Unit Dose Operations of Solid Dosage

Form

Crystallization Milling Blending Granulation

/drying

Compression Coating Packaging

PLAY
 Learning objectives:
• Different methods to manufacture tablets
 Tablet production
• Powders intended for compression
into tablets must possess two
essential properties
– Powder fluidity
• The material can be transported through
the hopper into the die
• To produce tablets of a consistent weight
• Powder flow can be improved mechanically
by the use of vibrators, incorporate the
glidant
– Powder compressibility
• The property of forming a stable, intact
compact mass when pressure is
applied
 Three Principle Methods
• Direct Compression
– Blending the dry powdered ingredients
together, and then compressing into tablets.
• Wet Granulating
– A pharmaceutical glue called a binder is put
into water or a solvent solution and is sprayed
or metered into the powders.
• Dry Granulating
– Use mechanical force to densify and compact
powders together which forms dry granules.
 Process route for Tablet Manufacture
Direct Compression Dry Granulation Wet Granulation
 Manufacturing steps for direct
compression
Direct compression involves comparatively few
steps:
i) Milling of drug and excipients.
ii) Mixing of drug and excipients.
iii) Tablet compression.
 Direct compression
• NaCl, NaBr, KCl, are directly compressible (DC)
• DC may produce tab that do not disintegrate
• Addition of disintegrant can interfere with
compressibility
• Material with film of adsorbed gas hinder
compaction
• DC diluent is an inert subs that may be
compacted with little difficulty and may compress
even when quantities of drugs are mixed with it.
 Limitations of direct compression
• Difference in particle size and bulk density
between dry granules may lead to stratification
within the granules, poor drug content uniformity
esp with low dose drug
• Large dose drug- does not compress by itself–
large quantity of diluent – tab difficult to swallow
• Certain DC material react eg. Spray dried
lactose with amines
• Because of dry nature static charge may build up
which prevents uniform mixing.
 Granulation
WHY GRANULATE?

• To improve powder flow.

• To improve compressibility.
• To reduce fines.
• To control the tendency of powders to segregate
• To control density , particle hardness.
• To capture and fuse small quantities of active
material.
• Produce uniform blend
 Dry granulation
• Resistant to compression when prepd by
wet granulation
• Effective dose of drug is too high for direct
compression
• Two methods

slugging Roller compactor(chilsonator)

 Roller compactor
• Capacity 500kg
• Utilize two rollers that revolve towards each other
• Compaction force depends on
*pressure exerted on rolls
*rotational speed of rolls
*rotational speed of feed screws
• Horizontal screw – picks powder from hopper & maintains continuous flow
to vertical screw.
• Vertical screw:function
*delivers powder to rolls
*deareates powder &maintains constant flow
• Advantage over slugging –
*Increased production capacity
*Greater control of cimpaction pressure/dwell time.
*No need of excessive lubrication
• Torsades de pointes
 Granulation mechanism
Particle bonding mechanism
• Adhesion and cohesion forces in the immobile liquid films between
individual primary powder.
• Interfacial forces in mobile liquid films within the granules.
* pendular state
* funicular state
* capillary state
• the formation of solid bridges after solvent evaporation
* partial melting
* hardening binders
* crystallization of dissolved substances
• Attractive forces between solid particles
• Mechanical interlocking
 Mechanisms of granule formation
1. Nucleation: particle -particle contact and
liquid bridges.
2. Transition- growth of nuclei

Single particles added Two or more nuclei combine

 3. Ball growth:
a) coalescence- two or more granules form large
granules
b) Breakage- granules break into fragments
c) Abrasion transfer- agitation of granule bed
leads to attrition of materials from granules,
this adheres to other granules
d) Layering- second batch of powder ,mix is
added to the bed of granules, it forms a layer
on surface of granules thereby increasing the
size.
 Classification of wet granulators

Without dryers
Littleford lodige With dryers
mixer FBD
Diosna mixer Day nauta
granulator Topogranulator
Littleford MGT CF granulator
GRAL mixer Double cone
granulator twinshell blender
Oscilating Roto granulator
granulator
 GRAL MIXER/GRANULATOR
• Modification of planetary mixer
• A large mixing arm shaped to rounded
configuration of the bowl provides large
scale mixing
• Small chopper blade enters off center from
the mixing arm
• Mixing bowl loaded at floor level
• Raised to moxing position by hydraulic
bowl elevator cradle
• Tight seal between bowl & cover
• Discharge in raised position offering suff.
Space for a container to be placed
beneath discharge port
• Cleanup easier as main mixing blade is
not a part of the bowl
 Diosna mixer granulator
• Bowl mounted in vertical position
• High speed mixer blade revolves around bottom
• At side is chopper blade-high speed-breaks
lumps(1750-3500)
• 3 openings on the lid—
Spray nozzel , air exhaust , view port
Total time required: 11 min
Mixing: 2 min, granulation: 8 min, discharge:1 min