TABLETS

• Pharmaceutical oral dosage form or solid unit dosage form.

• Tablets may be defined as the solid unit dosage form of medicament or
medicaments with suitable excipients.
• It comprises a mixture of active substances and excipients, in powder form,
pressed or compacted from a powder into a solid dose.

Types:

Tablets are classified by their route of administration/function.

I) Tablets ingested orally

1. Standard compressed tablets

2. Multiple compressed tablets
3. Delayed action and enteric coated tablets
4. Film coated tablets
5. Sugar coated tablets

II) Tablets used in the oral cavity

1. Buccal and sublingual tablets

2. Troches and lozenges
3. Dental cones
III) Tablets administered by other routes

1. Implantation tablets
2. Vaginal tablets

IV) Tablets used to prepare solution

1. Effervescent tablets
2. Dispensing tablets
3. Hypodermic tablets
4. Tablet triturates

Standard coated tablets

• Usually rapidly disintegrate and releases drug.

• Drugs intended for local effects in GIT
• Their effect occurs by disintegration of tablet --> formation of small
fragments--> dissolution of drug in fragments --> then absorption of drug
through membrane --> distribution in the body.
• Dissolution--> surface related phenomenon
As particle size decreases--> surface area increases.
As surface area increases--> rate of dissolution increases.
Multiple compressed tablets
• Layered and compression coated tablets.
• Their types are
i) Two or three layered tablets
ii) A tablet within a tablet
 iii) A tablet within a tablet within a tablet.

Reasons for preparation of such tablets:

1. To separate physically and/or chemically incompatible ingredients.

2. To produce repeat action or prolonged action product.
3. In multiple compressed tablets, one layer provides initial dose by rapid
disintegration and other layer then slowly disintegrates to release drug in
intestinal environment.

Limitation:
• Unpredictable and uncontrolled release of drugs is achieved.
• Action of product depends on gastric emptying.

Delayed action and enteric coated tablets

• Delayed action tablets are intended to release drug after some time (a delay)
or after the tablet passes certain passage in GIT.
Example: Enteric coated tablets. These are intended to release the drug in
intestinal environment.
Purpose:
1) To protect acid labile drugs from degradation
2) To exert local action in the intestine e.g. in intestinal worm or parasite infection.

Sugar coated tablets

• Sugar coating (sugar syrup coating) is performed to mask the unpleasant

taste and odor of the drug
 • Smaller tablet is compressed and sealing is done by coating it with enteric
coating or cellulose materials.
• Then it is coated with multiple layers of syrup and finally polished.

Film coated tablets

• A solution of polymer(s) in an organic solvent(s) is sprayed over tablets to

form a thin film on the tablets.
• Film coating provides mechanical strength to tablets, masks the unpleasant
odor and taste.

Chewable tablets

• These are intended to be chewed in mouth prior to swallowing.

• E.g. antacids. Antacids are high dose & bigger tablets which cannot be
swallowed easily. In this case preparation of chewable tablets is feasible.
• Bitter tasting drugs cannot be formulated as chewable tablets.

Effervescent Tablets

• Effervescent tablets are uncoated tablets contain organic acids ( tartaric or

citric acid) and sodium bicarbonate in addition to the API.
• They react rapidly in the presence of water by releasing carbon dioxide
which acts as a disintegrator to produce either a drug suspension or an
aqueous solution.
• These tablets are prepared by compressing granular effervescent salts
(organic acid and bicarbonate) with the medicinal substances.
Buccal and sublingual tablets (systemic effect)

• These tablets are intended to be held in the mouth where they release
drug which is absorbed through oral mucosa.
• Buccal tablets--> held between cheek & gums or in cheek pouch.
• Sublingual tablets--> held beneath the tongue.
The absorption from oral mucosa releases drug directly into the general
circulation avoiding first pass metabolism.

Advantages:

• Avoids contact with gastric acid thereby avoiding decomposition of

certain drugs. E.g. certain steroids and hormones.
Rapid onset of drug action occurs e.g. vasodilator drugs.
• First pass effect ( hepatic drug metabolism) is avoided.
• These tablets do not disintegrate but slowly dissolve in mouth for the
period of 15 to 30 minutes.

Troches and lozenges (Local effect)

• These tablets are also held in oral cavity but their actions are local in mouth
or throat.
E.g. Formulation for sore throat or coughing treatment.
• These contain local anesthetics, various antiseptics & antibacterial agents,
demulcents, astringents & antitussives.
• Lozenges are commonly known as cough drops.
 IDEAL REQUIREMENT:

• A tablet must be strong and hard to withstand mechanical shock during

manufacturing, packing, shipping, dispensing and use.

• The drug content of the tablet must be bioavailable, the tablet must be able to
release its content in a predictable and reproducible manner.

• The tablet must be chemically and physically stable to maintain its chemical and
physical attributes during manufacture, storage, and use.

• The tablet should have elegant product identity which is free from any tablet
defect.

• Tablets must be uniform in weight and in drug content.

GRANULATION METHODS

• Granulation is a unit operation in which small powder particles are gathered

together to form agglomerates called granules. To achieve cohesion between
the powders.
• It is necessary to include adhesive substances called binders or granulating
agents within the formulation.
• Powder mixing, in conjunction with the cohesive properties of the binder,
enables the formation of granules which when compressed using tablet
press forms tablets with the desired properties.

Reasons for granulation:

1. To enhance the flow properties of powder mix.

2. To prevent segregation of powder components during tabletting or storage.

3. To reduce the incidence of dust production.

4. To reduce cross-contamination and hazard associated with the generation of toxic

dust that may arise during manufacturing processes.

5. To improve the compression characteristics of drug substances.

6. To improve the appearance of the final product.

Wet granulation

• Wet granulation method is a process of size enlargement in which fine

powder particles are agglomerated or brought together into larger, strong and
relatively permanent structure called granules using a suitable non-toxic
granulating fluid such as water, isopropanol or ethanol (or mixtures thereof).
• The granulating fluid can be used alone or as a solvent containing binder or
granulating agent.
• The choice of the granulating fluid depends on the properties of the
materials to be granulated.
• Powder mixing, in conjunction with the cohesive properties of the
granulating agent, enables the formation of granules.
• The characteristics and performance of the final product depends on the
powder particles interact with each other to form aggregates (granules).

1. Milling of drugs and excipients.

2. Mixing of drugs and excipients (excluding the lubricant).

3. Preparation of binder dispersion.

4. Mixing of binder solution with powder to form a coarse mass.

5. Coarse sieving

6. Drying of moist granules.

7. Sieving of the dried granules and mixing with disintegrant and lubricant.

8. Compression into tablets.

Steps in wet granulation method of tablet production

 Step 1: Weighing and mixing of formulation ingredients (excluding the lubricant).

Step 2: Preparing the damp mass

Step 3: Wet screening/ Screening the dampened powder into pellets or granules

• The wet massed powder blend is screened using 6- to 12- mesh screen to
prepare wet granules.
• This may be done by hand or with suitable equipment that prepares the
granules by extrusion through perforations in the apparatus. The granules
formed are spread evenly on trays and dried in an oven.

Step 5: Sizing the granulation by dry screening

• The dried granules are passed through a screen of smaller size than that used
to prepare the moist granules. The size of the final granules is dependent on
the size of the punches (and hence the final tablet size). Screens of 14- to 20-
mesh size are generally used for this purpose.

Step 6: Lubrication of granules

Step 7: Compression of granules into tablets

Recent advances in wet granulation technology

1. Steam granulation

2. Moisture-Activated Dry Granulation/ moist granulation

3. Freeze granulation

4. Thermal adhesion granulation

5. Melt granulation/ thermoplastic granulation

6. Foam granulation and

7. Reverse wet granulation/ reverse-phase wet granulation

Manufacture of Tablets by Dry granulation method

• Dry granulation also referred to as precompression or double compression is

a size enlargement process designed to improve the flow and compression
characteristics of powders that would otherwise be unsuitable for
compression.
• The process involves compaction of powder particles into large pieces or
compacts which are subsequently broken down into granules to produce
granules that can be further processed into dosage forms.
• Dry granulation is typically used in the manufacture of tablets if the
formulation ingredients are too fluffy or too susceptible to flowability
problems for direct compression to be a viable processing option and/or too
susceptible to degradation from heat and/or moisture for wet granulation to
be a viable processing option for densification.
• The process is sometimes chosen as an alternative to wet granulation when
direct compression is not feasible not because wet granulation is not feasible
but because the manufacturer is more experienced with dry granulation or to
reduce processing time and/or equipment requirements to reduce costs.
• The manufacture of tablets by dry granulation method eliminates a number
of unit operations but still include milling or micronization of drugs,
weighing, mixing, slugging, dry screening, lubrication, and compression of
granules into tablets.
• For successful manufacture of tablets using dry granulation, either the active
ingredient or the diluent must have sufficient inherent binding or cohesive
properties.
Methods of dry granulation

Either by slugging technique or roller compaction.

Slugging technique

• This process involves compression of primary powder particles into large

flat tablets or pallets using a tablet press or, more usually, a large heavy-duty
rotary press.
• The resultant compact is then milled using a hammer mill or
other conventional milling equipment. The milled slugs are passed through a
screen of desired mesh for sizing. Lubricant is added in the usual manner,
and the granules compressed into tablets.
• Slugging results in considerable dust production which poses a problem for
good containment and reduction of cross-contamination. Other main
shortcomings of slugging include batch processing, low throughput (30–50
kg/hr), poor process control, frequent maintenance changeovers and poor
economy of scale.
• The method is being replaced by the more modern, and better, roller
compaction process.

Roller compaction

• Roller compaction (also referred to as ribbon blending) is a relatively

simple, more efficient and inexpensive form of dry granulation.
• It is a process where formulation ingredients are continuously passed
between two counter-rotating rollers where it is densified and consolidated
into a sheet of solid mass.
 • Depending on the type of rollers used, the feed material may be compacted
into dense ribbon-like materials known as flakes (smooth rolls) or dense
briquettes (almond or stick-shaped) if the rollers have grooved or etched
surfaces. The compacted materials are further milled, sized, lubricated and
compressed into tablets.
• Roller compaction offers distinct advantages over wet granulation,
particularly for moisture-, solvent-, or heat sensitive formulation ingredients.
In the pharmaceutical industry, it is an attractive granulation alternative as it
offers considerable cost savings due of its high production throughput (up to
100,000 kg/hr), shorter cycle times and fewer processing steps. Moreover,
elimination of a drying step reduces production and development time as
well as ease of scale-up.

Excipients used in manufacture of tablets by dry granulation method

• Diluent/filler, e.g., Microcrystalline cellulose (MCC), anhydrous lactose or lactose
monohydrate, dibasic calcium phosphate, starch etc.

• Disintegrants, e.g., croscarmellose sodium, sodium starch glycolate, pregelatinized

starch 1500, crospovidone, starch, MCC, etc.

• Lubricants, e.g., stearates (magnesium stearate, stearic acid), glyceryl fatty acid
esters (glyceryl behenate, glyceryl palmitostearate), Polyethylene glycol (PEG),
polyoxyethylene stearates, sodium lauryl sulphate.

• Glidants, e.g.: talc, colloidal silicon dioxide.

• Miscellaneous excipients such as colourants, flavourant, sweetening agents, etc.

Steps involved in dry granulation

Weighing formulation ingredients

1.Appropriate quantities of formulation ingredients are dispensed. The excipients

and the active ingredient(s) must be in finely divided form, otherwise, particle size
reduction should be carried out.
2. Mixing of formulation ingredients

• The dispensed formulation ingredients are mixed in a powder mixer until a

uniform powder mix is achieved. It is worth noting that half amount of
lubricant in the formula is added at this stage to enhance powder flow during
slugging and to prevent sticking of compressed powder on the die during
precompression.

3. Compression of mixed powders into slugs

• Here, the mixed ingredients are compressed into flat large tablets or pallets.
This step is called precompression (slugging) and the compacts made in the
process (typically 25 mm diameter by about 10–15 mm thick) are termed
slugs. Compression of mixed powders into slugs can be achieved either by
slugging technique or roller compaction. The pressure used to produce the
slugs is usually less than that used in the final compression.

4. Milling and sieving of slugs

• Following slugging, the next stage in the manufacture of tablets by dry

granulation usually involves breaking of slugs into smaller pieces using a
hammer mill or other conventional milling equipment. The milled slugs are
screened to produce uniform granules.

5. Mixing with disintegrant and lubricant

• After screening, the remaining lubricant and other extragranular excipients

such as disintegrant, glidant etc., are added to the granulation and mixed
gently to achieve a uniform blend.
 6. Compression of granules into tablets

• The mixed granules are compressed into tablets using either single or rotary
tablet press fitted with appropriate punches and dies.

Similar to wet granulation, tablets manufactured by dry granulation method may be

coated if the need arises.

Advantages of dry granulation

As with wet granulation, there are several advantages associated with dry
granulation and they include:

1. Dry granulation requires less equipment and minimum floor space.

2. The process eliminates the addition of moisture and allows dry handling of
moisture sensitive formulation ingredients.

3. The process is suitable for heat sensitive materials since no drying step is involved.

4. Dry granulation is not generally associated with alterations in drug morphology

during formulation process.

5. The process does not require special excipients that is, it makes use of
conventional grades of excipients.

6. Tablets manufactured by dry granulation method have improved disintegration

time because the dry binder used has less adhesive effect thus fast disintegration.

7. The process is easily scaled up from development to production.

8. It improves blending since there is no migration.

 Disadvantages of dry granulation
1. Dry granulation method (roller compaction) require specialized heavy duty
equipment for granulation.

2. The process generates considerable dust which may cause cross contamination.

3. Segregation of components may occur post mixing.

4. There may be issues regarding powder flow.

5. Tablets manufactured by dry granulation tend to be softer than those manufactured

by wet granulation, rendering them more difficult to process using post-tabletting
techniques, e.g. film coating.

Manufacture of Tablets by Direct Compression Method

• The processing of drug with excipients can be achieved without any need of
granulation and related unit operations. By simply mixing in a blender,
formulation ingredients can be processed and compressed
into tablets without any of the ingredients having to be changed. This
procedure is called direct compression and it is used in the manufacture of
tablets when formulation ingredients can flow uniformly into a die cavity.
• The term direct compression was reserved for a small group of granular
chemicals having all the physical characteristics that enable them to be
directly compressed into tablets without an intermediate granulating step. As
such, it was only used for chemicals, such as potassium salts (chlorate,
chloride, bromide, iodide, nitrate, and permanganate), ammonium chloride,
and methenamine.
• The term direct compression (or direct compaction) is used to define the
process by which tablets are compressed directly from powdered active drug
 substance and suitable excipients into a firm compact without employing the
process of granulation.
• The successful application of direct compression technique in tablet
manufacture especially for low and medium dosage range of drugs can be
attributed to the availability of new excipients, modified form of old
excipients, and the invention and utilization of new tablet machinery.

Techniques in direct compression

1. Direct compression technique using induced die feeders

2. Direct compression technique using dry binders and

3. Direct compression technique using direct compression excipients

Direct compression technique using induced die feeders

• This involves the use of a special feeding device which prevents segregation
and enhances the flow of powders from the hopper into the die cavity of a
tablet press.
• The use of induced die feeder also reduces air entrapment, making the fill
powder more dense and amenable to compaction.
• Direct compression technique using induced die feeder is used when
formulation ingredients will compact but will not adequately fill the die
cavity.
Direct compression technique using dry binders

• This technique will affect compression of drugs at relatively low filler to

drug ratio, with little addition of preparatory techniques.
• Materials used as dry binders should possess adequate cohesive or
compressibility properties in order to form satisfactory tablets of acceptable
hardness and friability.
• They should possess adequate flowability and bulk density to ensure the die
cavities are uniformly filled and hence tablets of uniform weight and drug
content would be obtained.
• They should also have high capacity or low binder to drug ratio in order to
make possible the manufacture of suitable sized tablets containing relatively
high doses of drugs.

Examples of dry binders used in the manufacture of tablet by direct compression

method include microcrystalline cellulose, polyethylene glycol 400, polyethylene
glycol 6000 etc.
 Direct compression technique using direct compression excipients

• A direct compression excipient also referred to as direct compressible

excipient or direct compression filler/binders are inert, non-medicinal
substances which may be compacted with no difficulty and which may do so
even when mixed with drug substances.
• Direct compressible excipients should exhibit satisfactory tabletting
characteristics. This is because they determine the overall characteristics of
the tablet, particularly in regard to the fluidity of the component powders.
• Direct compressible excipients can also influence the hardness,
disintegration and dissolution characteristics of the finished tablets.

Excipients used in the manufacture of tablets by direct compression method

• Spray-dried lactose (Lactopress Spray-Dried, Lactopress Spray-Dried 250,
Pharmatose DCL 11, Pharmatose DCL 14).

• Dicalcium phosphate (e.g. Encompress grades)

• Mannitol (granular or spray-dried grades, e.g. Pearlitol)

• Sorbitol

• Microcrystalline cellulose (e.g. Avicel pH-102)

• Disintegrants

Examples of excipients that are commonly used as disintegrants for direct

compression technology include:

• regelatinised starch (e.g. Starch 1500)

• Sodium starch glycolate (e.g. Explotab, Primojel)

• Croscarmellose sodium (e.g. Ac-Di-Sol, Explocel)

• Crospovidone (e.g. Polyplasdone XL, Polyplasdone XL-10, Kollidon CL, Kollidon

CL-M).

d. Lubricants and glidants

The types of lubricants and glidants used in the manufacture of tablets by direct
compression method are similar to those used in other tablet manufacture methods
and include:

• Lubricants (e.g., magnesium stearate, stearic acid, sodium stearyl fumarate)

• Glidants (e.g., talc, colloidal silicon dioxide).

 Advantages of direct compression technology
1. Direct compression method requires fewer processing steps (unit operations) and
less equipment. Therefore, the method is potentially less expensive than other
methods used in tablet manufacture.

2. Tablet manufacture can be carried out without the involvement of moisture and
heat. Hence, product stability is almost guaranteed.

3. Some direct compressible excipients possess inherent disintegration properties e.g.,

microcrystalline cellulose.

4. Tablets produced by direct compression method generally show faster dissolution

times than those prepared by wet granulation. This is because tablets manufactured
by direct compression method disintegrate into primary particle state unlike those
manufactured by wet granulation method which breaks down into granules and
finally into primary particle state.
5. Changes in dissolution profile are less likely to occur in tablets manufactured by
direct compression (if stored for a long time) than in those prepared by wet
granulation.

6. Because direct compression excipients have a relatively high binding capacity, the
pressure required to manufacture the desired hardness is, in general, less with
direct compression vehicles than with conventional granulations, resulting in both
higher production rates and longer machine life.

7. Lubrication is performed in the same vessel as powder mixing, thereby reducing

both transfer losses and contamination of equipment.

Limitations of direct compression technology

1. High-dose drugs may present problems with direct compression if it is not easily
compressible by itself.
2. The choice of excipients used in the manufacture of tablets by direct compression
technology is highly restricted since most materials do not have inherent binding
properties.

3. Low-dose drugs may not be uniformly blended.

4. Direct compression excipients are often more expensive than other tablet
excipients used in wet granulation or slugging.

5. A vast majority of drug substances are rarely so easy to tablet by direct

compression. Thus, in choosing a vehicle, it is necessary to consider the dilution
potential of the major filler-binder (i.e., the proportion of the drug substance that
can be satisfactorily compressed into tablets with a direct compressible excipient).
6. Direct compression blends are subject to unblending/ segregation in post-blending
handling steps. This arises from lack of moisture in the blends (which may give
rise to static charges leading to unblending) or variations in particle size or density
of formulation ingredients. This problem can be solved by applying the concept of
ordered blending and/or use of excipients of narrow particle size ranges.

7. In some instances, direct compression excipients may interact with the drug
substance. A good example of such reaction is that which occurs between amine
compounds and spray-dried lactose and this results in a yellow discolouration of
the tablets.

8. Tablet defects such as sticking, capping and lamination are usually pronounced in
tablets manufactured by direct compression method.

Evaluation of tablets

Unofficial tests:
1. Appearance
2. Size and shape
3. Organoleptic properties (color, odor, taste)
4. Hardness
5. Friability

Official tests:
1. Drug content
2. Weight variation
3. Disintegration
4. Dissolution