UNIT- II Tablets. INDUSTRAIL PHARMACY-I

Ideal characteristics of tablets
Advantages and Disadvantages
Classification of tablets.
Excipients, Formulation of tablets.
Granulation methods,
Compression, and processing problems.
Equipment and tablet tooling.

1. UNIT-II
by Mr. MadhavB.Korde
AssistantProfessor
NAGPUR COLLEGE OF PHARMACY, NAGPUR. MH.

2. ✓Introduction
✓Ideal characteristics of tablets
✓Advantages and Disadvantages
✓Classification of tablets.
✓Excipients, Formulation of tablets.
✓Granulation methods,
✓Compression, and processing problems.
✓Equipment and tablet tooling.
CONTENT

3. Introduction
❑Tabletsaresolidunitdosageformofmedicamentswithorwithoutsuitable
diluents(excipients)andpreparedeitherbymouldingorcompression.
❑Solid,flat,orbiconvexdiscsinshape,size,andweight.
❑Variationinhardness,thickness,disintegration,anddissolutioncharacteristics.
❑AccordingtotheIndianPharmacopoeia,pharmaceuticaltabletsaresolid,flator
biconvexdiscs,unitdosageform,preparedbycompressingdrugsoramixture
ofdrugs,withorwithoutdiluents.
❑70%oftotalmedicinesdispensedintabletform.
❑Availableforallmedications,exceptfordifficultformulationoradministration.

4. Introduction

5. IdealCharacteristicsofTablets
1.Itshouldbeattractivehavingitsownidentity.
2.Itshouldbefreefromdefectssuchascracks,chips,contamination,
discoloration,etc.
3.Chemicallyandphysicallystableforlong-termintegrity.
4.Preventsalterationinchemicalandphysicalproperties.
5.Canwithstandmechanicalshocksduringproduction,packaging,
shipping,anddispensing.
6.Releasesmedicamentsinthebodyinapredictable,reproducible
manner
Introduction

6. Advantages
1.Simplestoraldosageform.
2.Provideaccurate,stabledoseswiththegreatestprecisionandleastcontentvariability
3.Easytouse,handle,andcarry.
4.Attractiveandpleasinginappearance.
5.Moststabledosageformintermsofphysical,chemical,andmicrobiologicalattributes.
6.Lowmanufacturingcostandhighmanufacturingspeed.
7.Easyandcheappackagingandshipping.
8.EasytoadministerandDispensing.
9.Sugarcoatingcanmasktheunpleasanttasteandodourofmedicaments.
10.Lessincompatibilitiesandenvironmentaldeteriorationduetotablets.
11.Dividetabletsintohalvesandquartersforfractionaldoses.
12.Moresuitableforlarge-scaleproduction.
13.Provideaccurateadministrationofevenminutedoses.
14.Easyidentificationduetothevarietyofshapesandcolors.
15.Formulatedwithspecialreleaseprofileproducts.
16.Economicalduetolowestcostcomparedtootheroraldosageforms.
Introduction

7. disAdvantages
1.Amorphousdrugsandlow-densitydrugsarechallengingtocompressintotablets.
2.Hygroscopicdrugsarenotsuitablefortablets.
3.Drugswithpoorwettingproperties,slowdissolution,andhighoptimal
absorptionarechallengingtoformulate.
4.Bittertasteandobjectionableodourrequirespecialtreatment,increasing
productioncosts.
5.Drugssensitivetooxygenmayrequirespecialcoatingandpackaging.
6.High-dosedrugsaredifficulttoformulateastablets.
7.Liquiddrugsarechallengingtoformulate.
8.Swallowingtablets,especiallybychildrenandcriticallyillpatients,is
challenging.
Introduction

8. Classification of Tablets
Tablets Ingested Orally
1.Compressed tablet.
2.Multiple compressed
tablets or press-
coated tablets.
3.Multilayered tablet.
4.Sustain released
tablet.
5.Enteric-coated tablets
6.Sugar-coated tablets
7.Film-coated tablet
8.Chewable tablets
Tablets used
in the Oral
Cavity
1. Buccal tablets
2. Sublingual
tablets
3. Lozenge
tablets
&Troches
Tablets used to
Prepare
Solutions
1.Effervescent
2.Dispensing
tablets
3.Hypodermic
tablets
4.Tablet
Triturate
Tablets
administered
by other
routes
1.Implants,
2.Vaginal tablets
(Inserts)

9. Classification of Tablets
1.Tablets Ingested Orally
I.CompressedTablets:
✓Thesetabletsareuncoatedandmadebycompressionof
Granules.Thesetabletsareusuallyintendedtoproviderapid
disintegrationanddrugrelease.
✓TheycontainWater-solubledrugs.
✓Thatdisintegratesinthestomachandgastricfluidafter
swallowing.
✓Drugcontentisabsorbedinthegastrointestinaltractand
distributedintothewholebody.
✓Ex.Paracetamol,Diazepam,etc.

10. Classification of Tablets
1.Tablets Ingested Orally
II.Multiplecompressedtablets
✓Preparedtoseparateincompatibleingredient'sortoproducerepeat-actionor
prolonged-actionproducts.
✓Topreventincompatibility,formulationingredientsarecompressedintoacore
tablet,followedbyincompatiblesubstancesandnecessaryexcipients,toensure
compatibility.
✓Specialtablet-makingmachinesarerequired.
✓Ex.MetoprololSuccinate(Extended-Release),Janumet XR
(Sitagliptin/Metformin)
Enablestheprolongedreleaseofmetforminandprovidesimmediate-release
sitagliptintoeffectivelymanagebloodsugarlevels.
✓MCTsoffertheadvantageofprovidingacontrolledreleaseprofile,whichcan
enhancetherapeuticeffectivenessandimprovepatientcompliance.

11. Classification of Tablets
1.Tablets Ingested Orally
III.Multilayered tablet:
✓Thesetabletsconsistoftwoormorelayerofmaterialscompressed
successfullyinthesametablet.
✓Thecolorofeachlayermaybethesameordifferent.
✓Atablethavinglayersofdifferentcolorsisknownasamulticolortablet.
✓Thesetabletsarepreparedtoseparateincompatibleingredientsphysically.
✓Ex. Zolpidem CR, Janumet XR (Sitagliptin/Metformin)
IV.Sustained release tablet:
✓These tablets are designed to provide medicaments for longer periods of
time in a controlled manner.
✓After oral administration, they provide an initial amount of drug to cause
rapid onset of actionand additional amt. of the drug to maintain the
prolonged effect of the medicament.
✓Thus maintaining a constant blood concentration.

12. Classification of Tablets
1.Tablets Ingested Orally
V.Enteric-coated tablets
✓These tablets are conventionally compressed tablets coated with enteric
coating materialsthat resist the dissolution in the stomach but dissolve in
the intestine.
✓The solubility of enteric coating materials is pH-dependent.
✓It has delayed release property.
✓Ex. Aspirin(to reduce stomach irritation), Omeprazole (Proton pump inhibitors)
VI.Sugar-coated tablets:
✓The compressed tablets having a sugar coatingare called sugar-coated tablets.
✓Sugar coating is done to mask the bitter and unpleasant order and the taste of
the medicament.
✓The sugar coating makes the tablets, elegant and safeguards the drug from
the atmospheric effect.
✓Ex. Ibuprofen, Vitamin Supplements, Antibiotics

13. Classification of Tablets
1.Tablets Ingested Orally
VII.Film-coated tablet:
✓Thecompressedtablethavingafilmcoatingofsomepolymersubstance,
suchashydroxypropylcellulose,hydroxypropylmethylcellulose,and
ethylcellulose.
✓Thefilmcoatingprotectsthemedicamentfromtheatmosphericeffect.
✓Thefilm-coatingtabletsaregenerallytasteless,havelittleincreaseinthe
tabletweight,andhavelesselegancethansugar-coatedtablets.
✓Ex.Acetaminophen,Metformin,Amlodipine,Atorvastatin
VIII.Chewable tablets
✓Chewabletabletsmaybedefinedastabletsthataredesignedtobeprocessed
bychewingtofacilitatethereleaseofactivegradients.
✓Chewabletabletscanbechewedbeforeswallowingandbrokeninto
smallerpieces.
✓Ex.Antacids,Children'sVitamins,VitaminC,Probiotics

14. Classification of Tablets
2.Tablets used in the Oral Cavity
I.Buccal tablets:
✓Thesetabletsaretobeplacedinthebuccalpouch(cheek)orbetweenthe
gumsandlipswheretheydissolveordisintegrateslowlyandareabsorbed
directlywithoutpassingintotheelementarycanals.
✓Ex-NitroglycerinBuccalTablets,Fentanyl
II.Sublingual tablets:
✓Thesetabletsaretobeplacedunderthetonguewheretheydissolveor
disintegratequickly,andareabsorbeddirectlywithoutpassingintoGIT.
✓Thismethodalsoavoidsfirst-passmetabolismbytheliver.
✓Ex-Glyceryltrinitrate.

15. Classification of Tablets
2.TabletsusedintheOralCavity
III.Lozengetablets&Troches:
✓Thesetabletsaredesignedtoexertalocaleffectinthemouthorthroat.
✓Commonlyusedtotreatsorethroatortocontrolcoughingincommoncold.
✓Theymaycontainlocalanesthetics,antiseptics,antibacterialagents,astringent,
andantitussives.
✓Theseareformulatedwithhigh-pressurecompressionormoulding,typically
containingsweeteningagents,flavoringagents,andcoolingsubstancesalongside
themedication.
✓Ex-Vicks,Strepsils,coflets,etc.
IV.Dentalcones:endodonticconesorrootcanalcones
✓Thesearerelativelyminorcompressedtabletsmeanttobeplacedintheempty
socketaftertoothextraction.
✓Theypreventthemultiplicationofbacteriainthesocketfollowingsuch
extractionbyusingslow-releaseantibacterialcompoundsortoreducebleeding
bycontainingtheastringents.
✓Ex-CalciumHydroxideCones-Usedfortheirantimicrobialpropertiesandto
inducehardtissueformation,oftenusedfortemporaryfilling

16. Classification of Tablets
3.Tablets used to Prepare Solutions
1.Effervescent tablets:
✓These tablets, when added to water, produce effervescence. So they dissolve rapidly in water
due to chemical reactions, which take place between alkali bicarbonate and citric acid, or
tartaric acid, or a combination of both.
✓These tablets are to be protected from atmospheric moisture during storage.
✓So these tablets should be stored in a whale, closed airtight container.
2.Dispensing tablets:
✓This type of tablet are intended to be added to the given volume of water toproduce solution
of a given concentration.
✓These tablets contain excipients which gate dissolves quickly to form clear.
✓These tablets are highly toxic if taken orally by mistake. So great care must be taken in the
packaging and labeling of such tablets in order to prevent their misuse.

17. Classification of Tablets
3.Tablets used to Prepare Solutions
III.Hypodermic tablets:
✓Thesearecompressedtablet,whicharecomposedofoneormoredrugwithreadilywatersoluble
ingredient.
✓Thesetabletsaredissolvedinsterilewaterorwaterforinjectionandadministeredbyparental
route.
✓Sospecialprecautionsareneededtobetakenduringtheirpreparation.
✓Thesetablets,however,arenotpreferredastherearechancesthatthesolutionpreparedfrom
hypodermictabletsmaybenon-sterile.
✓Ex.Morphinesulphate
IV.Tablet Triturate:
These are small tablets usually cylindrical mouldedor compressed and contain potent predicament
with diluent.
On a small scale tablet, triturate are prepared by using hand operated tablet triturates mouldsfor
bulk production atomic tablet triturate at machines used.

18. Classification of Tablets
4.Tablets administered by other routes
I.Implants:
✓Thesetabletsareplacedundertheorinsertedusingminorsurgical
operations.
✓Thesetabletshaveslowabsorptionandprovidecontinuousreleaseofdrugsfor
monthsorayear
✓Thesemaybemadebyheavycompression,orbyfusion.
✓Mustbesterileandshouldbeplacedindividuallyinsterileconditions.
✓usedforadministrationofhormones,suchastestosteroneand
deoxycorticosterone.Etc
✓Ex-Nexplanon(EtonogestrelImplant),Zoladex(GoserelinAcetateImplant)
II.Vaginal tablets (Inserts):
✓These tablets are made to dissolve slowly in the vaginal cavity.
✓The tablets are ovoid or pear-shaped, bullet-shaped for ease of insertion and to
facilitate retention in the vagina.
✓Used to release steroid antibacterial agents, antiseptics, or astringent to treat
vaginal infections.
✓The tablets are often buffered to promote a pH favorable to the action of a
specified antiseptic agent.

19. Excipients or Formulation of Tablets
ExcipientsSubstances other than the active ingredients are commonly referred to as excipients
or additives.
Tablet = API + Excipents
The International Pharmaceutical Excipients Council (IPEC) defines excipientsas any
substances other than the active drug or prodruginducedin the manufacturing processes or is
continued in finished pharmaceutical dosage forms.
Ideal Characteristics of Excipients
1.Non-toxicand regulatory-acceptable substances.
2.Commercially available in acceptable grades in all manufacturing countries.
3.Low cost.
4.Physiologically inert.
5.Physical and chemically stable by themselves and with drug(s)and other tablet components.
6.Free from microbes.
7.Compatible with color without off-color appearance.
8.Approved as food additives if the drug product is also classified as food.
9.Does not affect the bioavailability of the added drug(s).

20. Group I
Diluents
Granulating
agents
Binders
Disintegrates
Glidants
Lubricants
Anti-adhesive
agents
Group II
Sweetening
agent
Coloringagent
Flavors agent
Group III
Polymers
Excipients or Formulation of Tablets

21. 1.Fillers/Diluents
Fillers (or diluents) are inert substances added to increase the bulk to make the tablet of the
required size for compression.
Properties of an Ideal Diluent
✓Ideally, diluents should be chemically inert, non-hygroscopic, and hydrophilic.
✓An acceptable taste is important for oral formulations,
✓Costis always a significant factor in excipient selection.
✓Examples: Diluents like mannitol, lactose, sorbitol, and sucrose
✓Microcrystalline cellulose is usually used as an excipient in direct compression formula.
✓Hydroxy Propyl Methyl Cellulose (HPMC) is used to prolong the release of active ingredients
from the tablet and also as a film former in tablet coating.
✓An inert substance is frequently added to increase the bulk of a tablet for processing and handling.
Excipients or Formulation of Tablets

22. 2.Granulating agents:
✓These are used to convert fine powder into granules, a granulating agent provides proper
moisture to convert fine powder into damp mass, Which after passing through a sieve of a
suitable number forms granules.
✓The various granulating agents used are water, alcohol, mucilage of starch, mucilage of
acacia, mucilage, tragacanth, gelatin solution, isopropyl alcohol, acetone, etc.
3.Binding agents:
✓These are used in granulation to provide proper strength to the granules to keep the tablet
intact after compression.
✓Binding agents are used along with granulating agents.
✓Binding agents used are gum acacia powder, gum tragacanth, gelatin sucrose,
methylcellulose, starch paste, etc.
✓The selection of the proper binding agent and its concentration depends on the type of
tablets for which it is used.
✓In lozenges tablets and implants the proportion of binding agents has to be very high.
✓ Whereas in another case where the tablets have to disintegrate quickly a binding agent with
less binding properties and lower concentration is used.
Excipients or Formulation of Tablets

23. 4.Disintegrating agents:
✓The substances that are added in the tablet formulation to ensure disintegration of the tablets into
smaller particles when swallowed, are called as disintegrating agents.
✓These are added into the formulation of oral tablets or sublingual tablets.
✓When the medicament is insoluble in water disintegrating agent is needed.
✓Disintegrating agents act in three ways.
i.By swelling: Decent decreasing agent gate swelled when it came in contact with water or
moisture.
For example, potato starch, maize starch, wheat starch methylcellulose or bentonite. Potato
starch is Superior to other starches, but maize starch is commonly used because it is very
cheap.
ii.By producing effervescence: They produce information when they come in contact with
moisture.
For example, sodium bicarbonate, citric acid, and tartric acid.
iii.They melt at a body temperature, for example, cocabutter.
✓The disintegrating agent is divided into two parts. 1 part is mixed along with other excipients
before the formulation of granules. The other part is mixed with dry granules before
compression.
Excipients or Formulation of Tablets

24. 5.Superdisintegrants:
✓Newer disintegrants, including modified starches, modified cellulose, and crosslinked
polyvinyls, are effective at lower levels.
✓Mechanisms include water wicking, swelling, deformation resistance, repulsion, and
heat of wetting.
✓Examples include sodium starch glycollate, which can swell up to 12 times in less than
30 seconds.
✓Crospovidone, a completely insoluble polymer, exhibits high capillary activity and
hydration capacity but does not gel.
✓Croscarmellose sodium, a cross-linked polymer, is also insoluble in water but rapidly
swells to 4-8 times its original volume.
Excipients or Formulation of Tablets

25. 6.Lubricants:
✓Lubricants prevent the adhesion of the tablet material to the surface of dies and punches,
reduce inter-particle friction, facilitate an easy ejection of tablets from the die cavity, and
improve the flow rate of tablet granules.
✓Lubricant properties include reducing friction between particles and machine surfaces,
compatibility with API and other excipients, and concentration.
✓Selection criteria include type of dosage form, API's sensitivity to hydrophobic or hydrophilic
environments, and manufacturing process.
✓Lubricants' impact on tablet properties includeshardness,disintegrationtime,anddissolution
rate.
✓Examples include magnesium stearate, stearic acid, polyethylene glycol (PEG), sodium stearyl
fumarate, and talc.
✓Applications include pharmaceutical tablets, capsules, and powder blends to improve
manufacturing, flow, and handling characteristics.
Excipients or Formulation of Tablets

26. 6.Glidants:
✓They improved the flow properties of granules from the hopper to die of the tablet
machine.
✓They are always added in the dry state just before compression.
✓The most commonly used glidants are colloidal silicon dioxide and asbestos-free talc.
✓Talc, used in concentrations below 1%, serves as a dual-purpose lubricant/glidant, and
anti-adherents are added to formulations prone to sticking to the die surface.
7.Anti-adhesive agents:
✓These prevent the sticking of the tablet surface to die and punches during
compression.
✓Water-insoluble lubricants like magnesium stearate, talc, liquid paraffin and starch can
used as anti-adherents.
Excipients or Formulation of Tablets

27. 8.Colouring agents:
✓Colors of approved, certified FD and C dyes are used.
✓The colors are used to improve the elegance of the tablet.
✓Aid in product identification and Enhance patient compliance.
✓The colors are added to the solution of granulating agents or mixed with ingredients before
granulation.
✓For example, FD&CRedNo.40,FD&CYellowNo.5.D&CRedNo.33,D&CYellowNo.10.
✓Their selection depends on factors like solubility, stability, compatibility, and regulatory approval.
9.Flavouring agents:
✓Flavours are induced in lozenges, effervescent tablets and chewable tablets.
✓Flavours are volatile oils, and hence they are added into the granules just before the compression of
tablets.
✓ The flavoring agent is dissolved in organic solvent and the solution is sprayed on the granules.
✓Ex. Mint, Orange, Menthol, Ginger, etc
Excipients or Formulation of Tablets

28. 10.Sweetening agents:
✓Sweetening agents are used to improve the taste of tablets
✓These are used in lozenges and chewable tablets.
✓Increase the acceptability of tablets.
✓Sucrose, Lactose, and Manitol are some of the commonly used wedding agents.
11.Adsorbing agents:
✓The substances can use to adsorb volatile oil, liquid extract and tinctures. etc, Which are
included in the formulation of tablets.
✓Enhancing the stability, effectiveness, or manufacturability of the dosage form.
✓Commonly used adsorbent are Silica Gel,magnesium carbonate kaolin and starch.
✓Their selection depends on the specific requirements of the formulation and the nature of
the API.
Excipients or Formulation of Tablets

29. 12.Polymer agents:
✓Polymer are versatile excipients used in pharmaceutical formulations to provide structural support,
control drug release, enhance stability, and improve the overall performance of the dosage form.
✓They can be natural, synthetic, or semi-synthetic.
✓Hydroxypropyl Methylcellulose (HPMC) is a versatile binder, film-former, and controlled-release
agent, forming a gel upon hydration. Polyvinylpyrrolidone (PVP), Ethylcellulose,
✓Polymer agents are crucial in pharmaceutical formulations for their ability to modify the physical
and chemical properties of the dosage form, ensuring optimal performance, stability, and patient
compliance.
Excipients or Formulation of Tablets

30. GRANULATION
✓Granulation is the act or process of forming or crystallizing into grains. Granules
typically have a size range between 0.2 and 4.0 mm, depending on their subsequent use.
✓Granulation may be defined as a size enlargement process that converts small particles
into physically stronger and larger agglomerates.
✓ The granulation process will improve flow and compression characteristics, reduce
segregation, improve content uniformity, and eliminate excessive amounts of fine particles.
Following are the benefits of granulation:
✓To enhance flow properties.
✓To produce a uniform mixture
✓To improve compaction characteristics.
✓To avoid powder segregation.

31. Granulation
method
Wet Granulation
Fluid bed dryer
Extrusion/
spheronisation
Fluid bed Coater
Spray dryer
Dry Granulation
Slugging
Direct compression
Roller
compactor
➢Various granulation
techniques
1.Wet granulation method.
2.Dry granulation method.
3.Direct compression method
4.Hot melt granulation Process
5.Top spray granulation method.
6.Melt granulation method.
7.IGL line

32. 1.Wet Granulation:
In this method, the powdered drug and excipients are mixed
together and then a binding liquid is added to form a wet
mass. The wet mass is then dried and milled to produce
granules with improved flow and compaction properties.
Steps Involved in Wet Granulation
The liquid is added while mixing the previously dried materials. To
achieve a narrow particle size distribution, the moist mass is kneaded
into the wet mass. Then the granules are wet-sieved, dried, and sieved
again. The amount of liquid is critical because overwetting may
result in uncontrollable agglomerate growth.
Weighing
Dry Mixing
Wet Mixing/
Wet
Granulation
Wet Milling
Drying
Sizing/Milling
Lubrication/
Mixing
Compression

33. 1.Wet Granulation:
The blending and granulation techniques
involve an extensive use of high-shear
mixers in pharmaceutical industries.
This type of instrumentation utilizes a
high-speed (50-150 rpm)rotating
impellerto set the particles into
movement.
It also utilizes achopper (1500 -4000
rpm) to break down the large lumps into
smaller fragments. This increases the
uniform distribution of binder in the
blend.
Uses in three phases of the wet
granulation
i) Dry powder mixing,
ii) Liquid binder addition, and
iii) Wet massing.

34. Wet Granulation:
Advantages
➢Short processing time.
➢Less amount of liquid binders required.
➢Good flow properties.
➢Better uniformity and good PSD.
➢Highly cohesive materials can be granulated.
Disadvantages
➢Fragile particles may undergo mechanical degradation.
➢Large-size lumps may form as a result of over-wetting of granules.
➢More steps required more labours and time.
Weighing
Dry Mixing
Wet Mixing/
Wet
Granulation
Wet Milling
Drying
Sizing/Milling
Lubrication/
Mixing
Compression

35. ➢Fluidisation is the operation by which fine solids are transformed into a fluid-like state through
contact with a gas.
➢Fluid bed granulation is a process of producing granules in a single piece of equipment utilizing the
spraying of a binder solution against a fluidized powder bed.
➢In this system, heated air is directed across the material to be processed.
➢Afterwards, the heated air leaves through the voids of the material. This technique is known to produce
fine, free-flowing, and homogenous material.
➢Air Handling Unit (AHU), product container, air distributor, spray nozzle, disengagement area, process
filters, exhaust blower or fan, control system, and solution delivery system are the components in a
fluidized bed system.
Advantages
➢Improves quality by reducing dust formation during processing.
➢Product loss is reduced.
➢Ensures the safety of the worker.
Disadvantages
➢Cleaning of fluid bed is a labor-intensive and time-consuming process.
➢Reproducibility in manufactured products is not possible.
Fluid bed dryer

36. Fluid bed dryer

37. Spray Drying Granulation:
It is a widely used technique for producing dry granules from a liquid solution, suspension, or
slurry. This method is trendy in the pharmaceutical, food, and chemical industries for creating free-
flowing, uniform granules.
The three fundamental steps involved in spray drying process are:
I.Fine droplets are produced by atomizing the liquid feed.
II.These spray droplets are mixed with a heated gas stream, resulting in the evaporation of liquid
leaving behind the dried solid particles.
III.The dried powder is separated from the gas stream
Advantages
I.Rapid and continuous process.
II.Avoids labor-intensive drying and granulation steps,
thus, making it more economical.
III.OTC products are usually produced.
IV.Suitable for thermolabile substances.

38. Extrusion and Spheronisation:
➢Extrusion and spheronization is a pelletisation technique that was developed in the early 1960s.
➢This process is commonly used in the pharmaceutical industry to make uniform-size spheroids.
➢It is especially making dense granules for controlled solid oral doses form with a minimum amount
of excipient.
Principle: Wet Mass material is forced through different mesh size screens which Produce road-shaped
particles of uniform diameter.
➢This process is highly valued for its ability to produce pellets with high density, narrow size
distribution, and excellent flow properties.
➢This produces a variety of shapes of spheroids like radial, axial, cylindrical, and rod-shaped.

39. Extrusion and Spheronisation:
1.Extrusion: The extrusion process involves converting a wet mass or paste into cylindrical
extrudates (rod-shaped particles).
1.Wet Granulation: a powder mixture containing the API and excipients is granulated with a
binding liquid to form a wet mass.
2.Extrusion: The wet mass is then forced through a die with circular holes, producing
cylindrical extrudates with a consistent diameter. The extruder can be of various types,
including screw extruders, piston extruders, or basket extruders.
2.Spheronisation: This process transforms the cylindrical extrudates into spherical pellets/Spheres.
3.Spheronisation: The cylindrical extrudates are placed on a rotating spheronisation plate. The
plate, usually grooved or textured, spins rapidly, causing the extrudates to collide with each other
and the plate’s surface. This friction and impact round off the edges, forming spherical
pellets.
4.Drying: The spherical pellets are then dried to achieve the desired hardness and stability.

40. 2.Dry Granulation:
➢ The dry granulation process is used to form granules without using
liquid solution, because the product granulated may be sensitive to
moisture and heat.
➢Dry granulation is a powder agglomeration process used in the
pharmaceutical industry to improve the flowability of powders by
increasing the particle size.
➢This method is also called as double compression method.
➢Forming granules without moisture required compacting and
densifying powders.
➢In this process, the primary powder particles are aggregated under
high pressure.
➢The operation is achieved by using a roller compactor, which can
have different configurations and equipment designs.
Dry Granulation
Slugging
Direct compression
Roller compactor

41. ➢Slugging: Granulation by slugging is the process of compressing dry powder of tablet
formulation with tablet press having a die cavity (large enough in diameter to fill quickly). The
accuracy or condition of slug is not too important.
➢Only sufficient pressure to compact the powder into uniform slugs should be used.
➢Once slugs are produced they are reduced to appropriate granule size for final compression by screening
and milling.
Steps in slugging
1) Milling of drugs and excipients,
2) Mixing of milled powders,
3) Compression into large, hard tablets to make slug,
4) Screening of slugs,
5) Mixing with lubricant and disintegrating agent, and
6) Tablet compression
Factors determining a material's slug ability:
➢Compressibility or cohesiveness of the matter,
➢Compression ratio of powder,
➢Density of the powder,
➢Machine type,
➢Punch and die size,
➢Slug thickness,
➢Speed of compression, and
➢Pressure used to produce slug.

42. Roller compaction and Slugging

43. Roll compactor
➢ Dry granulation is commonly used in many industries to alter the particle size and
bulk density of materials.
➢The theory of roller compactor technology takes a light small powder from the
feed hopper and introduces it to the feeding system (feed screw).
➢The feed screw precisely meters the material into a set of counter-rotating rolls
that compress the ribbon into solid long flakes.
➢The flakes are then gently milled to the required particle size.
➢This multistep process ensures minimum amount of fines are generated in this
process.
➢Replacing traditional granulation methods, roller compaction technology has
several advantages by using the dry process, including speed of processing, lack
of moisture introductions, precise control of the particle size, faster process
time, considerable less capital investment and considerable savings in
consumption and floor space.

44. Roll compactor
Make-Alexanderwork
Model- WP200

45. Direct compression
➢Direct compression is the most straightforward manufacturing option, with the fewest
manufacturing steps, making it easiest to control and least expensive.
➢In DC blending the API with excipients and compressing the finished tablets.

46. Advantages
➢It utilises less equipment and space.
➢It does not require binder solution and heavy mixing equipment.
➢The costly and time -consuming drying step required for wet granulation is also avoided.
➢It is suitable for moisture- and heat-sensitive materials.
➢Tablets with improved disintegration are produced as powder particles are not bonded
together by a binder.
➢Solubility of the drug is also improved.
Disadvantages
➢It requires a specialised heavy duty tablet press to form the slug.
➢It does not permit uniform colour distribution.
➢It creates more dust than wet granulation, thus, increasing the potential contamination.

47. COMPRESSION
➢Tablet compression is a process used in the pharmaceutical industry to form tablets from powdered
material.
➢Essential for ensuring consistent dosage and stability of pharmaceutical products.
➢The distance between the upper and lower punches determines the thickness and hardness of the tablet.
➢The proper balance of thickness and hardness determines the optimum roll distance for any specific product.
➢Widely used in the production of various types of tablets, including medicinal, nutritional, and cosmetic.
➢The various types of compression machines
i.Single punch tablet machine Which may be hand-operated or electrically operated
ii.Multi-punch tablet machine
iii.Rotary tablet machine.
iv.Dry quota tablet machine.
➢In all these tablet machines, compression is achieved by filling the required quantity of granules
into the dies and then compressing them in between the lower punch and the upper punch. The
singlepunchmachineisusedforsmall-scalemanufacturing, whereas theothermachinesareusedfor
large-scalemanufacturing,rotary machines having about 70 sets of dies produce about 1200 tablets
in one minute.

48. COMPRESSION
❑Single punch tablet machine
➢The single-punch tablet machine has the following major part.
i.Hopper shoe: To supply the granules into the dye and to remove the tablet
after the compression.
ii.Lower punch
iii.Upper punch
iv.Capacity regulator: To adjust the position of the lower punch to
accommodate the required constituencies by the die.
v.Ejection regulator: To adjust the position of the lower punch, so that its
highest position is at par with the surface of the dye.
vi.Die: It allows the lower punch and the upper punch to come closer together
to comprise the granules.
vii.Driving Wheel: It helps in the moment of the lower punch, the upper
punch and the hopper shoe. And also check their movement.

49. ❑Single punch tablet machine
1.Powder is kept in a hopper connected to a hopper shoe at the die table.
2.The hopper shoe moves rotationally or translationally over the die.
3.The powder is fed into the die via gravitational powder flow.
4.The lower punch controls the quantity of powder.
5.The upper punch compresses the powder while the hopper shoe is near the die.
6.The lower punch remains stationary during compression, while the upper punch applies pressure.
7.After ejection, the hopper shoe moves back to the die for the next tablet.
8.A single punch press can produce up to 200 tablets per minute.
COMPRESSION

50. ❑Multi-punch tablet machine (Multi-Station)
➢Multi-station presses are also termed rotary tablet machines.
➢The head portions holding the upper and lower punches are called the upper and lower
turrets, respectively, and the portion holding the dies is the die table.
➢The fundamental principle revolves around the simultaneous action of multiple
compression stations arranged in a rotating turret. This setup allows for continuous
production, making it highly efficient for large-scale manufacturing.
➢As the head rotates, the punches are guided up and down by fixed cam tracks, which control
the filling, compression, and ejection sequence.
COMPRESSION

51. ❑Multi-punch tablet machine (Multi-Station)
COMPRESSION

52. Components of a Multi-Station Press
1.Hopper: The granules or powder mixture containing API and excipients are
poured into the hopper before compression.
2.Die Cavity: Here the powder granules are compressed into tablets. The die is
responsible for determining the diameter, size, and thickness of the tablet.
3.Feed Paddle: This rotates at a fast speed to force the feed or granules into
the dies.
4.Punches: These include the upper and lower punches which move within
the die bore to compress granules into tablets.
5.Lower Cam Track: This allows accurate adjustment by permitting the
overfilling of die bore by guiding the lower punch during the filling stage.
6.Cam Truck: This guides the position and movement of the punches.
COMPRESSION

53. ❑Multi-punch tablet machine (Multi-Station)
COMPRESSION

54. Components of a Multi-Station Press
7.Department of Fill/Capacity Control: This ensures that a suitable quantity of
granules fills the die before the compression process by adjusting the lower punch
track during the latter part of the fill stage.
8.Precompression Rollers: These provide an initial compression force to the
granules for removing the excess air entrapped in the die.
9.Main Compression: This provides the final compression force required for the
formation of tablets.
10.Ejection Cam: This is utilised to facilitate the ejection of tablet from the die cavity
after compression.
11.Take-off Blade: This is fitted opposite to the feeder housing and deflects the tablet
down the discharge chute.
12.Discharge Chute: After being deflected by the take-off blade , the tablet passes
through the discharge chute for collection.
COMPRESSION

55. ❑Multi-punch tablet machine (Multi-Station)
Advantages
➢Enhanced Drug Stability: Separates incompatible ingredients to prevent degradation.
➢Controlled Release Profiles: Enables sustained, delayed, or multi-phase release.
➢Combination Products: Incorporates multiple active ingredients in one tablet.
➢Improved Patient Compliance: Reduces the number of pills needed.
➢Aesthetic & Functional Differentiation: Allows distinct layers for identification and
coatings.
➢Customization & Flexibility: Tailors each layer for optimal formulation.
➢Minimized Cross-Contamination: Isolates manufacturing processes for safety.
➢Optimized Efficiency: Streamlines complex tablet production in a single process.
COMPRESSION

56. Tablet Tooling
➢Tablet tooling refers to designing and manufacturing the punches and dies used in the tablet
compression process.
➢The punches and dies define tablets’ size, shape, and markings.
➢Proper tablet tooling is critical to producing high-quality tablets that meet the desired
specifications for pharmaceutical use.
➢Tablets are Manufactured in circular, oval, or oblong shapes, Other shapes include triangular and
diamond.
➢When viewed sideways: flat or convex, with or without beveled edges.
➢Break marks, symbols, or other markings may be present. Break marks or lines ensure controlled
breakage for reproducible doses, and embossed (raised on tablet surface) and debossed (indented into
tablet).

57. Tablet Tooling
Key Aspects of Tablet Tooling
1.Punches and Dies:
i.Punches: The upper and lower components that compress the powder into tablets.
Punches can have different head shapes (round, oval, etc.), embossing, and engraving to
define the tablet's appearance.
ii.Dies: The cavity where the powder is compressed by the punches to form the tablet. The
die defines the tablet's size and shape.
2.Tooling Standards:
i.B-Tooling: A standard for smaller tablet sizes, commonly used in high-volume
production.
ii.D-Tooling: A standard for larger tablets, offering more volume for compression,
typically used for large-dose medications or multi-layer tablets.
iii.Other Standards: Some manufacturers use special standards like BB or DB tooling for
specific needs.

58. Tablet Tooling
Lower Punch

59. Tablet Tooling
Key Aspects of Tablet Tooling
3.Tooling Configuration:
1.Single Station Tooling: Used in smaller-scale or laboratory tablet presses where only one tablet
is compressed at a time.
2.Rotary Tooling: In large-scale production, multiple punches and dies are arranged on a
rotating turret, allowing for high-speed tablet production.
4.Tablet Shape and Design:
Tooling allows for customization of the tablet's shape (round, oval, square, etc.), size, and markings
(logos, scoring lines), which are essential for product differentiation and ease of use for patients.

60. Tablet Tooling
Key Aspects of Tablet Tooling

61. Compression and Processing Problems
CappingLaminationPicking Sticking
ChippingMottling
Weight
Variation
Hardness
Variation
FriabilityCracking Binding
Double
Impression
Over-
Compression
Common defects in tablets during compression & Remedies

62. Compression and Processing Problems
Causes:
➢Excessive air entrapment during compression
due to excessive fines in granules
➢Inadequate binder or improper granulation.
➢High compression force.
➢Granules are improperly dried.
➢Worn or damaged tooling (punches/dies).
➢Lower punch remains below the die face during
ejection.
➢Turret speed is high.
Remedies:
➢Optimize granulation to reduce air
entrapment.
➢Adjust compression force to the appropriate
level.
➢Ensure proper binder concentration.
➢Regularly inspect and maintain tooling.
➢Compression is carried out at room temperature
➢Dies are properly finished
➢Flat punches are used.
➢Turret speed is reduced.
Common defects in tablets during compression & Remedies
1.Capping and Lamination:
1.Capping: The top or bottom layer of the tablet separates or breaks off.
2.Lamination: The tablet separates into two or more distinct horizontal layers.

63. 2.Picking and Sticking:
In picking the material is removed or picked up by the upper punch and the surface of the
tablet.
In case of sticking, the material sticks to the wall of the die.
Causes:
➢Excessive moisture in the formulation.
➢Inadequate or improper lubricant.
➢Too much binder or sticky excipients/ Granular material is hygroscopic.
➢Rough or worn tooling surfaces.
➢Pressure is low.
Remedies:
➢Dry the granules properly
➢Optimize lubricant concentration and use hydrophobic lubricants if necessary.
➢Use tooling with smoother surfaces or apply anti-sticking coatings
➢Pressure is increased.
Compression and Processing Problems

64. 3.Mottling:
Uneven color distribution on the tablet surface leads to a mottled or spotted appearance.
This defect is commonly observed in colored tablets due to migration of dye.
Causes:
➢Uneven distribution of colorants or dyes.
➢Migration of dye during drying.
➢Incompatibility between excipients and colorants.
➢A coloured drug used along with colour-less or white-coloured excipients.
Remedies:
➢Ensure uniform mixing of colorants and excipients.
➢Optimize drying conditions to prevent dye migration.
➢Consider using different types of colorants (e.g., lake pigments).
➢Use appropriate colourants.
Compression and Processing Problems

65. Causes:
➢Inadequate tablet hardness due to low
compression force.
➢Poor granulation quality (e.g., improper
particle size distribution).
➢Fragile tablet design (sharp edges or thin
tablets).
➢Sticking on punch faces.
➢Too dry granules.
➢Too much binding causes chipping at bottom.
➢Groove of die worn at compression point.
➢Edge of punch face turned inside/inward.
➢Concavity too deep to compress properly.
Remedies:
➢Increase compression force.
➢Improve granulation with better binder use or
optimization of particle size.
➢Modify tablet design to reduce fragility.
➢Add hygroscopic substances.
➢Polish to open end, reverse or replace the die.
➢Polish the die to make it cylindrical.
➢Polish the punch edges.
➢Reduce concavity of punch faces.
➢Use flat punches.
Compression and Processing Problems
4.Chipping:
Chipping is defined as the breaking of tablet edges into Small pieces, typically during
handling or packaging.

66. Causes:
➢Poor flow properties of the powder or
granules.(from hopper to die)
➢Incorrect machine settings (e.g., feeder speed,
turret speed).
➢Inconsistent granule size or density.
➢Due to the presence of under dried granules
➢Too large granules, large proportion of fines
➢No proper mixing of lubricants.
Remedies:
➢Improve powder flow by optimizing
granulation or adding flow agents.
➢Adjust machine settings for consistent feed and
compression.
➢Ensure uniform granule size and density.
Compression and Processing Problems
5.Weight variation:
During the compression of granules in a tablet machine tablets do not have
consistent weights, leading to variability in dosage.

67. Causes:
➢Variation in compression force during the process.
➢Inconsistent granulation or moisture content.
➢Worn tooling causing uneven compression.
Remedies:
➢Monitor and standardize compression force.
➢Ensure consistent moisture content and granulation quality.
➢Regularly inspect and replace worn tooling.
Compression and Processing Problems
6.Hardness:
During the compression of granules, tablets exhibit inconsistent hardness, affecting
their dissolution profile and mechanical strength.
Hardness variation is a problem having the same causes as weight variation