2. INTRODUCTION
Tablet is defined as a compressed solid dosage
form containing medicaments with or
without excipients. According to the Indian
Pharmacopoeia Pharmaceutical tablets are
solid, flat or biconvex dishes, unit dosage
form, prepared by compressing a drug or a
mixture of drugs, with or without diluents
3. The advantages of the Tabletdosage
form are:
• Theyare unitdosage form and offerthegreatest
capabilitiesof all oral dosage form forthegreatestdose
precisionand the least contentvariability
.
• Cost is lowest of all oral dosageform.
• Lighterandcompact.
• Easiestand cheapesttopackageand strip.
• Easytoswallowing with leasttendency forhang-up.
• Sustained releaseproduct ispossible byentericcoating.
4. • Objectionableodourand bittertastecan be masked by
coating technique.
• Suitable for large scaleproduction.
• Greatest chemical and microbial stabilityoveralloral
dosageform.
• Product identification is easy and rapid requiring no
additional stepswhen employing an embossedand/or
monogrammed punchface.
5. Disadvantages of Tablet dosage formare:
• Difficulttoswallow incaseof childrenand unconscious
patients.
• Somedrugsresistcompression intodensecompacts,owing to
amorphous nature, lowdensitycharacter.
• Drugswithpoorwetting, slowdissolution properties, optimum
absorption high in GIT may bedifficult to formulateor
manufacture as a tablet that will still provide adequate or full
drug bioavailability.
• Bittertestingdrugs, drugswithanobjectionableodorordrugs
that are sensitive to oxygen may require encapsulation or
coating. In such cases, capsule may offer the best and lowest
cost.
6. Different types of Tablets
(A) Tablets ingested orally:
1. Compressed tablet, e.g. Paracetamol tablet
2. Multiplecompressed tablet
3. Repeatactiontablet
4.Delayed release tablet, e.g. EntericcoatedBisacodyl
tablet
5. Sugarcoated tablet, e.g. Multivitamintablet
6. Film coated tablet, e.g. Metronidazoletablet
7. Chewable tablet, e.g. Antacidtablet
(B) Tablets used in oralcavity:
1. Buccal tablet, e.g. Vitamin-ctablet
2. Sublingual tablet, e.g. Vicks Mentholtablet
3. Troches orlozenges
4. Dental cone
7. (c) Tabletsadministered byotherroute:
1. Implantationtablet
2. Vaginal tablet, e.g. Clotrimazoletablet
(D) Tabletsused to preparesolution:
1. Effervescenttablet, e.g. Dispirintablet (Aspirin)
2. Dispensing tablet, e.g. Enzymetablet (Digiplex)
3. Hypodermictablet
4. Tablettrituratese.g. Enzymetablet(Digiplex)
15. • 1. Diluent: Diluents are fillers used to make required bulk
of the tablet when the drug dosage itself is inadequate to
produce the bulk. Secondary reason is to provide better
tablet properties such as improve cohesion, to permit use of
direct compression manufacturing or to promote flow. A
diluentshould have following properties:
1. They must be nontoxic
2.Theymust becommerciallyavailable inacceptable
grade
3. Therecost must below
4. They must be physiologicallyinert
5.Theymust bephysically & chemicallystable by
themselves & in combination with thedrugs.
6. They must be free from all microbialcontamination.
7. Theydo notalterthe bioavailabilityof drug.
8. They must becolorcompatible.
17. 2. Binders and Adhesives: These materials are
added eitherdryorinwet- form to formgranules
orto formcohesivecompacts fordirectly
compressed tablet.
• Example: Acacia, tragacanth- Solution for 10-25%
Conc.
• Cellulose derivatives- Methyl cellulose, Hydroxy
propyl methyl cellulose, Hydroxypropyl cellulose
• Gelatin- 10-20% solution
• Glucose- 50% solution
• Polyvinylpyrrolidone (PVP)- 2% conc.
• Starch paste-10-20% solution
• Sodiumalginate
• Sorbitol
18. 3. Disintegrants: Added to a tablet formulation to
facilitate its breaking or disintegration when it
contact in waterin theGIT.
• Example: Starch- 5-20% of tabletweight.
• Starch derivative – Primogel and Explotab(1-8%)
• Clays- Veegum HV
, bentonite 10% level incolored
tabletonly
• Cellulose
• Cellulosederivatives- Ac- Di-Sol (sodiumcarboxy
methyl cellulose)
• Alginate
• PVP (Polyvinylpyrrolidone), cross-linked
19. • Superdisintegrants: Swellsup toten foldwithin
30 secondswhen contactwater.
• Example:
cellulose,
(polymer),
Crosscarmellose- cross-linked
Crosspovidone- cross-linked povidone
Sodium starch glycolate- cross-linked
starch. Thesecross-linked products swellswith in30
secondswhen incontactwithwater
.
• A portion of disintegrant is added
granulation and a portion
before
before
compression,whichserveas glidantsorlubricant.
20. • 4. Lubricant and Glidants: Lubricants are intended to
prevent adhesion of the tablet materials to the
surface of dies and punches, reduce inter particle
friction and may improve the rate of flow of the tablet
granulation.
Glidants are intended to promote f low of granules or
powder material by reducing the friction between the
particles.
• Example: Lubricants- Stearic acid, Stearic acid salt -
Stearic acid, Magnesium stearate, Talc, PEG (Polyethylene
glycols), Surfactants
• Glidants- Corn Starch – 5-10% conc., Talc-5% conc., Silica
derivative - Colloidal silicas such as Cab-O- Sil, Syloid,
Aerosil in 0.25-3%conc.
21. • 5. Coloringagent: Theuseof colorsand dyes ina
tablet has threepurposes:
(1) Masking of off colordrugs
(2) Product Identification
(3) Production of moreelegantproduct
• All coloring agents must be approved and certified by FDA.
Two forms of colors are used in tablet preparation – FD &C
and D & C dyes. These dyes are applied as solution in the
granulating agent or Lake form of these dyes. Lakes are
dyes absorbed on hydrous oxide and employed as dry
powdercoloring.
• Example: FD & C yellow 6-sunset yellow,FD & C yellow 5-
Tartrazine ,FD & C green 3- Fast Green,FD & C blue 1-
Brilliant Blue ,FD & C blue 2 - Indigocarmine
23. Lactose
• Non-reactive in anhydrous or hydrousform
• Hydrous form undergoes maillard reaction leading
to browning and discoloration of certain drugs,
hence anhydrous form ispreferred
• Butanhydrous formpicksup moisturewhenexposed to
humidity.
• Inwetgranulation, hydrous lactoseof twovarietiesare
used 60-80 mesh (coarse) and 80-100 mesh (regular)
grade.
• Lactose formulationshowgoodrelease.
• Low costdiluent
• But maydiscolor inpresenceof aminedrug basesorsalts of
alkalinecompounds
24. Spray dried lactose
Lactose is placed in aqueous solution,removed
impurities and spraydried
Mixture of large alpha monohydrate crystals and
spherical aggregates of smallercrystals
Good flowability but less compressibility
Poor dilutionpotential
Less compressibility upon initialcompaction
Problem of browning due to contamination of 5-
hydroxyfurfural which was accelerated in the presence
of basic amine drugs and catalyzed by tartarate, citrate
and acetate ions
25. – Fast-Flow lactose (early1970s)
• Spherical aggregates of microcrystalslactose
monohydrate
• Held togetherbya higherconcentrationof glass
(amorphous lactose)
• Much morecompressible
• Highlyfluid
• Non hygroscopic
• Tabletsarethreetofourtimesharderthanregular
spraydried
– Tabletose: aggromerate formof lactose
• Morecompressible thanspraydried but less
compressible than Fast Flolactose
26. Starch
• Can becorn, wheatorpotatosource
• USPgradeof starch haspoorflow & compression
characteristics
• Also has high moisturecontent between between 11 &14
%.
• Speciallydried starchesalso havestandard moisture level
of 2-4%
• Therefore used inwetgranulation
27. Sta 1500:
• Intactstarchgrainsand rupturedstarchgrains that
havebeen partiallyhydrolyzed
and subsequentlyaggromerated
• Free f lowing, self lubricating, containingslightly
high MC (10 %)
• Duetowhichdoes notform hard compacts
• Dilutionpotential is minimal, notgenerallyusedas
filler-binder butas fillerdisintegrant
• Retainsthedisintegrantpropertiesof starchwithout
increasing the fluidity and compressibility of the
total formulation
• Flowpromoters likecolloidal silicondioxide is
needed.
• Lubricants tend todramaticallysoften tablets
containing high concentrationsof Starch1500
28. Dextrose
90-92% dextrose, 3-5% maltoseand theremainder
higherglucosepolysaccharides
Available both anhydrousand a hydrateproduct
Excellentcompressibilityand goodf low
Contain 8-10% moistureand may increasehardness
aftercompression
Largest particlesize, therefore blending problemmay
occur
Cerelose isalsoavilable
29. Cellulose
– Microcrystallinecellulose(Avicel)
Derived fromaspecial gradeof purifiedalphawood
cellulose bysevereacid hydrolysis to remove the
amorphous cellulose portions, yielding particles
consisting of bundlesof needlelike microcrystals
• PH101 powderand PH102 arethetwogrades
available.
• mostcompressiblewith Highestdilutionpotential
• Astrong compact formed due tostrong hydrogen
bonds ,and ruptured due to passageofwater
• Extremely low coefficientof friction, nolubricant
• Notused as only fillerbecauseof itscostand
density,
• used in theconcof 10-25%asa filler-binder-
disintegrant,
31. Powders intended for compression into tabletsmust
possess two essential properties
Powderf luidity orf lowability
• The materialcan betransported throughthe hopperintothe
die
• T
oproducetabletsof aconsistentweight
• Powderflowcan be improved mechanicallybytheuseof
vibrators, incorporatetheglidant
Powdercompressibility
• Thepropertyof formingastable, intactcompactmasswhen
pressure isapplied iscalled powdercompressibility
Easily mixedwithotherparticles
Homogenouscolouringetc
Frictionand adhesionproperties
32. Slugging (dry granulation):
a. Blend is forced intodiesof largecapacitytablet pressand compacted using flat
facedpunches.
b. compacted massesarecalled slugsand process is calledslugging.
c. Slugs milled orscreened toproducegoodfree flowing granules for compression.
33. Dry compaction/Rollercompaction
Ona largescalecompressiongranulationcanalso be
performed on a rollercompactor.
Granulation by dry compaction can also be achieved by
passing powders between two rollers that compact the
materialatpressureof upto 10 tonsperlinearinch.
Materials of very low density require roller compaction to
achieve a bulk density sufficient to allow encapsulation or
compression.
One of the best examples of this process is the
densification of aluminumhydroxide.
Rollercompactor iscapableof producing as muchas 500
kg/hr of compacted ribbon like materials which can be
thenscreened and milled in togranules forcompression.
34. Limitations of drygranulation
1 Dry granulation often producesa higherpercentageof
fines or non compacted products, which could
compromisethequalityorcreateyield problems forthe
tablet.
2 Itrequiresdrugsorexcipientswithcohesiveproperties.
35. Wetgranulation
The most popular method (over 70%)
Granulation isdone
T
opreventsegregation of theconstituents of thepowder
blend.
Toimproveflowability of the powdermixture.
T
oimprove thecompaction characteristics of thepowder
mixture due to better distribution of the binder within
thegranules.
T
oimprove homogeneityand thusensurecontent
uniformity
Wetgranulation isaprocessof using asolution bindertothe
powder mixture. Theamountof liquid can be properly
managed; overwetting = thegranules to betoo
hard, underwetting =too soft andfriable.
Aqueoussolutions aresafer thanothersolvents.
36. Procedure of WetGranulation
Step 1: Weighing and Blending
Step 2: wetgranulate prepared byadding the bindersolution
Step3: Screening thedampmass intopelletsorgranules (6-
8mesh)
Step 4: Drying thegranulation in thermostaticallycontrolled
ovens
Step 5: Dryscreening:
Step 6: Mixing with other ingredients: Adry
lubricant, antiadherentand glidant isadded to the
granuleseitherbydusting overthespread-outgranulesor
by blending with thegranules. Dry binder, colorantor
disintegrant may bealsoadded in thisstep.
Step7: Tableting: Laststep inwhich thetablet is fed intothe
diecavityand thencompressed.
37. Limitations of wetgranulation:
1 Multipleseparatesteps areinvolved.
2 Notsuitableforheatand moisturesensitivedrugs
Equipments
Traditionally,dry mixing in wetgranulation process
has been carried outusing,
Sigma blade mixer,
Heavy-duty planetarymixer.
38.
39. List of equipments used ingranulation
High Sheargranulation:
i)Little ford Lodgiegranulator
ii)Little ford MGT granulator
iii)Diosnagranulator
iv)Gral mixer
Granulatorwithdryingfacility:
i) Fluidized bed granulator
ii) Day nauta mixerprocessor
iii) Doubleconeortwinshell processor
iv) T
opogranulator
Special granulator:
i) Rotogranulator
ii) Marumerizer
40. Compression
Tableting procedure
Filling
Compression
Ejection
Tabletcompression machines
• Hopper for holding and feeding granulationto be
compressed
• Diesthatdefinethesizeand shapeof thetablet
• Punches forcompressing thegranulationwithin thedies
• Camtracks forguiding the movementof thepunches
• Feeding mechanisms formoving granulation fromthe
hopper into thedies
41. • Single punchmachine
• Multi-station rotarypresses
• The head of thetabletmachinethatholdstheupper
punches,diesand lowerpunches in placerotates
• As the head rotates, the punches are guided up and
down byfixed cam tracks,whichcontrol thesequence
of filling, compressionandejection.
• The portionsof the head that hold the upperand
lowerpunchesarecalled theupperand lowerturrets
• Theportion holding thedies iscalled thedietable
42. Compressioncycle
• Granules from hopperempty in thefeed frame (A)
containing several interconnected compartments.
• Thesecompartmentsspread thegranulationoverawide
areatoprovidetimeforthedies (B) tofill.
• Thepull down cam (C) guidesthe lowerpunchestothe
bottom, allowing thedies tooverfill
• The punches then pass overaweight-control cam
(E), which reduces the fill in thediestothedesired
amount
• A swipe off blade (D) at the end of the feed frame removes
the excess granulation and directs it around the turret and
back into the front of the feedframe
• Thelowerpunchestraveloverthe lowercompression roll
(F) while simultaneously the upper punches ride beneath
the uppercompression roll(G)
43. • The upperpunchesenter a fixed distance into the
dies, whilethe lowerpunchesareraised tosqueezeand
compact thegranulationwithin thedies
• Afterthe momentof compression, the upperpunches are
withdrawnas theyfollowtheupperpunchraising cam (H)
• Thelowerpunchesrideupthecam (I) which bringsthe
tabletsflushwithorslightlyabove thesurfaceof thedies
• The tabletsstrikea sweepoff blade affixed to the front of
thefeed frame (A) and slidedown achute intoareceptacle
• Atthesametime, the lowerpunchesre-enterthepull
down cam (C) and thecycle isrepeated
44.
45.
46. • The principle modification from earlierequipment has
beenan increase in production ratewhich isregulated by
– Numberof tooling sets
– Numberof compressionstations
– Rotational speed of thepress
Multirotary
machine
High speed
rotarymachine
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58. Processing problems
• Capping is the partial or complete separation of the
top or bottom crowns of a tablet from the main body
of thetablet.
• Lamination isseparationof atabletintotwoormore
distinct layers. Both of these problems usually result
from airentrapmentduring processing.
• Picking isremovalof atablet’ssurfacematerial bya
punch.
• Sticking is adhesion of tablet material to a die wall.
Thesetwoproblemsresultfromexcessivemoistureor
substances with low melting temperatures in the
formulation
59. • Mottling isan unequalcolordistributiononatablet,with
lightordark areasstanding onotherwiseuniformsurface.
Thisresults from useof adrug withacolordifferent from
thatof the tabletexcipients or from adrug with colored
degradationproducts.
• Weightvariation-granulesizedistribution,poor
fiow,punchvariation
• Hardnessvariation
• Double impression-monograms orengraving onpunch
