Transcript Dry granulation

TABLETS
By K . Madhuri
Ist M.Pharmacy
pharmaceutics
UNDER THE GUIDANCE OF
DR. A.SEETHA DEVI
M.PHARM., PHD.,
INTRODUCTION
DEFINITION
•
Tablet is defined as a compressed unit solid
dosage form containing medicaments with or
without excepients.
or
Tablet represent unit
dosage form in which
one usual dose of the
drug has been accura
tely placed.
ADVANTAGES
• Cost is lowest of all oral dosage forms.
• Lighter and compact.
• Greatest dose precision and the least content
variability.
• Easy to swallowing with least tendency for hang-up.
• Easiest and cheapest to package and ship.
DISADVANTAGES
• Difficult to swallow for children or unconscious
patients.
• Some drugs resist compression in to dense
compacts.
• Drugs with poor wetting , slow dissolution
properties, may be difficult to formulate a tablet.
• Bitter taste drugs , drugs with an objectionable odor .
In such cases , the capsule may offer the best and
lowest cost approach.
PROPERTIES OF TABLETS
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Should be an elegant product.
Should have the strength.
Should have the chemical and physical stability.
Must be able to release the medicament.
Must have a suitable chemical stability over time so as
not to allow alteration of the medical agent.
A . TABLETS INGESTED ORALLY
1 . COMPRESSED TABLETS
2 . MULTICOMPRESSED TABLETS
4 . Sugarcoated tablets
5 . Film coated tablets
B . Tablets used in oral cavity
1 . Sublingual tablet
2 . Troches or lozenges
Tablets administered by other routes:
• Implantable tablets : These are designed for
subcutaneous implantation in animals or man.
• To provide a constant drug release rate.
• Small , cylindrical or rosette-shaped forms.
• Length is not more than 8mm.
• Vaginal tablets : These are designed to undergo slow
dissolution and release in the vaginal cavity.
• Ex : Clotrimazole tablets.
Tablets used to prepare solutions:
1 . Effervescent Tablets
2 . Hypodermic Tablets
3 . Dispensing tablets
4 . Tablet triturates
Techniques for granulation
• Direct compression : Blending the dry powdered
ingredients together , and then compressing in to
tablets.
• Wet granulation : A pharmaceutical glue called a
binder is put in to water or a solvent system and
is sprayed or metered in to powders.
• Dry granulation : Use mechanical force to densify
and compact powders together which forms dry
granules.
Wet granulation
Wet granulation is a process of using a liquid
binder to lightly agglomerate the powder mixture. The
amount of liquid has to be properly controlled, will cause
over-wetting will cause the granules to be too hard and
under-wetting cause them to be too soft and friable .
Aqueous solutions have the advantage of being safer to deal
with than solvent-based systems but may not be suitable for
drugs which are degraded by hydrolysis.
• In this process , powder is fed to a product container
and then moistened or sprayed with molten material in
order to increase the cohesive forces.
• The liquid can be water or an organic solvent , if
necessary with binder.
• At the same time , the ingredients are mixed together
vigorously.
Dry granulation
• Dry granulating, also called Slugging, Chilsonating or
Roller compaction, involves the pressing of mixed
powders into an object to be reground into a precise
powder. This action increases particle density, improves
powder flow and captures fines.
• Powders can be compacted using a tablet press; this is
called Slugging. Once slugging is completed or powders
are compacted on a Chilsonator or Roller Compactor,
they are milled.
The dry granulating method is used over other
technologies for one or more reasons :
• Granulating materials which are sensitive to heat and or
moisture.
• Produce a uniform particle size range.
• Improve flow properties.
• Control dust.
• Control bulk density.
• Produce uniform blends.
• Control particle hardness.
• Improve wetting or dissolution rates.
Direct compression
•In early days, most of the tablets require granulation of
the powdered Active Pharmaceutical Ingredient (API) and
Excipients. At the availability of new excipients or
modified form of old excipients and the invention of new
tablet machinery or modification of old tablet machinery
provides an ease in manufacturing of tablets by simple
procedure of direct compression.
• Among the tehniques used to prepare tablets , direct
compression is the most advanced technology.
• It involves only blending and compression.
• Thus offering advantages particularly in terms of speed
production.
• Because it requires fewer unit operations , less
machinery , reduced number of personnel ,
considerably less processing time along with
increased product stability.
Limitations
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Stratification – poor content uniformity.
Interaction.
Large dose drugs (30%).
Static charge.
Different punches
PROCESSING PROBLEMS OF
TABLETS
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Capping and Lamination
Picking and Sticking
Mottling
Weight variation
Hardness variation
Drug instability
Double impression
CAPPING AND LAMINATION
Capping:
Partial or complete separation of the top or
bottom
crowns of a tablet from its main body.
Lamination:
Separation of tablet into two or more distinct
layers.
Reasons:
• Air entrapment among the particles or granules .
• Over drying of granules.
• Deep concave punches.
• Incorrect setup at the press.
Remedies:
• Use of sufficient amount of binder.
• Use of proper amount of fines .
• Use of sorbitol, methylcellulose, or PEG 4000.
• Use of flat punches.
• Maintaining the compression machine in a proper
condition.
PICKING AND STICKING
Picking:
Adhering to and removal of tablet material by the punch surface.
sticking:
Adhering of tablet material to die wall.
Reason:
 Improperly dried granulation
 Inclusion of high quantity of low melting point substances, either active ingredients
or additives such as stearic acid, Polyethylene glycol.
 Use of punches with improper faces.
Remedies:
allowing the granulation to dry sufficiently.
 Adding an adsorbent i.e., silica aerogel,
aluminium
 Decreasing the moisture content of the
granulation, hydroxide, and MCC.
MOTTLING
 Mottling is an unequal distribution of color on a tablet, with
appearance of light and dark areas on it.
Reason:
 Use of drug whose color differs from that of the tablets
excipients.
 Use of drugs whose degradation products are colored.
 Migration of dye to the surface of granulation during drying.
 Improper mixing of dye in direct compression formulations.
Remedies:
 Changing the solvent system, reducing the drying
temperature.
 Dye should be mixed properly.
WEIGHT VARIATION:
 Weight of a tablet being compressed is determined by
the amount of granulation in the die prior to compression.
Reasons:
 Granule size and size distribution before compression:
Variations in the sizes of granules.
 Poor flow:
The process of die filling process depends on uniform flow of
granules from the hopper.
Disadvantages of poor flow:
Arching or bridging
Rat holing
 Arching is segregation of fine particles at the neck of
hopper.
 Rat-holing is segregation at sides of the hopper.
Remedies to overcome poor flow:
 Using of high amount of glidants such talcum, colloidal
silica.
 Using of induced die-feeders.
but these may cause reduction in granule size.
Poor mixing:
Improper distribution of lubricants and glidants.
Remedy:
Carry out mixing for 3min, but excess mixing during lubricant
addition results in granule friability.
Punch variation:
Unequal length of lower punchs.
Remedy:
Using of tooling set with uniform dimensions.
HARDNESS VARIATION:
Hardness depends upon weight of material and the space
between upper and lower punches at the movement of
compression.
DRUG INSTABILITY:
If granules are not properly dried, and if drug is moisture
sensitive then drug become unstable.
DOUBLE IMPRESSION:
 This problem arises when either lower or upper punches
having the monogram.
 In tablet compression machines, the lower punch is free
and rotates before the tablet is pushed off, resulting in double
impression.
Evaluation of tablets
General appearance
1. Size and shape
2. Unique identification markings
3. Organoleptic properties
4. Hardness
5. Friability
Drug content and release
1. Weight variation
2. Content uniformity
3. Disintegration test
4. Dissolution test
REFERENCES:
 Pharmaceutical Dosage forms: TABLETS VOLUME 1
 Pharmaceutical Dosage forms: TABLETS VOLUME 3
 The Theory and Practice of Industrial Pharmacy by
LEON LACHMAN, HERBERT A.LIEBERMAN,
JOSEPH L.KANIG
 BENTLEY’S Textbook of Pharmaceutics. Edited by
E.A.RAWLINS