In the changing scenario of pharmacy practice in India, for successful practice of Hospital Pharmacy, the students are required to learn various skills like drug distribution, drug dispensing, manufacturing of parenteral preparations, drug information, patient counselling, and therapeutic drug monitoring for improved patient care

1. DOCTOR OF PHARMACY
IV YEAR
Tablets
CHAPTER-6 c
MANUFACTURING OF PHARMACEUTICAAL P
REPARATIONS
Dr.V.Chanukya Pharm D

2. DEFINITION
• 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
• They may vary in size, shape, weight, hardness, thickness, disintegration and dissolution
characteristics, and in other aspects.
• They may be classyfied, according to the method of manufacture, as compressed tablets or
molded tablets.

3. Disadvantages
Production aspect
• Large scale production at lowest cost
• Easiest and cheapest to package and ship
• High stability
User aspect (doctor, pharmacist, patient)
• Easy to handling
• Lightest and most compact
• Greatest dose precision & least content
variability
• Some drugs resist compression into dense
compacts
• Drugs with poor wetting, slow dissolution,
intermediate to large dosages may be difficult or
impossible to formulate and manufacture as a
tablet that provide adequate or full drug
bioavailability
• Bitter taste drugs, drugs with an objectionable
odor, or sensitive to oxygen or moisture may
require encapsulation or entrapment prior to
compression or the tablets may require coating
Advantages

4. Different types of Tablets
Tablets ingested orally:
1. Uncoated tablet
2. Multiple compressed tablet
3. Repeat action tablet
4. Delayed release tablet, e.g. Enteric coated
5. Sugar coated tablet, e.g. Multivitamin tablet
6. Film coated tablet, e.g. Metronidazole tablet
7. Chewable tablet, e.g. Antacid tablet
Tablets used in oral cavity:
1. Buccal tablet, e.g. Vitamin-c tablet
2. Sublingual tablet, e.g. Vicks Menthol
tablet
3. Troches or lozenges
4. Dental cone

5. Different types of Tablets
Tablets administered by other route:
1. Implantation tablet
2. Vaginal tablet, e.g. Clotrimazole tablet
Tablets used to prepare solution:
1. Effervescent tablet, e.g. Dispirin tablet
2. Dispensing tablet, e.g. Enzyme tablet
3. Hypodermic tablet
4. Tablet triturates e.g. Enzyme tablet

6. Uncoated Tablets
• Uncoated tablets include single-layer tablets resulting from a single
compression of particles
• Multi-layer tablets consisting of concentric or parallel layers obtained by
successive compression of particles of different composition.
• The excipients used are not specifically intended to modify the release of the
active substance in the digestive fluids.

7. Coated Tablets
• Coated tablets are tablets covered with one or more layers of mixtures of various substances
such as natural or synthetic resins, gums, gelatin, inactive and insoluble fillers, sugars,
plasticisers, polyols, waxes, colouring matter authorised by the competent authority and
sometimes flavouring substances and active substances.
• The substances used as coatings are usually applied as a solution or suspension in
conditions in which evaporation of the vehicle occurs.
• When the coating is a very thin polymeric coating, the tablets are known as film-coated
tablets.
• Coated tablets have a smooth surface, which is often coloured and may be polished; a
broken section, when examined under a lens, shows a core surrounded by one or more
continuous layers with a different texture.

8. Gastro-resistant Tablets
• Gastro-resistant tablets are delayed-release tablets that are intended to resist the gastric
fluid and to release their active substance(s) in the intestinal fluid.
• Usually they are prepared from granules or particles already covered with a gastro-
resistant coating or in certain cases by covering tablets with a gastro-resistant coating
(enteric-coated tablets).

9. Modified-Release Tablets
• Modified-release tablets are coated or uncoated tablets that contain special excipients or are
prepared by special procedures, or both, designed to modify the rate, the place or the time at
which the active substance(s) are released.
• Modified-release tablets include prolonged-release tablets, delayed-release tablets and
pulsatile-release tablets.

10. Effervescent Tablets
• Effervescent tablets are uncoated tablets generally containing acid substances and
carbonates or hydrogen carbonates, which react rapidly in the presence of water to
release carbon dioxide.
• They are intended to be dissolved or dispersed in water before administration.

11. Soluble Tablets
• Soluble tablets are uncoated or film-coated tablets. They are intended to be dissolved in
water before administration. The solution produced may be slightly opalescent due to
the added excipients used in the manufacture of the tablets.
Dispersible Tablets
• Dispersible tablets are uncoated or film-coated tablets intended to be dispersed in water
before administration, giving a homogeneous dispersion.

12. Orodispersible Tablets
• Orodispersible tablets are uncoated tablets intended to be placed in the mouth where
they disperse rapidly before being swallowed.
Chewable Tablets
• Chewable tablets are intended to be chewed before being swallowed.
Tablets For Use In The Mouth
• Tablets for use in the mouth are usually uncoated tablets. They are formulated to effect a
slow release and local action of the active substance(s) or the release and absorption of the
active substance(s) at a defined part of the mouth.

13. Tablets administered by other routes
Implantation tablets:
• Depot tablets to be implanted subcutaneously under the skin for prolonged release
of the therapeutic agent. these tablets should be sterile.
Vaginal tablets:
• They are tablets prepared by compression intended to be inserted into the vaginal
cavity by special insertion device. It contains soluble substances with adjusted pH.

14. Ideal Tablet Characteristics
• Deliver the correct amount of drug in a proper form at or over proper time.
• Elegant free from defects like cracks, chips, contamination, discolouration
…etc.
• Maintain its chemical and physical integrity over time.
• should be capable to maintain the chemical and physical properties of the
therapeutic agent.
• Withstand the rigorous mechanical shocks during manufacturing, shipping
and storage.
• Release medicaments in the body in predictable and reproducible manner.

15. Tablet Ingredients
In addition to active ingredients, tablet contains a number of inert materials
known as additives or excipients.
Different excipients are:
1.Diluent
2.Binder and adhesive
3.Disintegrents
4.Lubricants and glidants
5.Coloring agents
6.Flavoring agents
7.Sweetening agents

16. Desired Properties of API
1. Purity :In accordance with the respective pharmacopoeia.
2. High stability
3. Compatibility with excipients: e.g primary amine and lactose.
4. Optimum bulk powder properties to have good flow, prevent
segregation and to optimize the tablet size.

17. Desired Properties of API -contd
4. Uniformity of particle size distribution to obtain uniformity in content,
uniformity in weight, disintegration time, friability, drying rate uniformity,
enhanced powder flow, good compression, regular dissolution and bioavailability.
• Fine particles increase surface area hence increases the surface energy giving
good compressibility.
5. Spherical shape provides good flow.
Irregular particle shape may lead to interlocking

18. Desired Properties of API -contd
6. Good powder flow: measured using angle of repose and can be improved by
addition of glidants, addition of fines, using wet granulation and increase the
density.
7.Optimum moisture content:
• lack of moisture in brittle tablets.
• increased moisture affects uniformity of content, make sticking and picking
• Moisture can be controlled by;
 Use of anhydrous salt
 Use of nonaquous solvent.
 Optimum drying time.
 Addition of adsorbent like Magnesium oxide.

19. Desired Properties of API -contd
8.Good compressibility.
• This is an intrinsic nature of elasticity, plasticity and brittle fracture of particles upon
compression.
9.Absence of static charges
• If any can be removed by granulation, addition of diluent or lubricant or
coating by colloidal silica.
10.Good organoleptic properties.
• Includes taste, smell, color.

20. Excipient Function
Diluent ( filler) Required bulk of tablet
Binder Provide necessary bonding to form granules
Disintegrant To bring disintegration within the specified time.
Lubricant To reduce friction in the die and ejection of tablet from the die cavity.
Antiadherent To prevent sticking of powder to the faces of punch and die.
Glidant Promote powder flow.
Wetting agent To aid disintegration
Buffer To improve stability and bioavailability.
Antioxidant To attain stability
Sweetening agent To enhance taste and mask bitter taste.
Preservative To prevent growth of microorganism
Color Disguise off color drugs, product identification and more elegant color
Flavor To improve odor and taste

21. Excipients – (selection based on)
• Toxicity.
• Availability.
• Compatibility.
• Stability.
• Bioavailability.
• Cost.

22. Diluents / Fillers
• Normally tablet size is more than 50 mg and diameter above 2-3 mm.
• Diluents are fillers used to make required bulk of the tablet when the drug
dosage itself is inadequate to produce the bulk.
• Fillers increase the bulk of the powder to produce the desired size.
• Secondary reason is to provide better tablet properties such as improve
cohesion, to permit use of direct compression manufacturing or to promote
flow.
• It constitutes 5 – 80% of the tablet weight.

23. General properties of diluents
• A diluent should have following properties:
1. They must be non toxic
2. There cost must be low
3. They must be physiologically inert
4. They must be physically & chemically stable by themselves & in combination with
the drugs.
5. They must be free from all microbial contamination.
6. They do not alter the bioavailability of drug.
7. They must be color compatible.

24. Types of diluents
1. Organic:
• Starch like directly compressed starch-Sta Rx1500
• Hydrolyzed starch-Emdex and Celutab.
• Mannitol, Sorbitol,Sucrose- Sugartab, DiPac, Nutab, Dextrose.
• cellulose derivatives like Microcrystalline cellulose-Avicel (PH 101and PH 102).
2. Inorganic:
• Calcium phosphates like dibasic calcium phosphatedehydrate, Calcium sulphate
dihydrate
3. Co- processed diluents-combining two or more materials by appropriate process.

25. Starch
• It is polysaccharide composed of amylose and amylopectin.
• Pregelatinised grade which provide free flow of powder.
• Used as a diluent, binder and disintegrant.
Mannitol
• Generally used for chewable tablets due to inherent sweetness and negative heat of
solution properties.
• Unlike sucrose it is free from grittiness.
• Most expensive sugar.

26. Celluloses – Microcrystalline cellulose MCC
• Highly compressible and widely used in direct compression.
• Hard tablet at low compression can be obtained.
• Fair flow.
• Binding and disintegration properties.
• Commonly used grades are Avicel pH 101, Avicel pH 102.

27. Calcium Phosphates
• Excellent compressibility and flow.
• Bulk density is higher.
• Hard tablets are obtained.
• Non – hygroscopic and inexpensive.
• Interact with some API such as Tetracycline.
• Dibasic calcium phosphate, dicalcium phosphate, calcium hydrogen phosphate dehydrate
tribasic calcium phosphate, tricalcium phosphate, tricalcium orthophosphate.

28. Binders – Adhesives
• These materials are added either dry or in wet- form to form granules or to form
cohesive compacts for directly compressed tablet.
• It can be termed as granulating agent.
• Generally binders are polymeric in nature.

29. Sugars Natural Synthetic / semisynthetic polymers
• Sucrose
• Liquid sucrose
 Acacia
 Tragacanth
 Gelatin
 Starch paste
 Pregelatinized starch
 Alginic acid
 Cellulose
Cellulose derivatives-
• Methyl cellulose,
• Hydroxy propyl methyl cellulose
• Sodium carboxymethylcellulose
• Gelatin- 10-20% solution
• Polyvinylpyrrolidone (PVP)- 2% conc.
• Starch paste-10-20% solution
• Sodium alginate
• Sorbitol
Types of binders

30. Characters of Commonly Used Binders
Binder Concentration Characters
Starch paste 5 – 25% w/w Freshly prepared paste.
Pregelatinized 5 – 10% w/w Starch that processed chemically and mechanically to rupture all or
part o
starch Direct compression granules in the presence of water then dried.
HPMC 2 – 5% w/w Can be used in either wet or dry granulation.
PVP 0.5 – 5% w/w added to powder blend in dry state then water is added
during granulation.
PEG 10 – 15% w/w Used as meltable binder. Anhydrous granulating agent. I improve
plasticity of other binders. Prolong disintegration time.

31. Methods of adding the binder
• As a dry powder mixed with the other ingredients before wetting.
• As a solution which is used as agglomerating liquid during wet agglomeration.
• As dry powder which is mixed with other ingredients before compaction.
( dry binder).

32. Disintegrants
• Bioavailability of a drug depends in its
absorption which is affected by its dissolution
and permeability across the GIT membrane.
• The rate of dissolution is greatly influenced by
the rate of disintegration.
• Disintegration must occur within the
specifications defined by the pharmacopoeia
(generally 15 minutes).
• Disintegrant was added to the formulation to
achieve this specification.

33. Mechanism of action of disintegrants
• Increase the porosity and wettability of the tablet matrix enabling the GIT fluids to penetrate
and there by enable tablet breakdown to occur.
Concentration 5 – 20%w/w.
Starch, corn and potato starches.
MCC Avicel 101 & Avicel 102. 10 -20% w/w.
Sodium starch glycolate5% w/w.

34. Mechanism of action of disintegrants
• Swelling of disintegrant in the presence of the aqueous fluid leading to tablet disintegration due
to increase in the internal pressure within the tablet matrix.
Sodium starch glycolate
Croscarmellose sodium 0.5-5% w/w.
Crospovidone 2 – 5% w/w.
Pregelatinized starch 5% w/w.
• Liberation of gas – Effervescent tablets.

35. Mode of addition of disintegrant
• Intragranular addition.
• In wet granulation method, the disintegrant is added to other excipients before wetting the powder with the
granulating fluid. Thereby, the disintegrant is incorporated within the granules.
• Extragranular addition.
• In both wet and dry granulation method, the disintegrant is added to the granules during dry mixing prior to
compression.
• It is proved that crospovidone is effective in improving the dissolution of the drugs in extra granular mode of
addition seems to be the best mode of incorporation, irrespective of the solubility of the main tablet component.
• 50% intragranular and 50% extragranular.
• In this method, disintegrant is divided into two portions.
• One portion is added before granule formation (intra) and remaining portion is added to granules (extra) with
mixing prior to compression. This method can be more effective.

36. FACTORS AFFECTING DISINTEGRATION
1. Effect of fillers:
soluble fillers increase the viscosity of the penetrating fluid which tend to reduce the effect of
the swollen disintegrating agent which tend to dissolve rather than disintegrate. Insoluble fillers
disintegrate more rapidly.
2. Effect of lubricants:
as lubricants are hydrophobic, they inhibit wetting and consequently disintegration of tablets.
Sod. starch glycolate remains unaffected as disintegrant.
3. Effect of binders:
Increase in the concentration of the binder increases the disintegration time.
4. Effect of Surfactants:
The speed of water penetration is increased by addition of surfactants.

37. Lubricants
.
• Lubricants are materials that acts at the interface between the surface of the tablet and the face
of die preventing the adhesion of the tablet material to the surface of the die and punsh
reducing the friction and facilitate ejection of the tablet from the die
Critical factors for optimizing lubricant function:
• Concentration of lubricant.
• Inadequate concentration result in tablet with pitted cavity surface and inability of tablet to
detach from the die.
• High concentration result in prolonged disintegration. Insoluble lubricant can be added at
the final mixing stage before compression.

38. Lubricants
• Stage and way of mixing. Mixing of lubricant with the disintegrant together lead to
• formation of lubricant film around the disintegrant which reduces the wettability and water
uptake by the disintegrant resulting in disintegration failure.
• Intensity and duration of mixing. Over mixing or high intensity of mixing result
disintegration and dissolution failure.
• Lubricant Particle Size. Smaller particle size enhance lubricant efficiency.

39. Commonly used lubricants
Material Concentration W/W Water Solubility
Magnesium stearate 0.25% - 0.5% Insoluble
Stearic acid 1% - 3% Insoluble
Glyceryl behenate 1% - 3% Insoluble
Glyceryl pamitostearate 1% - 3% Insoluble
PEG 4000 – 8000 mol.wt Soluble
Polyoxyethylene stearate 1% - 2% Soluble
Sodium lauryl sulphate 1% - 2% Soluble

40. Glidants
• They are water insoluble materials of a very fine particle size enhancing the powder flow
properties of the granules within the hopper into the tablet die by reducing the friction due
to their ability of particles to be located within the spaces between the granules.
• As they are almost hydrophobic, increase in concentration will reduce the
disintegration and dissolution time.
• Talc asbestos-free ( hydrated Magnesium silicate) is insoluble but not hydrophobic 5 – 30%
but its use was restricted because it will result in granuloma if inhaled.
• Colloidal Silicon Dioxide (Aerosil) 0.1 -0.5% w/w was used due to its hydrophobic properties
and fine particle size less than 15nm.

41. Coloring agents:
• The use of colors and dyes in a tablet has threepurposes:
(1)Masking of off color drugs
(2) Product Identification
(3) Production of more elegantproduct
• 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.
• 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

42. Flavoring agents:
• For chewable tablet- flavor oil areused
Sweeting agents :
To improve the taste and odour of the chewable tablets.
ExMannitol, lactose, sucrose and dextrose – saccharin, cyclamate,
aspartame.acv c

43. WETTING AGENTS
• Water molecules attract each other equally in all directions.
• The surface tension of water is strong enough to support the weight of tiny insects such as water
striders.
• The surface tension in action can be visualized by placing a small drop of alcohol on a thin
layer of water.
• Alcohol with lower surface tension mixes with water causing reduction in the surface tension
in the local region.
• Owing to the higher surface tension of water in the neighbor, water is pulled from the alcohol
dropped region into the neighbor, and this leads to the formation of a dry spot in the middle of
the water layer.

44. Manufacturing Process
• Wet granulation
• Dry granulation
• Direct compression

46. Powders intended for compression into tablets must
possess following essential properties
• Powder fluidity or flowability
• Powder compressibility
• Easily mixed with otherparticles
• Homogenous coloring etc
• Friction and adhesion properties

47. Wet granulation
The most popular method (over 70% ) granulation is done
 To prevent segregation of the constituents of the powder blend.
 To improve flowability of the powder mixture.
 To improve the compaction characteristics of the powder mixture due to better distribution
of the binder within the granules.
 To improve homogeneity and thus ensure content uniformity
Wet granulation is a process of using a solution binder to the powder mixture.
The amount of liquid can be properly managed;
overwetting = the granules to be too hard,
underwetting =too soft and friable.

48. Wet Granulation
Step 1: Weighing and Blending
Step 2: wet granules prepared by adding the bindersolution
Step 3: Screening the damp mass into pellets or granules (6- 8mesh)
Step 4: Drying the granulation in thermostaticallycontrolled ovens
Step 5: Dry screening:
Step 6: Mixing with other ingredients: A dry lubricant, antiadherent and glidant is added to the
granules either by dusting over the spread-out granules or by blending with the granules. Dry
binder, colorant or disintegrant may be also added in this step.
Step 7: Tableting: Last step in which the tablet is fed into the die cavity and thencompressed.

49. Wet granulation stage 1, Mixing
• Drug and excipients excluding lubricants.
• Mixing time and speed should be enough to produce homogeneous mixture.
• Planetary bowel mixer.
• Rotating drum mixer.
• High-speed mixers.
• Ribbon / trough mixers.

50. Planetary bowel mixer
• The mixing shaft rotate around the bowel and
around itself.
• Planetary like movement.
• Material used is stainless steel

51. Rotating drum mixer.
( double cone)
• The mixing shaft rotate and hence the drum is
rotated.
• Material used is stainless steel

52. Ribbon / trough mixer
• Mixing blades.
• Material used is stainless steel

53. Rapid mixer granulator
• Rapid mixer granulator is a mixing unit with a bottom
entry agitator and side mounted chopper for
granulation.
• Can be used for dry blending, wet mixing and
granulation.
• The principle is agitation of the content at moderate
speed and then running the cutting blade at high
speed.
• Dry mixing 3-5 min, wet mass 5- 10 min then 5-10
min to produce 0.5 – 1.5 mm granules.

54. Wet granulation stage 2,Wet granules formation
• Fluid simultaneously incorporated in the powder mix.
• Granulation fluids are water, isopropanol, ethanol or mixture.
• The binder is either incorporated in the solid state within the powder mix or dissolved in
the granulation fluid.
• Wet Granulation Techniques
A- Oscillating granulator
B- Fluidized bed granulation
C- Extrusion spheronization
D- Rapid mixture granulator RMG
E. Spray drying granulation.

55. Oscillating granulator
• Low sheer is used
• The binder in the granulating fluid is added
whilst maintaining mixing.
• The wetted powder mass is then passed into an
oscillating granulator which forces the powder
mass through a metal screen under the action
of an oscillatory stress.

56. Fluidized bed granulator
• The powder is suspended by vertical flow of
air from the bottom of the granulator.
• The granulation fluid is sprayed on the
powder from the top of the granulator.
• Tangential air flow provides circular powder
suspension.
• Air applied with controlled
temperature.

57. Extruder
• Premixed powder to which the granulation fluid
being added is placed into the barrel of the
extruder via hopper.
• In the barrel the wet mass moves horizontally
via single or twin screws from the hopper end
by a turning motion.
• Passed through a perforated plate into lengths.
• The extruded strands should break to produce
granules of uniform particle size.

58. Drying of the granules
1. Tray dryer: Traditional oven . Wet granules are placed horizontally in a shallow plates. Air
entered the drier warmed by heaters. Vacuum can be applied. Condensed water is collected and
disposed.
2. FBD: often used in the industry and having the advantages of:
1. Excellent heat transfer and rapid in action.
2. Accurate control of the drying conditions.
3. And of limitation:
4. Attrition of granules.
5. Powder waste.
6. Development of static electricity .
3. Freeze drying, microwave dryer, spray dryer.

59. Milling of the granules ( Resizing)
• Toproduce the required particle size and distribution to
improve the flow of powder into the die and its filling.
The granule size decreases as the tablet size decreases.
• Size reduction methods includes:
• Oscillating granulator
using defined mesh.
• Quadro Comil
conical chamber containing defined mesh . Granules
pass through the screen in a centrifugal manner by the
action of rotating impeller.

60. Incorporating the lubricant
• Mixing the lubricant with the dried granules usually takes place in the same mixing
equipment used in the first stage.
• Noted that the time of mixing and the shear rate are crucial.

61. Granules formation
• Particle –particle interactions
facilitated by the formation of
liquid bridges.
• Pendular state.
• Funicular state
• Capillary state
• Overwetted state

62. Granule formation

63. Granules formation - contd
• Particle – Particle interactions facilitated by the formation of solid bridge.
• They are formed from the polymeric binder following drying.
• These bridges contribute to the mechanical properties of the resulting
granules.
• Crystallization of the binder followed by crystallization of the water
soluble drug may affect directly the quality of produced tablets.( sugars)

64. Advantages of wet granulation
• Reduce segregation during process and storage leading to intra and
interbatches variations.
• Useful for tablets contain low concentration of therapeutic agent.
• Employs conventional excipients.
• Most plants had been built around wet granulation.
• Tablets produced have good mechanical strength and hence can withstand coating
and packing procedures.

65. Disadvantages of wet granulation
• Several process steps.
• Presence of solvent lead to:
• In materials having susceptibility to Hydrolysis.
• Soluble drugs may crystallize during drying.
• Heat to remove the solvent make the process expensive.
• Thermally labile therapeutic agents may undergo degradation.
• Issues regarding the use of alcohol if used.

66. DRY GRANULATION
SUTIABLE FOR
• For thermolabile material
• For materials that can be affected by solvent
• Ingredient having enough cohesive properties.
METHODS FOR DRYGRANULATION
• Slugging
• Roller compaction.

67.  On a large scale compression granulation can also be performed on a rollercompactor.
 Granulation by dry compaction can also be achieved by passing powders between two rollers
that compact the material at pressure of up to 10 tons per linear inch.
 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 aluminum
hydroxide.
 Roller compactor is capable of producing as much as 500 kg/hr of compacted ribbon like
materials which can be then screened and milled in to granules for compression.
Dry compaction/Rollercompaction

69. Mechanism of granules formation in drygranulation
• Electrostatic forces.
Initial cohesive interaction between particles.
• Van der Waals interactions
Van der Waals forces increases as the distance between the particles decreases.
• Melting of components within the powder mix
Due to partial melting of excipients upon cooling solidification occur
resulting in increased interactions between adjacent particles.

70. Advantage of dry granulation
• Soft tablet incapable for further
processing like coating.
• Dust generation and powder loss.
• Segregation of components may occur
post mixing.
• Special equipment required.
• Problems with powder flow.
• No need for special excipients
• No heat , no solvent
• No change in the morphology of
ingredients.
Disadvantage of dry granulation

71. Direct compression
• Mixing and subsequent compression.
• Interactions of particles are similar to dry granulation.
• To obtain same and uniform particle size of ingredients, this may require milling.
• Ball mill
• Hammer mill
• Fluid energy mill
• Mixing in the same mixers as wet granulation.

74. Colloidal mill
Fitzmill

75. Advantages of DC
• Fewer processing steps and cost effective.
• No use of water or solvent, no heat so
produce more stable product and lessens
the cost.
• Lubricant is incorporated in the same
vessel.
1. Similar particle size and density for the excipients
and the therapeutic agent are required to
minimize segregation.
2. Powder flow within the tableting machine.
3. Tablets produced are soft making it difficult for
further processing.
4. If the API is more than 10%, it will affect
compressibility.
5. Colorants could not be used.
6. Dust and waste.
Disadvantages of DC

77. Compression Tools
Die

78. Stages of compression
• Stage1 : Filling the die with the granules / powder:
• The powder or granules are fed from the hopper of machine into the die filling
the space between the lower and upper punches.
• The space is determined by the position of the lower punch which can be altered
to increase or decrease the tablet size.

79. Stages of compression
• Stage2 : compression ofthe granules / powder bed:
• Retraction of the shoe.
• Upper punch descend and compress the powder.

80. Stages of compression
• Stage 3 : Tablet ejection:
• Upper punch is elevated to its original position.
• The lower punch moves upwards until it flush with the die plate.
• The shoe moved across the die plate where it pushes the tablet from the lower
press.
• The lower punch returns to its original position to start new cycle.

81. Types of Tablet Presss
• Single-Punch tableting
Machines
• This tablet press composed of
only one set of punches and die.
• Used in pilot- scale
manufacturing and in R&D or in
dry granulation (slugging)
• Speed is up to 200 tablets per
minute.

82. Rotary Tablet Press
Single rotary tablet machine
High speed double rotary
rotary tablet machine

83. Rotary Tablet Press
• For large scale , produce up to 10,000 tablet per minute.
• Have up to 60 sets of punches and dies.
• Dies table rotate in a circular motion.
• Lower and upper Punches being held by the turrets are lowered and elevated by an upper and
lower rollers.
• The powder l granules are fed from the hopper on the upper surface of the die table. Then
transported by a feed frame into the die, where they are subsequently compressed by the
simultaneous movement of the upper and lower punches.
• The tablets are removed from the rotating die table into a chute from which they are collected.

84. Rotary Tablet machine

85. Rotary tablet press

86. Concept pf tablet compression

87. Compression Cycle
1. Powder or granules fed to the hopper, emptied into the feed frame by gravity.
2. The interconnected compartments of the feed frame spread the powder over the area and fill the dies.
3. The pull down cam guide the lower punches downwards allowing dies overfill.
4. Punches pass over a weight-control cam, which reduces the fill into the dies to the desired amount.
5. A wipe off blade at the end of the feed frame removes the excess.
6. The lower punches move over the lower compression roll while the upper punches ride beneath the upper
compression roll and enter into the dies while the lower punches are raised to squeeze the powder within the die.(
moment of compression)
7. The upper punches are withdrawn following the upper cam, the lower punches ride up the lower cam bringing the
tablets up the surface of the dies.
8. The tablet strike the sweep off blade in front of the feed frame and slide it down the chute into the container.

88. Capping
Lamination
Cracking
Chipping
Picking
Sticking to die surface
Pitting
Binding
Mottling
Double impression

89. • The upper or the lower segment of the table separates
horizontally, either partially or completely.
• Causes may be either due to the formulation or due to
machine.
Reason:
Air entrapped in compact during compression and
subsequent expansion on ejection from the die or
handling.

90. Causes Remedies
Large amount of fines in the granulation. Remove fines through 100 -200 mesh
screen.
Too dry or very low moisture leading to
loss of binding action
Moist the granules or add hygroscopic
e.g sorbitol, PEG 4000.
Not thoroughly dried granules. Dry the granules properly
Insufficient or improper binder Increase or change binder.
Insufficient or improper lubricant Increase or change lubricant
Granular mass too cold to compress Compress at room temperature.

91. Causes Remedies
Poorly finished dies. Polish dies properly
Deep concave punches or beveled edge
faces of punches
Use flat punches
Lower punch remain below the level of the
die plate during ejection
Make proper setting
Incorrect adjustment of sweep-off blade Adjustment of ejection blade.
High turret speed Increase dwell time

92. • Tablet may undergo separation into two or more horizontal
layers.
• Causes may be either due to the formulation or due to machine.
Reason:
Air entrapped in compact during compression and subsequent
release on ejection. The condition exaggerated by higher speed
of turret.

93. Causes Remedies
Oily or waxy materials granules - Modify mixing process
- Add adsorbent or absorbent
Too much of hydrophobic lubricant e.g
Magnesium stearate
- Decrease the amount or change the
lubricant.
Lamination due to machine causes and its remedies
Rapid relaxation of the peripheral regions
of the tablet, on ejection from a die
- Use tapered die , upper part of the die
bore has an outward taper of 3 -5˚
Rapid decompression
- Use precompression step .
-Reduce turret speed and reduce the final
compression pressure.

94. • Small cracks on the centre of the upper or lower
surfaces.
• Causes may be either due to the formulation or due to
machine.
Reason:
Rapid expansion of tablet especially when deep concave
punches are used.

95. Causes Remedies
Large size of granules - Reduce granules size
- Add fines
Too dry granules - Moisten the granules properly
- Add proper amount of binder
Tablets expand - Improve granulation
- Add dry binder
Too cold granulation Compress at room temperature.
Cracking due to machine causes and its remedies
Tablet expand on ejection due to air entrapped
Deep cavities cause cracking while removing
tablets
-Use tapered die , upper part of the die bore
has an outward taper of 3 -5˚
- Use less concave punches.
- Use gentle take-off ejection device.

96. • Tablet material adhere to the punch.
• Causes may be either due to the formulation or due to machine.

97. Causes Remedies
Moist granules Determine optimum time for drying
Insufficient or improper lubricant - Increase lubrication
- Use colloidal silica as polishing
Low melting point of substance Use high melting point materials
Too warm granules Cool the system
Excess binder Reduce or change the binder

98. Causes Remedies
Rough or scratched surface of punch Polish punch face properly
Imposing or engraving letters Design letters as large as possible
Too deep dividing line or bevels Reduce depth and sharpness
Insufficient pressure Optimize the pressure

99. • Tablet material adhere to the die faces. Filming is a slow form of sticking due to
excess moisture.
• Causes may be either due to the formulation or due to machine.
• Reason:
• Improperly dried or improperly lubricated granules

100. Causes Remedies
Moist granules, hygroscopic material Determine optimum time for drying,
control humidity
Insufficient or improper lubricant - Increase lubrication
- Use colloidal silica as polishing
Too much binder Decrease or change the binder
Oily or waxy material Modify mixing process, add adsorbent
Too soft or weak granules Optimize binding , change granulation
technique.

101. Causes Remedies
Rough or scratched surface of die Polish die face properly
Die design Use tapering dies
Too fast speed Reduce speed
Insufficient pressure Optimize the pressure

102. • The tablet adhere or tear in the die. A film is
formed un the die and ejection is hindered.
Tablet edges are cracked.
• Causes may be either due to the formulation or
due to machine.
Reason:
Excessive moisture, lack of lubricant, worn
dies

103. Causes Remedies
Too moist granules expanded around the lower
punch
Optimum drying
Insufficient or improper binder Increase of change lubricant
Too large granules
Reduce the size or add fines or add
more lubricant
Too hard granules for the lubricant to beeffective
Reduce granular size or modify the
granulation method
Too abrasive granules and cutting into the die Reduce granular size
Granular mass too warm stick to the die during
compression
Reduce temperature

104. Causes Remedies
Poorly finished dies. Polish dies properly
Rough dies due to abrasion or corrosion Change dies
Undersized dies Use proper die size
Too much pressure Reduce pressure or modify granulation

105. • Pit marks on the surface of the tablet
• Corrected by polishing the punch surface and
increasing the lubricant, its time and rate of mixing.
Reason:
Rough surface of the punch or insufficient lubricant

106. • Sticking of the tablet to the die and do not eject properly.
• Causes and remedies are the same as chipping.
Reason:
Excessive moisture, insufficient lubrication or use of worn
die

107. • Uneven distribution of colour with black or light spots
in the surface.
• May be due to the formulation or the tableting
machine.
Reason:
Spotted colouration on the surface of the tablet.

108. Causes Remedies
A coloured drug used with white excipients. Use appropriate colouring agent
A dye migrate to the surface of the granules
during drying
- Change the solvent & binder
- Reduce the drying temp
- Use smaller particle size
Improperly mixed dye - Reduce size and mix properly
Improper mixing of coloured binder Incorporate dry color during blending
then add dry binder, mix then add the
granulating fluid.
Waxes and oils of machine parts lubrication - Check the seals
Dust - Clean and clear the environment

109. • It takes place in only those punches having engraving.
• At the moment of compression, the tablet receives the imprint, the upper or
lower punch rotate freely and travelling a distance which may result another
contact with the tablet resulting in double impression.
• Revise setting of machine and tie the punch by tooling key.
• Use punches with male and female anti-turning lock to prevent rotation.
Reason:
• Free rotation of either the lower or upper punches during ejection of tablet.

110. Tablet Coating
• PURPOSES OF TABLET COATING
1. Toprevent degradation in the stomach
– ( enteric coating )
2. Toprevent drug induced irritation at the
stomach-( NSAID)
3. Toprovide controlled release of the drug
throughout the GIT.
4. Totarget drug release at specific site in the GIT.
Tomask the taste of the drug.
5. Toimprove the appearance of tablet.
6. Toprotect the tablet – shelf-life & stability
• TYPES OF TABLET COATING
PROCESS
1. Sugar Coating
2. Film Coating.
3. Press Coating
• TYPES OF COATING EQUIPMENTS
1. Standard coating pan
2. Perforated coating pan
3. Fluidized bed ( air suspension)
coaters.

111. • Coloured or uncoloured of
sucrose - based layer around the
tablet.
• Improve the appearance and mask
the taste.
• Insulate the tablet.
• Dramatically decreased practice
due to advantages of film coating.
Conventional Pan

112. Process of sugarcoating
• Stages of process:
1. Sealing of tablet cores.
2. Sub-coating
3. Smoothing
4. Colouring
5. Polishing
6. Printing
• General description of the process:
1. Tablets are placed in the coating pan and agitated.
2. The coating solution is sprayed on the surface of
the tablets.
3. Warm air is passed over the tablets to facilitate
removal of the solvent.
4. When solvent has evaporated, the tablets will be
coated with the solid components of the coating
solution.

113. 1-Sealing of tablet cores.
• An insoluble impermeable polymer solution is applied to seal
the tablet against entry of water.
1. Shellac
2. Cellulose acetate phthalate
3. Polyvinylacetate phthalate
4. Hydroxypropylmethyl cellulose

114. 2-Subcoating
Gelatin
Acacia
Sub-coating solution
6% W/W 3.3 % W/W
8 7.7
Sucrose 45 55.3
Distilled To 100 To100
water
Sub-coating suspension
40% W/W
20
Sucrose
Calcium
carbonate
Talc 12
Gum acacia 2
Titanium dioxide 1
Distilled water 25
1. Applying the gum based solution followed by sucrose
based powder then drying.
2. Application of a suspension powder in gum-sucrose
solution
3. Powders as Calcium carbonate or Talc.

115. 3- Smoothing
• Rough surface can be smoothened by application of few coating
layers of simple syrup.
• The simple syrup may contain starch, acacia, gelatin and pacifier.

116. 4- Colouring
• Application of several layers of colour solution in 60 – 70%
sucrose syrup.
• Colours should be approved by the regulatory authority.
• Predispersed lake ( pigment) is superior because:
1. The colour is water insoluble.
2. It is opaque.
3. Maintenance of batch to batch colour.
4. Reduction in the overall process time.
5. Reduction in the thickness of the colour coating layer.

117. 5- Polishing
• Commonly used method is an application of organic solvent to
get suspension or solution of waxes.
• Carnauba wax
• Beeswax
• An emulsion may be used and stabilized by acceptable
surfactant.
• Other methods involves the use wax-lines pan and use finely
powdered wax application.
• Mineral oil application.

118. 6- Printing
• Why sugar coated tablets requires printing for and not
other method for identification?
• Edible pharmaceutical ink formulation:
• Shellac
• Alcohol
• Pigment
• Lecithen
• Antifoam
• Organic solvent

119. Film Coating
• A deposition of a thin film layer of polymer or mixture of polymers
around the conventional tablets core.
• Polymers that are used in film coating which dissolve in the stomach
to enable disintegration and dissolution :
• Hydroxypropylmethyl cellulose.HPMC
• Hydroxypropyl cellulose HPC
• Eudragit E 100
• Target drug release film coated tablets are coated by insoluble
• Ethylcellulose.
• Eudragit RS & RL

120. Comparison between Sugar & Filmcoating
Features Sugar coating Film coating
Appearance Rounded with degree
polish
of Retains contour of the original
tablet – not shiny
Weight increase 30 – 50 % 2 – 3 %
Logo or break-lines Not possible Possible
Other dosage form Of no industrial
importance
possible - multiparticulates
Stages of process Multistage process Single
Batch coating time 8 hours 2 hours
Functional coating Generally not practical Controlled release

121. Advantages of Film coating
• Elegance and glossy appearance.
• Maintain the logo and break line.
• Improve mechanical strength an integrity and improve
resistance for handling and shipping.
• Flexibility in types of formulation.
• Minimal weight increase.
• Less time consuming.
• Minimize dust.
• Automated equipment are used.
• Single process and not rquires excessive training.

122. Formulation of the coating fluid
Polymer ( may be enteric or non-enteric)
Plasticizer
Colorant
Opaquant – extender
Solvent