2. Tablet is a solid unit dosage form containing
API and excipients prepared by compression
or molding
3. Tablet
A tablet is a unit dosage form that is a mixture of active substances and
excipients, usually in powder form, pressed or compacted into a solid. The
excipients include fillers, binders, glidants (flow aids) and lubricants to ensure
efficient tabletting; disintegrants to ensure that the tablet breaks up in the
digestive tract; sweeteners or flavours to mask the taste of bad-tasting active
ingredients; and pigments to make uncoated tablets visually attractive.
A coating may be applied to hide the taste of the tablet's components, to make
the tablet smoother and easier to swallow, and to make it more resistant to the
environment, extending its shelf life.
The compressed tablet is the most popular dosage form in use today. About
two-thirds of all prescriptions are dispensed as solid dosage forms, and half of
these are compressed tablets. A tablet can be formulated to deliver an accurate
dosage to a specific site; it is usually taken orally, but can be administered
sublingually, rectally or intravaginally.
Medicinal tablets were originally made in the shape of a disk of whatever color
their components determined, but are now made in many shapes and colors to
help users to distinguish between different medicines that they take. Tablets are
often stamped with symbols, letters, and numbers, which enable them to be
identified. Sizes of tablets to be swallowed range from a few millimeters to
about a centimeter. Some tablets are in the shape of capsules, and are called
"caplets".
4. Advantages
1. They are a unit dose form, and they offer the greatest capabilities of
all oral dosage forms for the greatest dose precision and the least
content variability.
2. Their cost is lower than of all oral dosage forms.
3. They are the lightest and most compact of all oral dosage forms.
4. They are in general the easiest and cheapest to package and ship
of all oral dosage form.
5. Product identification is simplest and cheapest.
6. They may provide the greatest ease of swallowing with the least
tendency for hang up above the stomach, especially when coated.
7. Special release profile can be achieved.
8. They are better suited for large scale production
9. They have the best mechanical, chemical and microbiological
stability of all the oral dosage form.
10.Flexibility in dosage.
5. Disadvantages:
1. Some drugs resist compression, owing to their amorphous nature
or flocculent, low density character.
2. Drugs with poor wetting, slow dissolution, intermediate to large
doses are difficult to formulate.
3. Tablets cannot be used adequately in case of emergency cases.
4. Some drugs may be unsuitable for administration by the oral
route. For example protein drugs such as insulin may be
denatured by stomach acids. Such drugs cannot be made into
tablets
5. Bitter tasting drugs, drugs with objectionable odor, or drugs they
are sensitive to oxygen or moisture then an additional step
(coating) is required which adds up to the cost.
6. Tablet Properties
The objective of the tablet dosage form is to deliver orally the correct
amount of drug in the proper form, at or over the proper time and in the
desired location, and to have its physical and chemical integrity protected
to that point.
A tablet should be
1. An elegant product having its own identity being free from defects
such as chips and cracks, discoloration, contamination.
2. Should have the strength to withstand the rigors of the mechanical
shocks during manufacturing, packaging, shipping and dispensing.
3. Should have chemical and physical stability to maintain its physical
attributes.
On the other hand the tablet
1. Must be able to release the drug in the body at predictable and
reproducible manner.
2. Must have suitable chemical stability over time so as not to allow
alteration of the medicinal agent.
We have to set of parameters one physical attributes and chemical
attributes. We must have the balance between the two sets other wise we
will be either very good physical tablets but no drug release or tablets with
good drug release but poor physical properties.
7. ORAL TABLETS FOR INGESTION. These
tablets are meant to be swallowed intact along
with a sufficient quantity of potable water.
Exception is chewable tablet. Over 90% of the
tablets manufactured today are ingested orally.
This shows that this class of formulation is the
most popular world wide and the major attention
of the researcher is towards this direction.
1. Standard compressed tablets
2. Multiple compressed tablets
I. Compression coated tablet
II. Layered tablet
3. Modified Release tablet
4. Delayed action tablet
5. Targeted tablet
I. Floating tablet
II. Colon targeting tablet
6. Chewable tablet
7. Dispersible tablet
8. Sugar Coated tablets
9. Film Coated Tablets
10. Chocolate Coated tablets
TABLETS USED IN THE ORAL CAVITY. The
tablets under this group are aimed to release
API in oral cavity or to provide local action in this
region. The tablets under this category avoids
first-pass metabolism, decomposition in gastric
environment, nauseated sensations and gives
rapid onset of action. The tablets formulated for
this region are designed to fit in proper region of
oral cavity.
1. Lozenges and troches
2. Sublingual tablet
3. Buccal tablet
4. Dental cones
5. Mouth dissolved tablet
Types of Tablets
8. TABLETS ADMINISTERED BY OTHER ROUTES
These tablets are administered by other route
except for the oral cavity and so the drugs are
avoided from passing through gastro intestinal tract.
These tablets may be inserted into other body
cavities or directly placed below the skin to be
absorbed into systemic circulation from the site of
application.
1. Vaginal tablet
2. Implants
TABLETS USED TO PREPARE SOLUTION The
tablets under this category are required to be
dissolved first in water or other solvents before
administration or application. This solution may be
for ingestion or parenteral application or for topical
use depending upon type of medicament used.
1. Effervescent
tablet
2. Hypodermic
tablet
3. Soluble tablet
TABLETS PREPARED BY MOLDING 1. Tablet Triturates
2. Hypodermic
Tablets
9. Manufacturing
In the tablet-pressing process, it is important that all ingredients be dry,
powdered, and of uniform grain size as much as possible. The main guideline in
manufacture is to ensure that the appropriate amount of active ingredient is
equal in each tablet so ingredients should be well-mixed. Compressed tablets
are exerted to great pressure in order to compact the material. If a sufficiently
homogenous mix of the components cannot be obtained with simple mixing, the
ingredients must be granulated prior to compression to assure an even
distribution of the active compound in the final tablet. Two basic techniques are
used to prepare powders for granulation into a tablet: wet granulation and dry
granulation.
Dry granulation
This process is used when the product needed to be granulated may be
sensitive to moisture and heat. Dry granulation can be conducted on a press
using slugging tooling or on a roller compactor commonly referred to as a . Dry
granulation equipment offers a wide range of pressure and roll types to attain
proper densification. However the process may require repeated compaction
steps to attain the proper granule end point.
Process times are often reduced and equipment requirements are streamlined;
therefore the cost is reduced. However, dry granulation often produces a higher
percentage of fines or noncompacted products, which could compromise the
quality or create yield problems for the tablet. It requires drugs or excipients
with cohesive properties.
10. Wet granulation
Wet granulation is a process of using a liquid binder or adhesive to the power mixture.
The amount of liquid can be properly managed, and overwetting will cause the
granules to be too hard and underwetting will cause the granules to be too soft and
friable. Aqueous solutions have the advantage of being safer to deal with than
solvents.
Procedure of Wet Granulation
1.Weighing: the active ingredient, filler, disintegration agents, are weighed.
2.Screening: to remove any lumps or foreign matter.
3.Blending: the active ingredient, filler, disintegration agents, are mixed.
4.Wetting: The wet granulate is prepared by adding the liquid binder/adhesive.
Examples of binders/adhesives include aqueous preparations of cornstarch, natural
gums such as acacia, cellulose derivatives such as methyl cellulose, CMC, and
povidone. Ingredients are placed within a granulator which helps ensure correct
density of the composition.
5.Screening: passing the damp mass through screen to convert into pellets or
granules
6.Drying: Drying the granulation in appropriate dryers (FBD, Tray Dryer etc).
7.Dry screening: After the granules are dried to require moisture content, these are
passed through a screen of smaller size than the one used for the wet mass to
select granules of uniform size to allow even fill in the die cavity.
8.Lubrication: A dry lubricant, antiadherent and glidant are added to the granules
either by dusting over the spread-out granules or by blending with the granules. Its
reduces friction between the tablet and the walls of the die cavity. Antiadherent
reduces sticking of the tablet to the die and punch.
9.Tabletting: Last step in which the tablet is fed into the die cavity and then
compressed between a lower and an upper punch.
11. Wet granulation Dry granulation Direct compression
Milling and mixing of
drugs and excipients
Milling and mixing of
drugs and excipients
Milling and mixing of
drugs and excipients
Preparation of binder solution Compression into slugs or
roll compaction
Compression of
tablets
Wet massing by addition of binder
solution or granulating solvent
Milling and screening of
slugs and compacted
powder
Screening of wet mass Mixing with lubricant and
disintegrant
Drying of the wet granules Compression of tablets
Screening of the dry granules
Blending with lubricants and
disintegrant to produce ‘‘running
powder’’
Compression of tablets
Typical unit operations involved in wet granulation, dry granulation, and direct
compression
12. Excipients
In addition to the active ingredients, the tablets will also contain a range
of substances called excipients. The role of excipients is essential in
ensuring that the manufacturing process is successful and that the quality
of the resultant formulation can be guaranteed. The appropriate selection of
excipients and their relative concentrations in the formulation is critical in
development of a successful product. Although they are often categorized
as inert, preformulation studies can determine the influence of excipients
on stability, bioavailability, and processability.
Excipients for Tablets
13. Criteria for excipients:
• They must be non toxic
• They must be acceptable to regulatory agencies in all countries
where the product is to be marketed.
• They must be commercially available in all grades in all countries
where the product is to be manufactured.
• Cost must be acceptably low.
• they must not be contraindicated by themselves or because of any
component thereof.
• They must be physiologically inert.
• They must be physically and chemically stable by themselves and in
combination with drug and other excipient in the formulation.
• They must be free from any unacceptable microbial load.
• They must be color compatible.
• Preferably they may be approved as food additive (especially for
nutrients formulation)
• They must not interfere with the bioavailability of the drug.
14. Diluents
An inert substance is frequently added to increase the bulk of a tablet for processing
and handling. The lower weight limit for formulation of a tablet is usually 80 mg.
Ideally, diluents should be chemically inert, nonhygroscopic, and hydrophilic. Having
an acceptable taste is important for oral formulations, and cost is always a
significant factor in excipient selection.
1. Lactose: It is a common diluent and it fulfils most of these criteria but is
unsuitable for those who are lactose intolerant. Various lactose grades are
commercially available i.e. mesh 60 -80 (Coarse) and 80 - 100(regular) which
have different physical properties such as particle size distribution and flow
characteristics. Lactose is available as hydrous and anhydrous. Lactose hydrous
not anhydrous under go Mailard reaction in the presence of amine drug specially
with Mg stearate as lubricant. It is also available in spray dried from for direct
compression.
2. Starch: It may be obtained from corn, potato and wheat. For direct compression
Sta-Rx 1500 (Pregelatinized starch) is available. Two hydrolyzed starches
Emdex and Celutab which are combination of dextrose and maltose, these are
free flowing and also can be used in place of mannitol in chewable tablets
because of their sweetness and smooth feeling in mouth.
15. 3. Microcrystalline cellulose (Avicel) is purified partially depolymerized
cellulose, prepared by treating α - cellulose with mineral acids. In
addition to being used as a filler, it is also used as dry binder and
disintegrant in tablet formulations. There are three commercial grades
available PH 101, 102 and 200. these are unique in nature as the
produce cohesive compact the material also act as disintegrant.
4. Dibasic calcium phosphate (both anhydrous and dihydrate forms) is the
most common inorganic salt used as a filler and binder for direct
compression. It is particularly useful in vitamin products as a source of
both calcium and phosphorous. Milled material is typically used in wet
granulated or roller compacted formulations. The coarse grade material
is typically used in direct compression formulations. It is insoluble in
water, but its surface is alkaline and it is therefore incompatible with
drugs sensitive to alkaline pH. Additionally, it may interfere with the
absorption of tetracyclines.
5. Dextrose is available in two forms hydrous and anhydrous. It is some
times used to replace some quantity of spray dried lactose to reduce the
tendency of darkening.
6. Mannitol is the most expensive sugar used as tablet excipient but
because of its negative heat of solution, slow solubility and pleasant
feeling in the mouth make it excellent diluent for chewable tablets
especially for multivitamins.
16. 7. Sorbitol is an optical isomer of mannitol and is some times combined in
formulation with mannitol to reduce cost but it is hygroscopic above 65 %
RH.
Binders
Binders (or adhesives) are added to formulations to promote
cohesiveness within powders, thereby ensuring that the tablet remains
intact after compression as well as improving the flow by forming
granules. A binder should impart adequate cohesion without retarding
disintegration or dissolution. Binders can be added either as a solution or
as a dry powder. Binders added as dry powders are mixed with other
powders prior to agglomeration, dissolving in water or solvent added
during granulation, or added prior to compaction. Solution binders can be
sprayed, poured, or mixed with the powder blend for agglomeration and
are generally more effective.
1. Acacia and Tragacanth: these are used in solution from 10 – 25%. These
natural gum s have the disadvantage being variable in their compositions
as their origin is natural. They are also sensitive to microbial
contamination their wet masses should be quickly dried.
17. 2. Gelatin is a natural protein and is more consistent in composition as
compare to other it form clear solution and give good hard tablets.
3. Starch Paste is the most common binder used for wet granulation.. It
is prepared by dispersing it in cold water and then adding to the
boiling water , heating results in hydrolysis of starch to glucose and
dextrin, starch paste is translucent and forms cohesive tablets that
readily disintegrate.
4. Liquid glucose is 50% aqueous solution and commonly used binder.
5. Sugar is used as 50 and 74 % aqueous solution. They are low cost
binders but are prone to microbial growth.
6. Sodium alginate, Cellulose derivatives (MC, HPMC, EC, HPC, HEC,
SCMC) are used both in dry and wet form.
7. Polyvinyl pyrrolidone (PVP) a synthetic polymer is also utilized.
18. Disintegrants
Disintegrants are added to a formulation to overcome the cohesive strength
imparted during compression, thus facilitating break up of the formulation in
the body and increasing the surface area for dissolution. On contact,
disintegrants can draw water into the tablet, swelling and forcing the tablet
apart.
Starch, a traditional and still widely used disintegrant, will swell when wet.
The normal range is 5% w/w but 15 – 20% w/w can be used if a rapid
disintegration is required.
Surfactants can also act as disintegrants promoting wetting of the
formulation e.g. sodium lauryl sulfate.
Some disintegrant produce carbon dioxide on contact with water e.g.
sodium bicarbonate and a weak acid such as citric acid or tartaric acid .
Compared to the more traditional starch, newer disintegrants
Superdisintegrants are effective at much lower levels. Superdisintegrants are
so called because of the relatively low levels required (2 – 4% w/w).
There are three groups,
1.Modified starches (Xplotab, Primogel)
2.Modified cellulose (Ac-Di-Sol)
3.Cross - linked povidone.
19. Sodium starch glycollate (Primojel, Explotab) is made by cross - linking
potato starch and can swell up to 12 - fold in less than 30 seconds.
Crospovidone is completely insoluble in water, although it rapidly disperses
and swells in water, but does not gel even after prolonged exposure. It
rapidly exhibits high capillary activity and pronounced hydration capacity
with little tendency to form gels and has a greater surface area – volume
ratio compared to other disintegrants.
Micronized versions are available to improve uniformity of mix.
Croscarmellose sodium, a cross linked polymer of carboxymethyl cellulose
sodium is also insoluble in water, it rapidly swells to 4 – 8 times its original
volume on contact with water.
20. Lubricants
Lubricants can reduce friction between the tablet and the die wall during
compression and ejection.
The hydrophobic stearic acid and stearic acid salts, primarily magnesium
stearate are the most widely used and are included at concentrations less
than 1% w/w inorder to minimize any deleterious effects on disintegration or
dissolution. They should be added after the disintegrant to avoid coating it
and preferably at the final stage prior to compression to ensure mixing time
is kept to a minimum. Hydrophilic lubricants such as polyethylene glycols
(PEGs) and lauryl sulfates can be used.
Glidants and Antiadherents
Like lubricants, glidants are fine powders and may be required for tablet
compression at high production speeds to improve the flow properties of the
material into the die or during initial compression stages. They are added in
the dry state immediately prior to compression and, by virtue of their low
adhesive potential, reduce the friction between particles. Colloidal silica
(0.25-3%), starches (5-10%) and talc (5%). Antiadherents can also be
added to a formulation that is especially prone to sticking to the die surface
(or picking). Water insoluble lubricants such as magnesium stearate can be
used as antiadherents,
21. Colors:
Use of colors have three purposes;
• Disguising of Off colour drugs
• Product identification
• Production of more elegant product
The colors used in tablet formulation are of two categories FD&C and D&C.
These are used as dyes or lake. Dyes are soluble and used in solution form
while lakes are colors when dye is deposited over silica or alumina and used in
powder form. The most common and stable colours are iron oxide red and
yellow.
Flavour:
These are usually limited to chewable tablets water soluble flavours are not
commonly used because of their instability, oils are commonly employed.
Sweeteners:
Sweeteners are also limited to chewable tablets or tablets for buccal cavity.
Mannitol is commonly used which is about 72% as sweet as sugar. Saccharin
is artificial sweetener which is about 500 times more sweeter than sucrose, it
has disadvantage that it has bitter after taste and reported as carcinogenic.
Aspartame is also artificial sweetener with a disadvantage of being instable in
the presence of moisture.