Tablets by Ms. Bansari B. Patel (Assistant Professor)

Tablets
Prepared By:
Ms. Bansari B. Patel

Introduction
 Most of the medicaments prefer the oral route of administration due to the several advantages as
compared to the other dosage form.
 According to USP, 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 shape and differ greatly in size or weight, depending on amount of medicinal
substances and the intended mode of administration.
 It is the most popular dosage form and around 70% of medicines are dispensed in the form of the
tablet.

Advantages of tablet dosage form
 From the standpoint of manufacturer:
 An accurate amount of medicament, even if very small, can be incorporated.
 Tablets provide best combined properties of chemical, mechanical and microbiological
stability of all the oral dosage forms.
 Since they are generally produced on a large scale, therefore, their cost of production is
relatively low, hence economical.
 They are in general the easiest and cheapest to package and ship among all oral dosage
forms.
 Some specialized tablets may be prepared for modified release profile of the drug.
 Product identification is potentially the simplest and cheapest requiring no additional
processing steps when employing an embossed or monogrammed punch face.

Cont…
 From patients stand point:
 They are easy to carry, easy to swallow and they are attractive in appearance.
 Unpleasant taste and odor can be masked by coating and they do not require any
measurement of dose.
 Some of the tablets are divided into halves and quarters by drawing lines during
manufacturing to facilitate breakage whenever a fractional dose is required.

Disadvantages of tablet dosage form
 Difficult to swallow in case of children and unconscious patients.
 Drugs with poor wetting, slow dissolution properties, optimum absorption high in GIT may
be difficult to formulate or manufacture as a tablet that will still provide adequate or full
drug bioavailability.
 Bitter tasting drugs, drugs with an objectionable odor or drugs that are sensitive to oxygen
may require encapsulation or coating. In such cases, capsule may offer the best and lowest
cost.
 Increase product loss due to multilevel processes during manufacturing.
 Absorption of drug depends on various physiological characteristics like gastric emptying
and it varies from one patient to another.
 Some drugs resist compression into dense compacts, owing to amorphous nature, low
density character.

Ideal properties of tablets
 A tablet should have elegant product identity while free of defects like chips, cracks,
discoloration, and contamination.
 Should have sufficient strength to withstand mechanical shock during its production
packaging, shipping and dispensing.
 Should have the chemical and physical stability to maintain its physical attributes over time
 The tablet must be able to release the medicinal agents in a predictable and reproducible
manner.
 Must have a chemical stability over time so as not to follow alteration of the medicinal
agents.

Types of tablets
A. Tablets ingested orally:
1. Compressed Tablets, e.g.: Paracetamol Tablets
2. Multiple Compressed Tablets, e.g.: Disprin Tablets
3. Coated Tablets
a. Sugar coated tablets, e.g.: Ibuprofen Tablets
b. Film coated tablets, e.g.: Erythromycin, Valsartan
4. Modified Release Tablets
5. Delayed Release Tablets
6. Chewable Tablets
B. Tablets used in oral cavities
1. Buccal Tablets
2. Sublingual Tablets
3. Lozenges
4. Dental cone

Cont…
C. Tablets meant to be formulated in solution
1. Effervescent tablets
2. Dispensing tablets
3. Hypodermic tablets
4. Tablet triturates
D. Tablets administered by other route
1. Implantation tablets
2. Vaginal tablets

Cont…
 Tablets ingested orally:
 Compressed tablets:
 These tablets are formed by compression and contain no special coating.
 They are made from powdered, crystalline or granular materials, alone or in combination with
suitable excipients.
 These tablets contain water soluble drugs which after swallowing get disintegrated in the stomach and
its drug contents are absorbed in the gastrointestinal tract and distributed in the whole body. e.g.
Aspirin (Disprin) paracetamol tablets (Crocin).

Cont…
 Multiple compressed tablets:
 These are compressed tablets made by more than one compression cycle.
 Such tablets are prepared by compressing additional tablet granulation on a previously
compressed granulation.
 The operation may be repeated to produce multilayered tablets of two or three layers.
 To avoid incompatibility, the ingredients of the formulation except the incompatible
material are compressed into a tablet and then incompatible substance along with necessary
excipients are compressed over the previously compressed tablet.

Cont…
 Coated Tablets:
 Sugar coated tablets:
 These are compressed tablets containing a sugar coating.
 Such coatings are done to mask the bitter and unpleasant odour and the taste of the
medicament.
 The sugar coating makes the tablet elegant and it also safeguard the drug from atmospheric
effects.

Cont…
 Film Coated Tablets
 The compressed tablets having a film coating of some polymer substance, such as hydroxy
propyl cellulose, hydroxy propyl methyl cellulose and ethyl cellulose.
 The film coating protects the medicament from atmospheric effects. Film coated tablets are
generally tasteless, having little increase in the tablet weight and have less elegance than
that of sugar coated tablets.

Cont…
 Modified Release Tablets:
 This type of tablets are formulated to dissolve a drug over time in order to be released slower
and steadier manner.
 Modified release tablets may be of different kind.
 Sustained release
 Extended release
 Prolonged release
 Timed release

Cont…
 Delayed release tablets:
 The term delayed release can be used
interchangeably with site specific drug
delivery.
 Enteric coated tablet are a type of delayed
release tablets.
 These are compressed tablet meant for
administration by swallowing and are
designed to by-pass the stomach and get
disintegrated in the intestine only.
 These tablets are coated with materials
resistant to acidic pH (like cellulose acetate
phthalate, CAP) of the gastric fluid but get
disintegrated in the alkaline pH of the
intestine.

Cont…
 Chewable Tablets:
 These are the tablets which are required
to be broken and chewed in between the
teeth before ingestion. These tablets are
given to the children who have difficulty
in swallowing and to the adults who
dislike swallowing.
 These tablets should have very
acceptable taste and flavor. Ex- Antacid
tablets (Digene).

Cont…
 Tablets used in oral cavity:
 Buccal Tablets:
 These tablets are to be placed in the side of the cheek (buccal pouch) where they dissolve
or erode slowly and are absorbed directly in the buccal cavity without passing into the
alimentary canal.
 Therefore, they are formulated and compressed with sufficient pressure to give a hard
tablets. e.g. Progesterone tablets.

Cont…
 Sublingual tablet:
 These tablets are to be placed under the tongue where they dissolve or disintegrate quickly
and are absorbed directly without passing into GIT. e.g. tablets of .

Cont…
 Lozenges:
 These tablets are designed to exert a local
effect in the mouth or throat. These tablets
are commonly used to treat sore throat to
control coughing in common cold.
 They may contain local anesthetics,
antiseptics, antibacterial agents and
astringents.
 These are prepared by compression at a high
pressure by the molding process and
generally contain a sweetening agent,
flavoring agent and a substance which
produces a cooling effect. e.g. Vicks
lozenges, Strepsils.

Cont…
 Dental Cones:
 These are compressed tablets meant for
placement in the empty sockets after
tooth extraction.
 They prevent the multiplication of
bacteria in the socket following such
extraction by using slow-releasing
antibacterial compounds or to reduce
bleeding by containing the astringent.

Cont…
 Tablets used to prepare solution:
 Effervescent tablets:
 These tablets along with the active
medicament contain ingredients like sodium
bicarbonate, citric acid and tartaric acid
which react in the presence of water
liberating carbon dioxide and producing
effervescence leading to disintegration of
the tablet, thus fastens solution formation
and increase the palatability. E.g. Histac
(Ranitidine)

Cont…
 Dispensing tablets:
 These tablets provide a convenient quantity of potent drug that can be readily
convert into powders and incorporate into liquids.
 They are to be added to water or other suitable solvent to make a solution
containing a fixed concertation of API.
 It should not contain insoluble materials as they are to be converted into clear
solution.
 These tablets are highly toxic if taken orally by mistake.

Cont…
 Hypodermic tablets:
 Hypodermic tablets are soft, readily soluble tablets and originally were used for the
preparation of solutions to be injected.
 These tablets are dissolved in sterile water or water for injection and administered by
parenteral route. these tablets are not preferred now-a-days because the resulting solution is
not always sterile.

Cont…
 Tablet Triturates:
 These are powders molded into tablets. They are flat, circular discs, usually containing a
potent substance mixed with lactose, lactose and sucrose, dextrose, or other suitable
diluent.
 Since they are intended to disintegrate very quickly in contact with moisture, water
insoluble adjuncts are avoided. The name ‘tablet triturate’ is appropriate because they
usually contain trituration (trituration = dilution with an inert substance).

Cont…
 Tablets administered by other routes:
 Implantable tablets:
 These tablets are placed under the skin or inserted subcutaneously by means of
minor surgical operation and are slowly absorbed. These may be made by heavy
compression but are normally made by fusion.
 The implants must be sterile and should be packed individually in sterile
condition. Implants are mainly used for the administration of hormones such as
testosterone steroids for contraception.
 These tablets are very usefully exploited for birth control purpose in human
beings.

Cont…
 Vaginal Tablets:
 These tablets are meant to dissolve slowly in the vaginal cavity. The tablets are typically
oval or pear shaped for the ease of insertion. these tablets are used to release steroids or
antimicrobial agents.
 The tablets are often buffered to promote a pH favorable to the action of a specified
antimicrobial agent. The contains easily soluble components like lactose or sodium
bicarbonate.

Tablets excipients
 In addition to active ingredients, tablet contains a number of inert materials known as
additives or excipients. Different excipients are:
1. Diluent / Filler
2. Binders and adhesive
3. Disintegrants
4. Lubricants and glidants
5. Coloring agents
6. Flavoring agents and Sweetening agents

Function of excipients
 Impart weight, accuracy, & volume.
 Improve solubility
 Increase stability
 Enhance bioavailability
 Modifying drug release
 Assist product identification
 Increase patient acceptability

Diluents:
 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.
 Diluent should have following properties:
 They must be non-toxic and low cost.
 They must be commercially available in acceptable grade
 They must be physiologically inert, physically & chemically stable by themselves & in
combination with the drugs.
 They must be free from all microbial contamination.
 They do not alter the bioavailability of drug.
 They must be color compatible.

Cont…
 Commonly used tablet diluents-
 Lactose-anhydrous and spray dried lactose
 Directly compressed starch-Sta Rx 1500
 Microcrystalline cellulose-Avicel (PH 101and PH 102)
 Dibasic calcium phosphate dehydrate
 Calcium sulphate dihydrate
 Mannitol and Sorbitol
 Sucrose- Sugartab, DiPac, Nutab
 Dextrose

Cont…
 Lactose
 Lactose is the most widely used diluent for tablet formulation.
 It is obtained in hydrous and anhydrous form.
 The anhydrous form, picks up moisture when exposed to elevated humidity. Such tablets
should be packed in moisture proof packets or containers.
 When a wet granulation method is employed, the hydrous form of lactose should generally
be used.
 Two grades of lactoses are commercially available:
 60 to 80 mesh – coarse
 80 to 100 mesh – regular grade

Cont…
 Advantages:
 Lactose has no reaction with most of the drugs, whether in hydrous or anhydrous form.
 Lactose formulations show good release rates.
 Their granulations are readily dried, and the tablet disintegration times of lactose tablets
are not strongly sensitive to variations in tablet hardness.
 It is a low cost diluent.
 Disadvantages:
 Lactose reacts with amine drug bases in presence of alkaline lubricants e.g. metal stearates
(e.g. magnesium stearate) and gradually discolours (dark brown) with time due to the
formation of furaldehyde. This reaction is called Maillard reaction.

Cont…
 Calcium salts ((DCP/TCP)
 Dibasic calcium phosphate dihydrate (or dicalcium orthophosphate) (DCP) [CaHPO4.2H2O],
Calcium sulfate dihydrate (CaSO4.2H2O).
 Advantages:
 Diluents that exist in their common salt form as hydrates, containing appreciable bound water as
water of crystallization. This bound water of calcium sulfate is not released below 800oC. They
possess very low concentration of unbound moisture. Hence, these salts are excellent diluents for
water-sensitive drugs. It is superior to anhydrous diluent, which has a moderate to high moisture
demand.
 Disadvantages:
 Tetracycline products made with calcium phosphate diluent had less than half the bioavailability of
the standard product. Divalent cation (Ca++) form insoluble complexes and salts with number of
amphoteric or acidic functionality antibiotics, which generally reduces their absorption (which is
also why milk should not be co-administered with these drug).

Cont…
 Spray dried lactose
 Advantages:
 It is used for direct compression (containing drug + diluent + disintegrant + lubricant).
 In addition to the direct compression properties, spray dried lactose also has good flow
characteristics. It can usually be combined with as much as 20 to 25% of active ingredients
without losing these advantageous features.
 Disadvantages:
 If spray dried lactose is allowed to dry out and the moisture content falls below the usual
3% level, the material loses some of its direct compressional characteristics.
 Spray-dried lactose is especially prone to darkening in the presence of excess moisture,
amines, and other compounds owing to Maillard reactions. Hence, a neutral or acid
lubricant should be used.

Cont..
 Directly compressible starches
 Sta–Rx 1500– free flowing, directly compressible starch. It is used as diluent,
binder, disintegrant.
 Emdex and Celutab – are two hydrolyzed starches – contains dextrose 90–92%
and maltose 3–5% free flowing and directly compressible and may be used in
place of mannitol in chewable tablets because of their sweetness and smooth
feeling in the mouth.
 Dextrose (D–Glucose)
 Available in two forms: as hydrates and anhydrous forms.
 Dextrose may sometimes be combined in formulation to replace some of the spray
dried lactose, which may reduce the tendency of the resulting tablets to darken.

Cont.…
 Mannitol
 Advantages
 Because of the negative heat of solution (cooling sensation in the mouth) its slow solubility,
and its pleasant feeling in the mouth, it is widely used in chewable tablets.
 It is relatively non-hygroscopic and can be used in vitamin formulations.
 Low calorie content and non-carcinogenic.
 Disadvantages
 Costly and has poor flow characteristics and usually require fairly high lubricant level.
 Sorbitol
 It is an optical isomer of mannitol and is sometimes combined with mannitol formulations to
reduce the diluent cost.
 Disadvantages:-
 It is hygroscopic at humidities above 65%.

Cont…
 Sucrose
 Some sucrose based diluents are:
 Sugar tab– 90 to 93% sucrose + 7 to 10% invert sugar
 Di Pac – 97% sucrose + 3% modified dextrins
 Nu Tab– 95% sucrose + 4% invert sugar + small amount of corn starch + Mg-stearate
 Advantages:
 They are all used for direct compression.
 Disadvantages:
 All are hygroscopic when exposed to elevated humidity.
 Microcrystalline cellulose (MCC)
 Trade Name : Avicel – is a directly compression material
 Two grades are available PH 101-powder PH 102- granules
 Advantages: It acts as diluent and disintegrating agents.

Binders and adhesives
 Agents used to impart cohesive qualities to the powdered material are referred to as binders
or granulators.
 Objective of incorporating binders
 They impart a cohesiveness to the tablet formulation (both direct compression and wet–
granulation method) which insures the tablet remaining intact after compression.
 They improves the free-flowing qualities by the formation of granules of desired size and
hardness.

Cont…
 Incorporation of Binder:
 Method-I
 Binders are used in dry form in the powder and then moistened with a solvent (of the
binder) to form wet lumps.
 Method-II
 Binders are often added in solution form. It requires lower concentration of binder.
 By Method-I the binder is not as effective in reaching and wetting each of the particles
within the mass of the powder.
 Method-III
 In direct compression method MCC, microcrystalline dextrose, amylose and PVP are used
those have good flow property and cohesiveness as well.
 It has been postulated that MCC is a special form of cellulose fibril in which individual
crystallites are held together largely by hydrogen bonding. The disintegration of tablets
containing the cellulose occurs by breaking intercrystallite bonds by the disintegrating
medium.

Cont…
 Starch paste
 Corn starch is often used in the concentration of 5-10%.
 Method of preparation:-
 Corn starch is dispersed in cold purified water to make a 5 to 10% w/w suspension and
then warming in water both with continuous stirring until a translucent paste is
formed.. (Actually hydrolysis of starch takes place.)
 Liquid glucose:-
 50% solution in water is fairly common binding agent.
 Sucrose solution:-
 50% to 74% sugar solution is used as binder. They produce hard but brittle granules. Their
cost is low.

Cont…
 Gelatin solution
 Concentration 10–20% aqueous solution
 Should be prepared freshly and added in warm condition other wise it will become solid.
 Method of preparation
 The gelatin is dispersed in cold water and allowed to stand until hydrated. The
hydrated mass is warmed in water bath to dissolve.
 Cellulosic solutions
 HPMC (Hydroxy propyl methyl cellulose) Soluble in cold water.
 Method of preparation:
HPMC is dispersed in hot water, under agitation.
 HEC (Hydroxy ethyl cellulose), HPC (Hydroxy propyl cellulose) are other
successful binders.
 PVP (Polyvinylpyrrolidone) is used as an aqueous or alcoholic solution.
Concentration 2% and may vary.

Disintegrants
 A disintegrant is a substance to a mixture of substances, added to
tablet to facilitate its breakup or disintegration after administration
in the GIT.
 The active ingredients must be released from the tablet matrix as
efficiently as possible to allow for its rapid dissolution.
 Disintegrants can be classified chemically as: Starches, clays,
celluloses, alginates, gums and cross-linked polymers.

Cont…
 Starch
 Corn starch, potato starch.
 For their disintegrating effect starches are added to the powder blends in dry state.
 Mode of action:
 Starch has a great affinity for water and swells when moistened, thus facilitating the
rupture of the tablet matrix.
 Others have suggested that the spherical shape of the starch grains increases the porosity of
the tablet, thus promoting capillary action.
 Normally 5% w/w is suggested and for rapid disintegration 10 – 15% w/w may be taken.

Cont..
 Superdisintegrants
 Super disintegrants like Croscarmellose - cross linked cellulose, Crospovidone - cross
linked polyvinyl pyrrolidone and Sodium starch glycolate- cross linked starch
 Mode of action
 Croscarmellose swells 4 to 8 fold in less than 10 seconds
 Crospovidone acts by wicking or capillary action.
 Sodium starch glycolate swells 7 to 12 folds in less than 30 seconds.

Lubricants 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.
 Example: Stearic acid, Stearic acid salt - Stearic acid, Magnesium stearate, Talc, PEG
(Polyethylene glycols), Surfactants.
 Glidants are intended to promote flow of granules or powder material by reducing the
friction between the particles.
 Example: Corn Starch – 5-10% conc., Talc-5% conc., Silica derivative - Colloidal silicas
such as Cab-O- Sil, Syloid, Aerosil in 0.25-3% conc.

Cont…
 Objectives:
 Prevents adhesion of the tablet material to the surface of dies and punches.
 Reduce inter-particular friction, improve the rate of flow of tablet granulation.
 Facilitate ejection of the tablets from the die cavity.

Coloring Agents
 Objectives of using colors
 It makes the tablet more esthetic in appearance
 Colour helps the manufacturer to identify the product during its preparation.
 Colorants are obtained in two forms dyes and lakes.
 Dyes are dissolved in the binding solution prior to the granulating process. However,
during drying their color may migrate to the surface and may produce mottling of the
tablet.
 Color lakes are dyes which are adsorbed onto a hydrous oxide of a heavy metal (like
aluminum) resulting in an insoluble form of the dye.
 So another approach is to adsorb the dye on starch or calcium sulfate from its aqueous
solution; the resultant powder is dried and blended with other ingredients.

Cont…
 Some examples are:
 FD & Cyellow6‐sunsetyellow
 FD & Cyellow5‐Tartrazine
 FD & Cgreen3‐FastGreen
 FD & Cblue1‐BrilliantBlue
 FD & Cblue2‐Indigocarmine
 D & Cred3‐Erythrosine.
 D & Cred22–EosinY

Flavouring agents and sweeteners
 Flavours are usually limited to chewable tablets or other tablets intended to
dissolve in the mouth. Flavor oils are added to tablet granulations in solvents, are
dispersed on clays and other adsorbents or are emulsified in aqueous granulating
agents (i.e. binder).
 The use of sweeteners is primarily limited to chewable tablets. E.g. Sugar
 Mannitol– 72% as sweet as sugar, cooling & mouth filling effect
 Saccharin– Artificial sweetener, 500 times sweeter than sucrose
 Disadvantages (i) it has a bitter after taste and (ii) carcinogenic
 Cyclamate– either alone or with saccharin– it is banned
 Aspartame (Searle) – widely replacing saccharin
 Disadvantage – lack of stability in presence of moisture

Tablet manufacturing process
 Various steps involved in tablet manufacturing are:
Pulverizing/ mixing
Granulation
Compression
Coating (if required)

Pulverization / Mixing
 Pulverization / Mixing:
 In this step the different solid / powder ingredients are reduced to
the same particle size since particles of different sizes will segregate
while mixing.
 Various equipments like Cutter mill, Hammer mill, Roller mill and
Fluid energy mill is required to reduce the large lumps.

Granulation
 It is the process in which primary powder particles are made to adhere to form large multi-
particle entities.
 Range of size: 0.2 mm to 4 mm. (0.2 mm to 0.5 mm)
 Objectives:-
 To enhance the flow of powder.
 To produce dust free formulations and produce uniform mixtures.
 To improve compaction characteristics.
 To eliminate poor content uniformity of mix.
 To avoid powder segregation. As Segregation may result in weight variation.

Cont…
 Various granulating methods includes wet and dry granulation.
 Wet Granulation
 Mixing Commonly used blenders are:
(a) Double cone blender
(b) V – blender
(c) Ribbon blender
(d) Planetary mixer

Cont…
 Wet massing:
 Wet granulation forms the granules by binding the powders together with an adhesive.
 Binder solutions can be added in two methods:
Drug + Diluent
Dry binder is added
Blending
Addition of Suitable Solvent
Drug + Diluent
Binder Solution
is added
Method A Method B

Cont…
 Blended in a Sigma - mixer or Planetary mixer till properly wet mass is formed
 Therefore, when
(i) a small quantity of solvent is permissible, method-I is adopted and
(ii) a large quantity of solvent is required method-II is adopted.
 However, method-II will give more cohesiveness than method-I if the amount of binder
remains constant.
 If granulation is over-wetted, the granules will be hard, requiring considerable pressure to
form the tablets, and the resultant tablets may have a mottled appearance.
 If the powder mixture is not wetted sufficiently, the resulting granules will be too soft,
breaking down during lubrication and causing difficulty during compression.

Cont…
 Wet Screening
 Wet screening process involves converting the moist mass into coarse, granular
aggregates by
 passage through a hand screen (in small scale production) or,
 passage through an oscillatory granulator of hammer mill equipped with screen
having large perforations (# 6 – 8 mesh screen).
 Purpose (i) Increase particle contact point (ii) Increase surface area to facilitate
drying.

Cont…
 Drying
 Drying is usually carried out at 600C. Depending on the thermolabile nature of the
drug the temperature can be optimized.
 Drying is required in all wet granulation procedures to remove the solvent, but is
not dried absolutely because it will pose problems later on. Hence, certain amount
of moisture (1 – 4 %) is left within the granules – known as the residual moisture.
 Methods: Drying can be carried out
 Tray dryers – it may take 24 hrs of drying
 Fluid-bed dryer – carry out drying in 30 mins.

Cont…
 Dry Screening
 After drying, the granules are make monosize by passing through mesh screen.
 Lubrication of granules:
 After dry granulation, the lubricant is added as a fine powder. It usually, is screened onto the
granulation through 60 or 100 mesh nylon cloth to eliminate small lumps as well as increase
the covering capacity of the lubricant.
 The lubricant is blended very gently using tumbling action to maintain the uniform granule
size.
 Too much fine powder is not desirable because fine powder may not feed into the die
uniformly causing variation in weight and density.
 Since, the very nature of lubricant produce hydrophobic surface on the particle hence over
blending prevents the inter granule bonding that takes place during compression.

Cont…
 Dry Granulation
 Dry granulation is followed in situations where
(i) the effective dose of a drug is too high for direct compaction and
(ii) if the drug is sensitive to heat, moisture or both, which precludes wet granulation. e.g.
many aspirin and vitamin formulations are prepared for tableting by compression
granulation.
Steps of granulations
Milling → Weighing → Screening → Blending → Slugging →
Granulation → (Dry) → Lubrication Compaction.

Cont…
 Slugging
 Slug may described as poorly formed tablets or, may be described as compacted
mass of
 powdered material.
 Purpose: To impart cohesiveness to the ingredients, so as to form tablets of desired
properties.
 Method: It is done either by (i) high capacity heavy duty tablet press
(ii) Chilsonator roller compactor.

Advantages of dry granulation over wet granulation
 No application of moisture (required in wet granulation) and heat (for drying). So the drugs
susceptible to either moisture or heat or both can be made by dry granulation. e.g. calcium
lactate cannot be used by wet granulation. (Aspirin, Vitamin C).
 Dry granulation involves less steps and hence less time is required than that of wet
granulation.
 Less steps requires less working space and energy.

Direct compaction / compression
 Milling →Weighing → Sieving → Blending → Compression
 Advantages: (i) It is much more quicker than any of the previous process
(ii) Minimum number of steps are required.
 Modified diluents, binders etc. are available in the market which assure spherical shape of the granules
to modify flow property. However, they are not used extensively.
 If active medicament is less in amount then there will be no problem but in case of high dose large
amount of active ingredient is to be replaced by specially treated vehicles to improve flow property or
compressibility.
 These specially treated materials are costly.

Cont…
 Head- Contain upper punches, dies, lower punches.
 Body- Contain operating machineries.
 Hopper- Holding feeding granules.
 Dies- Define size, shape of tablet.
 Punches – For compression with in dies.
 Cam tracks – Guiding the movement of punches.
 Feed frame- Guiding the granules from hopper to dies.
 Upper turret- Holds the upper punches.
 Lower turret- Hold the lower punches.
 Die table- Contain the dies.

Cont…
 The tablet compression process starts from here. It is at this point that you’ll put all powder
you intend to compress into tablets.
 Tablet press hoppers come in a wide range of shapes and designs. Whatever the shape, it
should be such that the material can flow seamlessly into the tablet compression chamber.
 Again, since it is one section that is in direct contact with the material, it is made of
stainless steel.
 Depending on the design of a tablet press machine, you can fill the powder manually or
using other automated systems.

Cont…
 Hoppers may feature optimal flow angles to facilitate flow, especially where it is nearly
impossible to adjust formulation.
 Some hoppers may feature vibratory rods. This is done carefully to enhance product flow
and to prevent possible product separation.

Punches
 This is yet another critical part of the tablet compression machine parts. Normally, you can
choose from simple to complex shapes of tablet press punches.
 The design and shape of a press punch tool design have a direct impact on the tablet
quality.
 Under normal circumstances, these tablet compression parts are subjected to abrasive
environments and exposed to extremely high pressure.
 Therefore, they require high quality material and if possible with a special coating to
prevent sticking or wear.

Cont…
 To produce the desired tablets, punches move within the die, thereby compressing powder into
the desired tablets.
 In any tablet press machine, we have:
 Upper punch system
 Like the name suggests, the tablet press upper punches are on the upper section of the rotary
system. They move vertically, in and out of the die bore as you can see in the animation above.
 Lower punch system
 The lower punches are on the lower section of the rotary system of the tablet press machine.
During the tablet compression process, the lower punches remain within the die bore throughout
the entire cycle.

Dies
 It is in the die cavity that the powder is compressed into desired tablets of definite
thickness and size.

Cont…
 It is the die cavity that determines both the thickness and size of a tablet. Like the punches,
a die system should have the following key features:
 Clean impression on every punch
 Prevent chipping or damaging of tablets
 Feature anti-corrosion protection
 Have non-stick treatment
 Other critical features we consider whenever we are machining a tablet press die system
include:
 Tapering angle; this is a critical aspect since it allows excess air to escape, while minimizing the
tablet ejection force and frictional heat.

Cont...
 The rotating turrets have holes that host the die system of a tablet making machine. They
are precisely machined to the required rotational tolerances and dimensions.
 It is the tablet press machine turret that determines the number of stations. This helps to
determine the production capacity of the machine for every complete rotation of the turret.

Compression Rollers
 The idea here, is to ensure only powder is compressed to the desired shape and size.
However, at times you may find air within the powder particles.
 To achieve this, tablet compression machines feature a series of rollers that exert a
sufficient amount of force to compress the powder. That is, they expel air first before the
compression process begins.

Cont..
 Most machines have two sets of rollers:
 Pre-compression rollers
 These are the very first rollers in rotary tablet press. Basically, these rollers apply a small
amount of force on the upper and lower punches.
 This gives the initial compression force. The aim of this process is to remove air that could
be in the die or powder particles.
 Any air within the die cavity or powder particles will obviously result in low quality tables.
This process is necessary for the reason that, any powder in the machine’s hopper may
have air between its particles.
 Main compression rollers
 Main compression rollers exert a predetermined amount of force (final compression force)
for the formation of tablets. The compression force at this stage is higher than the pre-
compression force.
 It is important that the rollers remain stable with no vibration during the entire process.
This is to ensure consistency of the tablets’ thickness and size.

Cont…
 Again, the ejection cam is located just after the main compression rollers. Like the other
cam tracks, ejection cams are also critical aspects of tablet compression machine parts.
 Without them, there is no way you’ll access the already processed tablets.
 Remember, after compression, the tablet is always fixed within the die systems (space
between lower and upper punches).
 The ejection cams steadily and slowly push the bottom punch upwards. At the same time,
the top cams move up and so are the top punches.
 As a result, the fully compressed tablets leave the die cavity, i.e. the compressed tablet
remains just at the top of the die.

Take –off blade and Discharge Chute
 The take –off blades are fitted just above the feeder housing. Their main role is to deflect
the fully compressed tablets into the discharge chute.
 The discharge chute, then directs the tablets to a collection bin.

Cont…
 Tablet defects can be related to one of the below mentioned factor:
 Machine related
 Double impression
 Process
 Capping
 Lamination
 Capping
 Chipping
 Formulation Design
 Sticking
 Picking
 Binding

Capping
 Capping occurs when the top and bottom of the tablet are separated from the tablet body.

Cont…
Sr No Causes Remedies
1 Large amount of fines in
granules
Remove fines through 100-
200 mesh
2 Lower moisture content Moisten granules
3 Insufficient amount of
binder
Increase binder amount
4 Poorly finished dies Polish dies properly
5 Lower punch remains
below the die during
ejection
Make proper setting of
lower punches
6 High speed compression Use optimum speed for
compression

Lamination
 Separation of a tablet into two or more distinct layers.
 It mainly occurs due to air entrapment during compression and subsequent release on
ejection.

Cont…
1 Large amount of fines Remove fines
2 Too dry or very low
moisture content
Moisten granules suitably
3 Not thoroughly dried
granules
Dry granules properly
4 Improper amount of binder Increase amount of binders
5 Improper amount of
lubricant
Increase amount of
lubricant

Chipping
 Breaking of tablet edges, while the tablet leaves the press or during subsequent handling
and coating operations.

Cont…
1 Sticking on punch
faces
or increase lubrication
2 Too dry granules Moisten the granules
or add hygroscopic
substance
3 Too much binding
causes chipping at
bottom
Optimize binding or
use dry binders
4 Damaged punch
edges
Replacement of punch
punch

Cracking
 Small, fine cracks observed on the upper or lower central surface of tablets, or very rarely
on the sidewall are referred to as cracks.
 It is generally due to rapid expansion of tablets, especially when deep concave punches are
used.

Cont…
1 Large size granules Reduce granule size
2 Too dry granules Moisten granules
and add proper
amount of binder
3 Tablets expand Add dry binder
4 Granulation too cold
cold
Compress at room
temperature

Sticking
 Tablet material adhere to the die wall.
 Filming is a slow form of sticking and is largely due to excess moisture in the granulation.

Cont…
1 Granules are not dried
properly
2 Improper lubrication Increase or change
lubricant
3 Too much binder Reduce the amount of
binder or use a different
type of binder
4 Hygroscopic granular
material
Modify granulation and
compress under
controlled humidity
5 Oily or waxy material Modify mixing process.
Add adsorbent

Picking
 Small amount of material from the tablet is sticking to and being removed off from the
tablet-surface by a punch face.
 This problem is more prevalent on the upper punch faces than on the lower ones.

Cont…
Sr NO Causes Remedies
1 Excessive moisture in granules Dry granules properly
2 Too little lubrication Increase lubrication
3 Low melting point substances
,ay soften from heat of
compression and may lead to
picking
Add high melting point
materials like lubricants
4 Too warm granules while
compressing
Compress at RT
5 Too much amount of binder Reduce amount of binder
or change type of binder

Double impression
 Involves only those punches which have monogram or other engraving on them.
 If the upper punch is uncontrolled, it can rotate during the short travel to the final
compression stage and create a double impression.

Introduction
It is the application of a coating composition
to a moving bed of tablets with the
concurrent use of heated air to facilitate
evaporation of the solvent.

Objectives
 Protection of the drug from the surrounding (environment) (air, light and moisture) and
thus improve stability.
 Modifying drug release, as in enteric coating and extended-release formulation.
 Masking unpleasant taste or odour of the drug & batch differences in the appearance of raw
materials
 Appearance: Improving product appearance
 Identification: Facilitating rapid identification by the manufacturer, the pharmacist and the
patient (mostly colored).
 Strength: Increasing the mechanical strength of the product.

Types of tablet coating
 Sugar Coated
 Film Coated
 Compression Coating

Sugar Coating
 The sugar coating comprises of successive application of sucrose-based coating solution to tablet
cores in suitable equipment.
 In principle, in the sugar coating, water evaporates from the syrup leaving a thick sugar layer
around each tablet.
 Sugar coated tablets are shiny and highly colored.
 Steps for sugar-coating process
• Sealing/waterproofing (of the tablet cores)
• Sub coating
• Smoothing
• Coloring
• Polishing
• Printing

Cont…
 Sealing
 Sealing or waterproofing involves application of one or more coats of a waterproofing
substance on to the tablet surface.
 These waterproofing substances may be Alcoholic spray, Shellac or Synthetic polymers
e.g. Cellulose Acetate pthallate (CAP).
 This step involves application of many coats of partially or completely water-insoluble
polymers.
 Sugar-coatings are aqueous layers which allow water to penetrate directly into the tablet
core and thus potentially affecting product stability and possibly causing premature

Cont…
 Sub coating
 Large quantities of sugar-coatings are applied to the tablet core (50- 100 % weight
increase) for rounding off the tablet edge in the subcoating stage.
 Much of this material build-up occurs during this stage and is achieved by adding a bulking
agent such as Calcium carbonate, to the sucrose solution.
 Antiadherents e.g. Talc may be added after partial drying to prevent sticking of the tablets
together.

Cont…
 Smoothing
 The subcoating stage results in tablets with rough surfaces.
 To facilitate the color application (which requires a smooth surface), subcoated tablets are
smoothed out by a thick sucrose syrup coating.
 Coloring
 Color coatings usually consist of thin sucrose syrup containing the requisite coloring
materials. (Water-soluble dyes or water-insoluble pigments may be used).

Cont…
 Polishing
 After the coloring step, the tablet surfaces tend to be
smooth but somewhat dull in appearance.
 To achieve glossy finish, final stage involving
application of waxes (beeswax or carnauba wax) is
employed in polishing pan.
 Printing
 Different tablets could be identified by manufacturer'
logo, product name, dosage strength or other appropriate
code.
 For sugar-coated tablets, such identification could be
only achieved by printing process using special edible
inks.

Cont…
 In the sugar coating, the tablets
are taken in a rotating coating pan
for uniform application of coating
solutions which is gently poured
or sprayed, portion wise onto the
tablets with warm air blown to
hasten drying.
 In the process, the second coat is
given after drying of previous one.

Film Coating
 Film coating provides an alternative means of masking the taste of the medicament and
providing protection against adverse climatic conditions without significantly altering the
tablet weight or size.
 Film coating are used to achieve the modified release of drug delivery by using varying
coating materials depending on the type of release.

Cont…
 Types of Film Coating
 Immediate-release (non-functional) film coating: They do not affect the
biopharmaceutical properties of the tablet. They are readily soluble in water.
 Modified-release (functional) film coating: They allow the drug to be delivered in a
specific manner; i.e. they affect drug release behavior.
 Modified release film coatings are sub-classified into;
 Delayed-release coating (enteric coating): Only soluble in water at pH ≥ 5-6. Intended to
protect the drug from gastric acidic pH (for acid labile drugs). Used for colonic drug
delivery systems.
 Extended-release coating: Mostly water-insoluble. Designed to ensure consistent drug
release manner over a long period of time (6-12 hr) and thus decreasing dosing regimen
and improving patient compliance.

Cont…
 Film coating formulation/ materials are composed of
 Polymer,
 Plasticizer,
 Colorants,
 Solvent (vehicle)
 Polymer:
 A film former capable of producing smooth thin films reproducible under the prescribed
coating conditions films e.g. cellulose, vinyl derivatives, carbomers, methacrylate's etc.

Cont…
 Plasticizer:
 Affords flexibility and elasticity to the coat and thus provide durability. Examples;
Polyethylene glycol (PEG), Polypropylene glycol and coconut oil.
 Colorants:
 Provides an elegant appearance. Ex. Iron oxide pigment, Titanium dioxide and Aluminum
lakes.
 Solvent (vehicle):
 Volatile organic solvents may be used to allow good spreadability of the coat components
over the tablet and allowing rapid evaporation, but they are expensive and show
environmental hazards and solvent residue in the formulation must be investigated (certain
limit). Aqueous vehicles are safer, but they show slower evaporation and may affect drug
stability.

Cont…
 Tablet coating
 The conventional "coating-pan'' and “fluid-bed coating equipment” are both used
for coating.
 Basic procedure involves spraying of the coating liquid (solution or suspension)
onto the rotating tablets (in the coating-pan), or tablets held in suspension by
column of air (in the fluid-bed coating equipment), followed by drying to remove
the solvent, leaving a thin film around each tablet core.

Cont…
 Tablet coating system combines several components:
 a coating pan,
 a spraying system,
 an air handling unit,
 a dust collector, and
 the controls.

Cont…
 The tablet coating pan is used for both film coating as well as sugar coating.
 The coating pan is actually a perforated drum that rotates within a cabinet.
 The cabinet enables to control airflow, air temperature, air pressure, and the coating
application.
 The spraying system consists of several spray guns mounted on a manifold, a solution
pump, a supply tank and mixer, and an air supply. The pump delivers the coating solution
to the guns, where it combines with atomizing air to create a fine mist that is directed at the
bed of tablets in the coating pan. The air handling unit heats and filters the air used to dry
the coating on the tablets.
 Depending on the circumstances, it may include a humidifier or dehumidifier. The dust
collector extracts air from the coating pan and keeps a slightly negative pressure within the
cabinet. The controls enable to modulate the operation of all the components to achieve the
desired results.

Cont…
 Fluidized bed coating

Cont…
 Fluidized Bed Dryers (FBDs) are used in granulation, drying and coating. (studied in
granulation).
 Wurster (1959) first described the application of sugar or film coatings to tablets suspended
in an air stream
 In that equipment the coating solution is introduced into the fluidizing air stream at the
base (or top or tangential) of a tall vertical tube in which tablets circulate as they are
coated.
 Evaporated solvent and air are removed at the top of the chamber. As the tablets circulate
in the air stream they are subjected to considerable abrasive action and for this reason they
are compressed with extra firmness on punches which give a well rounded profile.

Cont…
 Compression coating:

Cont…
 Although less popular, it gained increased interest in the recent years for creating modified-released
products.
 It involves the compaction of granular materials around a preformed tablet core using specially
designed tableting equipment.
 Compression coating is a dry process. Mechanically, it is a complex process, as the tablet may be
tilted when transferred to the second die cavity

Cont…
Tablet defect Causes Remedies
Twinning
Two tablets stick
together;
Most common in
capsule shaped tablets
Coating suspension can
not be evaporated
•Reducing spray rate
•Increasing pan speed
Cracking Small, fine
cracks observed
on the upper,
lower or side surface of
tablets
 Use of higher M. Wt.
polymers or polymeric
blends
 Higher internal stresses in
the film ( more than
tensile strength of the film
)
 Use low molecular
weight polymer
 Adjust the plasticizer
& pigment types and
concentration to minimize
internal stresses

Cont…
Tablet defect Causes Remedy
Blistering
It is local detachment of
film from the substrate
forming a blister (due to
compromised elasticity
or adhesive properties.
 Overheating during
the spraying and
drying process
 Use mild drying
conditions, and
 ensure moderate
temperatures at other
stages of the coating
process
Chipping
occurs when the film
becomes
dented and
chipped (mostly on the
edges of the tablet.)
 Decrease in the
rotation speed in the
machinery during the
coating process.
 Poor polymer or
coating solution
(incorrect amount of
plasticizer is used in
the coating solution).
 Increase the hardness
of the film by
adjusting the
proportion of
plasticizer in the
coating solution
 Selecting a polymer
with a higher
molecular weight.

Cont…
Tablet defects Causes Remedy
Cratering
Volcanic-like crater appears
exposing the tablet surface
 Insufficient drying time
to seal the film or
 Use of a high volume of
coating solution.
 Penetration of the
excess coating solution
into the surface of the
tablet.
 Check the efficiency of
the drying process,
decrease spray
application rate and
optimize drying
conditions
Picking
“part of the film sticks to the
pan resulting to some of the
tablet pieces being detached
from the core.”
 Over wetting of tablets
by the polymer solution,
 Insufficient/rapid drying
 Higher rate of
application of coating
solution
 Increasing the efficiency
of the drying process e.g,
by increasing the air inlet
temperature.
 Decreasing the rate of
applying coating solution
 Increasing the solution
viscosity.

Cont…
Tablet defects Causes Remedies
Pitting
Deformation of the core
of the
tablet without any visible
signs of disruption of the
film coating.
• Increase of the tablet
core
temperature than the
melting point of the
materials used in its
preparation
• Nonuniform
spreading of
film.
Control drying
temperature
Blooming
“the fading or dulling of
a tablet colour after a
prolonged period of
storage at a high
temperature.”
• Changes in the
composition of the
surface film.
• Using too much
plasticizer or using a
plasticizer with a low
molecular weight.
• Decrease the
concentration of the
plasticizer in the
polymer.
• Using high molecular
weight plasticizer

Cont…
Blushing
A haziness or appearance
of white specks (particles
of polymer that has
precipitated in the film)
in the film
• Use of excessively
high coating
temperature.
• Gelation of the
polymer
• Decrease the drying
temperature
• Avoid the use of
sorbitol with polymers
such as hydroxy
propyl cellulose,
hydroxy methyl
cellulose, methyl
cellulose and cellulose
ethers
Mottling
Variation in the color of
tablets within a batch.
• poor mixing,
• uneven spray patterns
of the machinery,
• insufficient coating,
migration of soluble
dyes-plasticizers and
other additives during
drying.
• Use lake dyes (free
from dye migration
problem)
• Aim for even
geometric mixing,
• reformulate with
different plasticizers
and additives and/or
use mild drying
conditions.

Cont…
Infilling
The monogram or bisect
is filled and become
narrow
• Uneven spreading of
coating solution and
film
• high amount and rate
of application of
coating solution
• Add alcohol to the
polymer solution to
improve dispersion,
• Use a spray nozzle
capable of finer
atomization.
Orange Peel
a rough surface like
orange peel
• Rapid drying
• Poor tablet
composition causing
it to become soft.
• too high a spray
pressure combined
with a fast spray rate
• Use mild drying
conditions
• Use additional
solvents to decrease
the viscosity of the
polymer solution so
that spraying rate can
be reduced.

Quality Control Test For Tablets

Definition
In general terms, Quality control refers to a
procedure or a set of steps taken during the
manufacturing of a product to ensure that it meets
requirements and that the product is reproducible .

Quality Control Test
 General appearance: - Size, shape, and thickness: This is important to facilitate packaging
and to decide which tablet compressing machine to use.
 Organoleptic properties: which include color, odor and taste of the tablets.
 Weight uniformity and Content uniformity: The tablet should contain the correct dose of
the drug.
 Disintegration Test:
 Dissolution test: Drug should be released from tablet in a controlled and reproducible way.
 Weight variation, thickness & diameter: The appearance of tablet should be elegant & its
weight, size & appearance should be consistent.
 Hardness & friability: The tablet should show sufficient mechanical strength to withstand
fracture & erosion during manufacture & handling.

Weight variation
 The U.S.P. weight variation test is run by weighing 20 tablets
individually, calculating the average weight, and comparing the
individual tablet weights to the average. The tablets meet the USP
test if “not more than 2 tablets are outside the percentage limit and if
no tablet differs by more than 2 times the percentage limit.”

Content Uniformity
 Weight variation test is applicable when the amount of medicament in the tablet is high.
 In potent drug the medicament is less in amount in comparison to the other excipients.
 The weight variation may meet the pharmacopoeia limitation but this will not ensure the
correct variation of potency. Hence, in this case the weight variation test is followed by
content uniformity test.
 In this test 30 tablets are randomly selected for sample, and at least 10 of them are assayed
individually according to the official assay method.
 9 of the 10 tablets must have potency within 15 % of the labelled drug content. Only 1
tablet may be within 25%.
 If this condition is not met then the tablets remaining from the 30 must be assayed
individually and none may fall outside 15% of the labeled content.

Disintegration test
 The time a tablet takes to disintegrate is
the disintegration time.
 To test the disintegration time one tablet is
placed in each tube, and the basket rack
assembly is positioned in a 1-litre beaker
of water, simulated gastric fluid or
simulated intestinal fluid, at 37oC, such
that the tablet remains 2.5 cm from the
bottom of the beaker.
 A standard motor moves the basket up and
down through a distance of 5 to 6 cm at a
frequency of 28 to 32 cpm (cycles per
minute).

Dissolution Test
 Disintegration test simply identifies the time required for the tablet to break up under the
condition of the test but it does not ensure the drug release in the bulk of the fluid.
 Rate of dissolution is directly related to the efficacy of the drug. Rate of dissolution is a good
index for comparing the bioavailability of two tablet products of the same drug.
 Apparatus-I (Basket)
 In general, a single tablet is placed in a small wire mesh basket and immersed in the dissolution
medium (as specified in the monograph) contained in a 1000 ml flask at 37oC . Generally it is
rotated at 50 rpm unless otherwise specified.
 Apparatus-2 (Paddle)
 The same equipment is used. Instead of basket a paddle is introduced as the stirring element. The
tablet is allowed to sink at the bottom of the flask before stirring.
 Limit: A value of t90% (i.e 90% drug release) within 30 minutes is often considered satisfactory
and is an excellent goal since a common dissolution tolerance in the USP/NF is not less than 75%
dissolved in 45 minutes.

Official Standards as per I.P.
 Uncoated tablet:
 Uniformity of weight and Uniformity of content.
 Disintegration test.
 Enteric coated tablet:
 Dispersible tablet:
 Uniformity of dispersion.
 Soluble tablet:
 Effervescent tablet:
 Disintegration/Dissolution/Dispersion test.

Tablets by Ms. Bansari B. Patel (Assistant Professor)

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