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Tablets - Coggle Diagram
Tablets
Functional Excipients
Diluents/Fillers
What are diluents?
Inert bulking agents added to actives to make a
reasonably sized tablet.
Not to be confused with diluents for liq preparations which are used to dilute the preparation to a suitable concentraion.
In powders, diluents are used to dilute the active powder drug
Examples: Dextrose, dicalcium phosphate, α-lactose monohydrate, mannitol, microcrystalline cellulose, NaCl, sucrose
Binders
Used as
adhesives
to
bind powder in wet granulation
,
give strength
to compacts during compression
Examples: Natural gums (acacia, tragacanth), cellulosic derivatives, glucose, polyvinyl pyrrolidone (PVP), starch mucilage, pre-gelatinized starch, sodium alginate
Disintegrants
Promote
rapid breakup of tablets
to
increase surface area
and
aid drug dissolution
. Work via many mechanisms e.g. swelling or capillary action.
Examples: Alginic acid and alginates, MgAl silicate, sodium carboxymethyl
cellulose, starch, cross-linked PVP
Lubricants
Examples: talc,
Mg stearate
, stearates, stearic acid, liq paraffin,
sodium lauryl sulfate (SLS)
,
PEG 6000 (used more in powders)
SLS usually used tgt with Mg stearate
: Mg stearate is not hydrophobic, thus doesn’t dissolve readily in the body. SLS is not a very good lubricant, but has good wetting ability and improves hydrophilicity of formulation. Thus tablet dissolves and releases active more readily with combi of SLS + Mg stearate, than use of Mg stearate alone.
Talc and Mg stearat
e: more effective as
punch lubricants
;
Stearic acid
: more effective as
die lubricant.
Mg stearate
reduces tablet strength, prolongs disintegration.
Prevent the adherence
of granules to the punch and die faces of tablet press; facilitate flow of granules
Glidants
Improve flow properties of granulation by reducing inter-particulate friction. Can also improve packaging properties of powders.
Examples: silica, talc, starch
Manufacturing
Parameters to consider
Flowability
= ease of material flow from tablet hopper to tablet press.
How to improve flowability:
Use force feeders (mechanical method)
Add glidants (e.g. silica, talc)
Why is it important? Inadequate flow may result in arching, bridging, or rat-holing in hoppers.
Compressibility
: make powders compact, and not fall apart during storage and before ingestion
Methods
Dry Methods
Direct compression (DC)
Limitations
Dependent on the
fluidity and compressibility
of a tablet
diluent
, thus cannot be used for low potency, high dose actives. Will probably result in very large tablets.
Necessary to have
within-batch and batch-to-batch consistency
(due to properties of constituent particles remain unchanged)
Possible
segregation
of constituents may occur even after homogeneous blending all ingredients. Segregation occurs due to difference in particle size between ingredients, which may occasionally happen.
Need for
DC diluents
but they
cost more
than conventional diluents. Using conventional diluents may result in tablet falling apart.
Regulatory considerations is a lengthy and expensive process, thus DC usually used for generic drugs, when patent has already expired.
Unable to mask minor changes in physical properties
of the active ingredient, unlike wet granulation.
Use directly compressible excipients
Mix all excipients with drug together in a blender
Compress mixture directly on tablet press
Advantages
Simple
thus
cheap
(few steps, few equipment, thus lower cost, processing time, & power consumption)
Reduced risk of deterioration
of components (dry procedure, thus exposure to water and the high temperatures are avoided)
Disintegration of tablets into their primary particles
rather than granular aggregates. Thus, increased SA for dissolution in body, thus faster drug release.
Dry granulation (aka precompression/ slugging)
Used for moisture or heat sensitive
actives.
Powder blends are compressed into compacts/slugs or squeezed into solid cake between roller compacts
Compacts/slugs are milled and screened, producing granules with improved flow
Wet Methods
Wet granulation
What is
granulation
?
enlargement of particle size + increasing bulk density + improving flowability + increasing compressibility
i.e. Make powders "bigger" and "denser"
Advantages
Expertise and equipment
for wet granulation is
widely available
(e.g. High-speed mixer-granulators, fluidized bed granulation and drying), thus more
efficient and cost-friendly
Improves
flow and cohesion
of preparation
Reduces dust and cross-contamination
Powder blend handled
without loss of homogeneity
(i.e. no segregation)
Limitations
Many equipment
involved in multi-step process
Longer process
than DC
More machinery, equipment, manpower and thus cost involved
Binder choice and method of addition
Since wet granulation involved water, preparations need
time to dry
. Can be sped up by heating, but must take into consideration the
drug stability
(upon heating and drying) and its
distribution
within solid mass.
Process:
Mix active ingredient + diluent
Add binder + water (wetting)
Granulation
Drying
Sieving (to achieve consistent size)
Mix lubricant + glidant + disintegrating agent
Compression
Quality Control/ Stability Testing
Preparations exposed to different
environmental conditions
, can determine exp date
Tablet
appearance
: tab must look presentable
Tablet
hardness
: tab must meet certain criteria
Friability test: tests how friable (strong/breakable) tabs are.
Friability = "strength" of tablet
. Wetter tablets are less compressible, thus more friable.