of interparticulate bonds for a solid structure.
How do you calculate compaction pressure of a tablet?
compaction pressure = compaction force / applied area
How do you calculate solid fraction of a tablet?
solid fraction = tablet density / material true density
How do you calculate tablet tensile strength of a tablet?
tensile strength = 2(breaking strength) / (pi x diameter x thickness)
How does tableting speed affecting compaction?
- Materials used for compaction are ductile, so their deformation is affected by the speed
- A higher tableting speed can cause a decrease in tablet strength for materials that deform by plastic deformation or materials that have a high degree of elastic recovery
- When materials with high elasticity are pressed quickly, issues like capping (when the tablet’s top layer separates) and lamination (tablet layers split apart) can occur.
What are the 3 kinds of compaction equipment?
- Single station pression
- Rotatory tablet press
- Universal testing machines (e.g. Carver press, Instron-type machine, and compaction
simulator)
How does a single station press work?
- The powder is filled into the die
- Lower punch is stationary, upper punch moves with a stamping motion to compress into tablet
- Low operating speed
How does a rotatory tablet press work?
- Has more than one set of punches
- Compaction is a continuous process occurring on a rotating turret that moves the upper and lower punches between two pressure rollers, producing a squeezing action
- Requires relatively large quantities of material
- High operating speed
Revise compaction simulators later pls
no flashcards
What is the purpose of tablet coating?
- masking unpleasant API taste
- Good appearance
- Protection for fragile tablets
- Modified release of API
What are the 3 kinds of coating equipment?
- Pan
- Perforated pan
- Fluid bed processor
How does the pan work to coat tablets?
- Tablet loaded onto the pan which is a spherical thing
- coating sprayed
- Drying air blown onto the surface of the tumbling bed + exhaust air withdrawn by a manifold situated at the outer perimeter of the pan opening
- This works well for coating with highly volatile organic solvents (e.g. ethanol), but not water
How does the perforated pan work to coat tablets?
look at lecture notes
How does the fluid bed processor work to coat tablets?
look at lecture notes
What are some tablet defects?
- Lamination
- Capping
- Sticking
- Picking
What is capping?
A tablet defect
A fracture occurs at the top of the tablet and the top, or cap, separates itself from the body
of the tablet
Why does capping and lamination occur?
Caused by air trapped in the powder material during the compression stage.
When a tablet is compressed, air is expelled from the powder granules allowing each of the particles to stick together.
The press is designed to allow the air to dissipate during the compression process
As the air is released from the granules, it can also push very fine dry granules fines outwards —> fines generally do not stick together and prevent the granules at the tablet top from being compressed
Faster press speed —> capping more likely to occur
What is lamination?
Tablet splitting into two or more separate horizontal layers
* Cause is similar to capping
How would you prevent capping and lamination from occuring?
- Adjusting the upper punch penetration depth in the die
- Perform pre-compression (an initial compression step before the main compaction step, at
a lower pressure) - Increase the dwell time of tablet in the die
What is sticking?
Powder stick to the face of the press punch
* Results from cohesive forces inside the tablet being weaker than the adhesive forces
between the tablet and the punch surface
What is picking?
Similar to sticking; powder stick to the design embedded in the punch tip such as in
lettering or logos
* Occurs when embossing especially letters with small enclosed areas such as those found in
the letters “B,” “A,” and “0” are difficult to manufacture cleanly
How would you prevent sticking/picking of tablets ?
Increase the compression force
* Perform pre-compression to improve powder cohesion
* Reduce punch surface roughness
* Ensure proper mixing of lubricant in the powder
