Section 5 - Tablets Flashcards
What is a tablet?
A unit dose form of medication containing one or more drugs that are compressed as granules or powder to a definite shape
Can tablets have excipients added?
Yes
What is the popularity of tablets due to?
1) Dosing accuracy
2) Stability
3) Patient acceptance
4) Diversity
Drugs in solid state are generally ____ chemically stable
More
Do drugs in the solid state have a longer or shorter half-life?
Longer
Are all tablets swallowed?
No, some are sublingual, implant, or chewable
What are some disadvantages to tablets?
- Solid dose form may cause local irritation to GI mucosa
- May have bioavailability problems since dissolution must occur before drug is available for absorption
What are some attributes that a tablet must have?
- Able to withstand rigors of mechanical treatment during production, packaging, shipping, and dispensing
- Free of defects (cracks, chips, discolouration)
- Reasonable chemical and physical stability
- Contain the proper amount of medication and release it in a predictable and reproducible manner
What are the 2 essential characteristics that materials intended for compression into a tablet must have?
Fluidity and compressibility
Why is fluidity necessary for granulation?
Necessary for the transport of the material through a hopper into a feeder frame or die cavity
What is compressibility?
The property of forming a stable compact when pressure is applied
Do powders generally flow freely?
No
What can poor flow lead to?
Variable fill of the cavity and consequent variation in tablet weight, content, and hardness
Are granules free-flowing?
Yes
Do granules have good compression properties?
Yes
Almost all problems relating to tablet production are caused by ____
A problem w/ the granules
What is the most important step in tablet production?
Granulation
What are attributes that good granulation should have?
- Approach spherical shape
- Present a narrow range of particle sizes
- Have homogenous distribution of all materials
- Have acceptable compression properties
Why should granules approach spherical shape?
To minimize inter-particle friction and static charge
Why should granules present a narrow range of particle sizes?
It provides uniform fill and bridges between particles when compressed
What are acceptable compression properties?
Hard enough to remain intact, yet be able to disintegrate when taken
Are excipients used in granulation? Why?
- Yes
- To confer appropriate properties to granules
What are the benefits of excipients to granulation?
- Some aid in granule formation and flow
- Some aid in compression
- Some aid in disintegration and dissolution
What must an excipient do or not do when added to a granule?
- Not compromise product stability
- Must conform to pharmacopeial standards
Why are diluents used with potent drugs?
B/c drug may have a dose in the microgram range and a diluent is needed to give the product adequate bulk
What are some examples of diluents (fillers)?
- Lactose
- Sucrose
- Mannitol
- Sorbitol
- Calcium sulfate
- Calcium phosphates
- Starch
- Microcrystalline cellulose
What is the choice of filler based on?
- Desired specifications of finished product
- Stability/compatibility aspects of API
What are some properties of lactose crystals that are beneficial to compressibility?
- Crystals tend to be plastic
- Tend to deform under pressure
Is lactose hydroscopic?
No
What is a disadvantage to lactose as a diluent?
Prone to “browning” w/ some drugs, and may lose some compressibility characteristics w/ some drugs
What is sucrose often used for as a diluent?
To impart hardness to tablets, but used in small amounts b/c somewhat hydroscopic
What tends to happen w/ tablets that contain sucrose?
Harden w/ time
Is sucrose prone to browning?
Yes
Is mannitol inert?
Yes
Is mannitol hydroscopic?
No
When is mannitol used as a diluent?
In chewable tablets b/c it feels good in the mouth (cool, smooth, slightly sweet)
Calcium sulfate has ___ solubility
Low
Is calcium sulfate hydroscopic?
No
Calcium sulfate has ____ absorption of oils
Good
Does calcium sulfate harden with time?
Yes
What is microcrystalline cellulose?
Insoluble, inert free-flowing filler which can also function as binder and disintegrant
When is microcrystalline cellulose mostly used?
In direct compression
Microcrystalline must be added ___ to granules to improve binding
Dry
What do binders do?
Hold powders together, causing the to form granules, by adding cohesive forces to diluent
Are binders used often?
No, must be used w/ care since tablets must disintegrate at some point
What are common binders used in wet granulations?
- Starch
- Pregelatinized starch
- Gelatin
- Polyvinylpyrrolidone
- Methycellulose
- Ethylcellulose
- Polyvinyl alcohols
What is the most common binder?
Starch (corn)
Starch is a good carrier for ____
Dyes
Is starch charged?
No
Is starch reactive?
No
Are additional excipients required w/ starch and why?
Yes b/c may give soft granules
____ is a stronger binder than starch
Gelatin
What are disadvantages to gelatin use as a binder?
- Tablets w/ gelatin harden over time
- Granules are quite hard, and gelatin must be added while hot, which leads to some problems (thermosensitivity and dissolution)
The use of gelatin has been replaced by _____
Synthetic polymers
What are 2 examples of natural gums?
Acacia and tragacanth
What is a problem w/ natural gums?
Bacterial contaminants
Is polyvinylpyrrolidone hydroscopic and what does this mean?
- Slightly
- Tablets don’t harden w/ time
In which solvents can polyvinylpyrrolidone be used?
Alcoholic and hydro-alcoholic solvents
Why are cellulose derivatives used as binders?
Good binding properties and very versatile
What are the most common cellulose derivatives used as binders?
- Methylcellulose
- Carboxymethylcellulose
- Ethylcellulose
- Hydroxypropylmethylcellulose
Why are lubricants used?
- To ease ejection of the tablet from the die
- To prevent sticking to the faces of the punches
- To reduce wear on tooling
Where are lubricants applied?
To coat the granules, therefore particle size of lubricant is important since we want uniform coating
What is the most common lubricant used?
Magnesium stearate
What is a disadvantage to magnesium stearate?
Slightly alkaline, may cause problems and tend to waterproof granules which may affect disintegration or dissolution properties of tablets
What are disintegrants?
Substances applied to granulation to cause tablet to break apart in aqueous environment
What is the ideal function of disintegrants?
Should cause the tablet to disrupt into the granules from which it was compressed, and then into the powder particles from which the granules were prepared
___ reverse the effect of a binder
Disintegrants
When are disintegrants external?
When added to the formed granules just prior to compressino
When are disintegrants internal?
When it is a component in the granulation mixture
How do disintegrants work?
By swelling or reacting w/ water to cause disruptive forces
Colorants are usually added to ____
Tablet formulation
Why are colorants used?
To increase elegance or for identification
Why are pastel shades often used as colorants?
Least likely to slow mottling
Why are colorants frequently used as lakes?
Less likely to bleed and better uniformity
What are the steps in wet granulation?
1) Milling of drug and excipients
2) Mixing of milled powders
3) Preparation of binder and wet mass
4) Screening of wet mass
5) Drying of granules
6) Screening dry granules
7) Mixing w/ lubricant
8) Tablet compression
What are the steps of dry granulation?
1) Milling of drug and excipient
2) Mixing of milled powders
3) Compression into slugs
4) Screening of slugs
5) Mixing w/ lubricant
6) Tablet compression
What are the steps of direct compression?
1) Milling of drug and excipient
2) Mixing of milled powders
3) Tablet compression
What is the ideal hardness of a granule?
Hard enough to withstand handling and shipping but must disintegrate and/or dissolve in specified time
What are the 2 types of tablet presses?
- Single punch
- Multi-station rotary press
When is a single punch tablet press used?
- Small batches
- Laboratory instrument in product dev’t
What is compression?
The process of pressing material to make it more firm and solid
What is the force pattern complex?
An axial force causing compression and a radial force exerted by the die wall
____ resists consolidation during compression
Frictional force btwn granule mass and die walls
Are forces distributed uniformly throughout a granule mass?
No, regions of high density occur at the periphery due to movement of the material in a radial direction and friction along die walls
What are the 2 events that occur in tableting process?
1) Reduction in bulk volume by elimination of air (compression)
2) Increase in mechanical strength of mass due to particle-particle interactions (consolidation)
What is needed for a tablet to form?
Sufficient bond formation during consolidation
What causes most of the problems in tableting?
Poor granulation
What are some common tableting problems?
- Binding or sticking
- Picking
- Capping
What is binding or sticking of a tablet?
Tablets ejected w/ difficulty often accompanied by grunting sound
What can cause binding or sticking of a tablet?
- Inadequate or uneven lubrication of granules
- Granules too dry or too wet
- Die dirty or scratched
- Worn die
What is picking of a tablet?
Granule material sticks to the punch faces, laving the tablet w/ a pitted surface
What can cause picking of a tablet?
- Inadequate or uneven lubrication of granules
- Granules under-dried
- Scratched or damaged punch face
What is capping of a tablet?
On decompression, top of tablet becomes detached
What can cause capping of a tablet?
- Worn tooling
- Compression speed too fast
- Excess fines
- Punch fits too tightly into die
- Excessive pressure
- Insufficient or ineffective binder
- Over-dried granules
- Crystal habit of drug may have changed
How is uniformity determined?
Weight variation if tablets are uncoated, tablets contain more than 50 mg of active drug, and if active component provides more than 50% of total weight
What if a tablet doesn’t meet the criteria for weight variation uniformity testing?
Content uniformity testing must be done
Describe the weight variation uniformity testing process
- Weight 10 tablets and calculate content of active ingredient in each based on assay results (assume homogenous distribution of drug)
- All tablets must contain 85-115% of labeled amount and relative standard deviation must not exceed 6%
- If one unit is outside these limits, a further 20 tablets are weight
When are the requirement for the weight variation uniformity test met?
If no more than one unit out of 30 is outside the 85-115% range and the RSD of the 30 tested does not exceed 7.8%
What happens if the tablets do not meet the criteria for the weight variation uniformity test?
Content uniformity done by assay of 10 units individually and proceed as normal
What does a disintegration test determine?
Time required for tablet to disintegrate in a specified test fluid at a specified temp
Can disintegration results be extrapolated to bioavailability?
No, so dissolution testing is usually required
What does the USP disintegration test consist of?
An apparatus into which 6 tablets are placed each into a cylindrical tube which is covered at the bottom by a 0.025 square inch wire screen
Describe the USP disintegration testing process
- Tubes are raised and lowered through a distance of 5.3-5.7 cm 29-32 times/minute
- Disintegration complete when no solid material w/ a palpable core remains on the mesh
- If one or two tablets fail, a further 12 tablets are tested
When the conditions met for the USP disintegration test?
No more than 2 of the 18 tablets fail
What does the USP dissolution test determine?
Time required for tablet to dissolve in a specified test fluid at a specified temperature
Does dissolution have a correlation to bioavailability?
Yes
What are the 2 types of apparatus’ used for dissolution tests
1) Apparatus consists of a 1000 mL glass vessel, a motor w/ a shaft and a cylindrical basket made of a metal screen (40 mesh)
2) Apparatus same except that a paddle is used in place of basket
What should the mesh be made of?
Stainless steel or gold plated
Describe the USP dissolution testing process
- Glass vessel is filled w/ fluid and held at the specified temp
- Tablet is placed into each basket or into the vessel if paddle is used
- Rotation speed and time required for dissolution are specified in monograph
- The quantity of drug which must be in solution w/in the time period is also specified in monograph
What does the USP friability test determine?
How a tablet will withstand handling and general wear and tear
What type of apparatus does the USP friability test use?
Apparatus w/ revolving drum which drops the tablet a specified distance a specified number of times
Describe the USP friability testing process
5-20 tablets are weighed, placed in the apparatus, tested, and then re-weighed
What is the requirement to pass the USP friability test?
Weight loss of no more than 0.8% after about 100 drops
What are the units for hardness?
kg or kN
How is hardness usually tested?
Tablet is placed on an anvil and force is transmitted to it by means of a moving plunger
What does tablet hardness determine?
Ability of tablet to withstand shocks during handling and shipping
What does hardness correlate w/?
Disintegration and dissolution
What is hardness a function of?
- Compression force during pressing
- Particle density and size
- Tablet shape
- Components of formulation
What is the usual minimum hardness for an uncoated tablet?
5 kg
What are the 3 categories of tablet coating?
- Sugar coating
- Film coating
- Compression coating
What are the 2 basic processes for applying coatings?
- Pan coating
- Air suspension coating
What are coatings used for?
- To mask unpleasant odors and taste
- To protect an ingredient from decomposition
- To improve product elegance
- May be used to control release rate or at a particular portion of GI tract
Good control over ____ is needed for sugar coating
Humidity, temp, and dust
What are the processes involved in sugar coating?
Sealing, subcoating, syruping, finishing, and polishing
Tablet cores usually represent about __% of weight of finished tablet
50%
How is film coating accomplished?
Deposition of one or more film forming polymers on surface of tablet
Usually film represents less than __% of finished tablet weight
5%
What qualities should film forming materials have?
- Soluble in solvent suitable for process and in GI fluids
- Form strong continuous film that is smooth and elegant
- Stable to heat, light, air, moisture, and drug in product
- Have no appreciable taste, odor, or color
- Able to support pigment or coating additives
- Non-toxic
- Crack resistant
Non-enteric coating materials are usually _____
Cellulose derivatives
Enteric coating materials are usually ____
Phthalate esters of cellulose
What are common solvents used for coating?
Alcohols, esters, chlorinated hydrocarbons, acetone, and other ketones
What occurs in compression coating?
Core is placed in center of larger die and surrounded w/ coating material in the form of free flowing granules, which is compressed into final product
Is compression coating common? Why or why not?
No b/c of equipment required
What can compression coating be used for?
- Incompatible drugs
- Repeat-action tablets where first dose is coating and second dose is slower disintegrating core
