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ADVANT AGES
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The absorption of therapeutic agents from tablets is dependent on physiological factors, e.g. gastric emptying rate
and shows interpatient variation.
May be problematic for children and elders due to difficulties in swallowing.
Advantages
Unit dosage forms with accurate, stable dose and great precision and least variability.
Most stable with respect to physical, chemical and microbiological attributes.
Cheapest oral dosage form, easy to handle, use and carry out with attractive and elegant
appearance.
Cheap, easy to swallow and production does not require and additional processing steps.
Provide protection of medicaments from atmospheric conditions like air, moisture and light, etc.
Provide prolonged stability to medicaments.
Low manufacturing cost as compare to other solid dosage forms and large scale production is
possible.
Administration of minute dose of drug in accurate amount.
Unpleasant taste can be masked by sugar coating.
Easy to divide into halves and quarters whenever fraction dose is required.
Formulate as a special release products such as enteric or delayed release products.
Packing and production is cheap and does not require more space for storage.
Disadvantages
Drug which are amorphous and low density character are difficult to compress into tablet.
Hygroscopic drugs are not suitable for compressed tablets.
Drugs with low or poor water solubility, sloe dissolution, high absorbance in GI tract may be
difficult to formulate.
Sensitive to oxygen drugs may require special coating.
Cost of production may be increase because of coating and encapsulation to remove bitter and
unpleasant taSome tablet may cause problem in bioavailability.
Difficult to formulate liquid in tablet and swallowing is difficult especially for children and ill
patients.
Delayed action or Enteric coated tablets: These types of tablets contain a coating which resist
dissolution of tablets in Gastro Intestinal Track (GIT) and disintegrate in intestinal fluids thus
rendering delayed release features. Enteric coating is generally apply when drug substance is
unstable in gastric fluid and may destroyed or may cause irritation in gastric mucosa or to extent
absorption of drug from intestine. Normally coating materials mixed with acid and acid
functionality or modified natural polymers. Most commonly used coating polymers are:
Cellulose acetate phthalate (CAP), polyvinyl acetate phthalate (PVAP) and hydroxyl propyl
methyl cellulose phthalate.
Sugar coated tablet: Compressed tablets may be coated with coloured or uncoloured sugar
coating and the coater is water soluble and dissolve quickly after swallowing. Sugar coat protects
drug from environment, remove bitter taste and odour, enhance the appearance of tablet and
permit identifying information. Sugar coating has some disadvantages like increase coat of
production, require expertise for coating, increase size and weight.
Film coated tablets: Tablets are compressed with a thin layer of polymer which forms a skin like
film over tablet. The film is usually coloured, more durable and less bulky. The coating is
designed to rupture and expose of tablet at desired location within GIT. Most commonly used
polymers are Hydroxy propyl cellulose, Hydroxy ethyl and propyl methyl cellulose.
Chewable tablet: These types of tablets have smooth surface, creamy base and usually flavoured
and coloured mannitol, rapid disintegration which allow dissolving quickly in mouth. These
types mostly useful for administration of large dose to children and adults.
local effects with slow dissolution. They contain anti bacterial effect and also called vaginal
inserts.
Implantation tablet: Implantation tablets are injected under the skin by giving a small surgical cut
into the skin. A special injector a hallow needle and plunger may require for administration.
Purpose of these tablets is to prolong drug effect from month to year. These tablets are implanted
intramuscularly or subcutaneous so they must be sterile and packed in sterile container.
[Pharmaceutics - I, P.V. KASTURE, S.R. PARAKH, S.A. HASAN, S.B. GOKHALE, June 2008,
pp-14-7,21]
Tablet Excipients:
Excipients are substance other that active ingredient in formulation of tablet. The roles of
excipients are to ensure tabletting operation satisfactory and ensure that tablets of specified
quality are prepared. Depend on intended use; they are subcategorised in different groups.
However excipients affect properties of tablets.
Diluents or filler
A small amount of powder requires forming suitable size tablet for easy handling. Normally
tablet weigh 50mg so some amount of bulk drug requires to incorporation in formulation of
tablet which enhance size of tablet. These powders known as diluents or fillers. The ideal dilute
should have following properties- cheap, chemically inert, acceptable taste, good compactability
and dilution capacity, biocompatible, good biopharmaceutical properties and non hygroscopic.
A single substance cannot fulfil all these requirements so different substance have gained use as
diluents mainly carbohydrates and inorganic salts sometimes. The most common diluent is
lactose because it possess a sires of good properties like dissolves readily in water, has a pleasant
taste, non hygroscopic is fairly non reactive and shows good compact ability. Its main limitation
is that some people have intolerance to lactose. Basically lactose exists in two forms crystalline
and amorphous. Other sugar and sugar alcohols such as glucose, sucrose, and mannitol have
been used as alternative fillers, mostly in chewable tablets or lozenges because of their pleasant
taste. Other important example of the filler is an inorganic substance, dicalcium phosphate
dehydrate. It is insoluble in water and also non hygroscopic but have hydrophilic property i.e.
easily wetted by water. It also has good flow ability and therefore it is used mostly in direct
compaction. [Michael, Pharmaceutics: the design and manufacture of medicines.- 3rd ed. Edinburgh : Churchill Livingstone, 2007.] [ Leon Lachman, Herbert A. Lieberman and Joseph L.
Kanig. (1991). the theory and practise of industrial pharmacy. 3rd addition: Varghese publishing
house. Page no. 293- 303.]
Disintegrants:
According to Michael, 2007, a disintegrant is added in formulation of tablet, which promotes
drug dissolution and provide an effective surface area, when comes in contact to liquid and
breaks down in small fragments. The process of disintegration for tablet occurs in main two steps
[1] Tablet wets by sold and pores it
[2] Breaks down of tablet into small fragments which include aggregation of primary particles
into small drug particles. Disintegrant suggested in some mechanism such as swelling of
particles, wetting reaction, repulsion of particle and particle recovery.
Most common types of disintegrants in tablets are maize, potato and corn starch. the
concentration of starch is up to 10% required but today normally modified starch or modified
cellulose are used which are very high swelling disintegrants. So it's requires typically 1-5% by
weight which facilitate particle-particle repulsion.
However, disintegrants can be mixed with other ingredients such as granules to increase effective
disintegration of the tablet into smaller fragments.
Leon Lachman et al, 1991, suggested that other group of disintegrants may function by
producing gas, normally carbon dioxide, in contact with water. This types of disintegrants used in
effervescent tablets and normally not in tablets that should be swallowed as a solid. The
liberation of carbon dioxide is achieved by the decomposition of carbonate salts or bicarbonate in
contact with acidic water. The acidic pH is obtained by adding citric acid and tartaric acid.
[ Michael, Pharmaceutics: the design and manufacture of medicines.- 3rd ed. - Edinburgh :
Churchill Livingstone, 2007. 3. Leon Lachman, Herbert A. Lieberman and Joseph L. Kanig.
(1991). the theory and practise of industrial pharmacy. 3rd addition: Varghese publishing house.
Page no. 293- 303]
Binder
Binder is added to the tablet or filler mixture to ensure that tablets and granules have sufficient
mechanical strength. There are several ways to add it in powderMixed with powder before wet granulation which completely or partially dissolves during
agglomeration process by agglomeration liquid.
Mixed with other ingredient as a dry powder solution before compaction process
As a solution used as agglomeration liquid during wet granulation.
Typically 2-10% of binders or dry binders are used in formulation. Most tradition common
binders are starch, sucrose and gelatine but now most common are polyvinylpyrrolidone and
cellulose derivatives which have improved adhesive properties. Examples of dry binders are
microcrystalline cellulose and crosslinked polyvinylpyrrolidone. Solution binders are most
effective therefore it is incorporated in granules.
Glidant
The role of the Glidant is to improve the flow ability of the powder. Glidants are used in
formulation for direct compaction but they are also used in granulation process before tabletting
which ensure flow ability of tablet mass for high speed production. Traditionally talc has been
used as glidant about 1-2% concentration in formulation but nowadays the most commonly used
glidant is colloidal silica added in very low proportion about 0.2% by weight.[ Michael,
Pharmaceutics: the design and manufacture of medicines.- 3rd ed. - Edinburgh : Churchill
Livingstone, 2007. 3. Leon Lachman, Herbert A. Lieberman and Joseph L. Kanig. (1991). the
theory and practise of industrial pharmacy. 3rd addition: Varghese publishing house. Page no.
293- 303]
Lubricant
The function of lubrication is to ensure low lubrication between solid and the die wall during
tablet formation and ejection. High friction during tabletting can cause a series of problems such
as inadequate tablet quality and may even stop production. Lubrication is most important which
included in most of production.
Lubrication can get by mainly two mechanism, fluid lubrication and boundary lubrication. In
fluid lubrication, liquid is achieved between die surface and tablet surface which separates the
moving surfaces of the solids from each other and reduces the friction. While in boundary
lubrication, it is considered as a surface phenomenon, as here moving surface is separated by a
very thin layer of lubricants. Such boundary lubricants are Stearic acid salts, primarily
Magnesium Stearate which is most widely use due to its superior lubrication properties. Besides
reducing friction, lubricants may also causes undesirable changes such as reducing tablet
strength with bonding between the particles during compaction. Because of hydrophobic
properties of lubricants, tablet disintegration and dissolution are often retarded by the addition of
lubricants. Thus, minimum amount of lubricants are used, i.e. concentrations of 1% or below,
often 0.25-0.5%.in order to avoid these negative effects, more hydrophilic substances have been
suggested as alternatives to the hydrophobic lubricants. For example, surface active agents and
polyethylene glycols and sometimes a combination of hydrophilic and hydrophobic substances
might also be used. [M. E Aulton, Pharmaceutics, The Science of Dosage Form Design, Second
Edition, 2002, pp.408-412]
Antiadherent
Antiadherent are substance which reduce adhesion between powder and punch faces which
prevent sticking of particles to punches. The sticking is mainly affected by moisture content of
the powder. Such adherence especially prone to happen if the tablet punches have marking or
symbols which lead to a build of thin layer of powder on the punches which in turn will lead to
an uneven and matt tablet surface with unclear markings or symbols. Some lubricants such as
Magnesium Stearate have also antiadherent properties. However, other substances with limited
ability to reduce friction can also act as antiadherent such as talc and starch. [M. E Aulton,
Pharmaceutics, The Science of Dosage Form Design, Second Edition, 2002, pp.408-412]
Sorbents
Sorbents are substances which has capacity to sorbing some quantities of fluid into dry state. So
oil and oil-drug solutions can be incorporated into mixture of powder and compacted into tablets.
Most commonly used sorbents are Microcrystalline Cellulose and Silica. [M. E Aulton,
Pharmaceutics, The Science of Dosage Form Design, Second Edition, 2002, pp.408-412]
Flavouring agents
Flavouring agents are incorporated into a formulation to remove unpleasant taste of bitter drug or
to make tablet more pleasant or mask. This can be achieved by coating or by adding some drug
particles. Most of Flavouring agents are thermolabile so it cannot be added in process which
involve heating. They are mixed with granules as alcoholic solution.
Colouring agents
The aim to add colourant is to aid identification of tablet, improve looks of tablet and patient
compliance. Mostly, colourant are added during coating of tablet but some of colourant may be
added in formulation prior to compaction. Colourant may be added as an insoluble powder or
dissolved in granulation liquid and the latter procedure may produce colour variation by
migration of soluble dye during drying stage.
Wet granulation
Granulation is process in which primary powder particles are made to form large and these types
of multi particle called granules. In pharmaceutical industry, granules are useful in production of
tablets and capsules in ranges of particle size between0.2 to 0.5mm.
Granulation prevents segregation of constituents of powder, improve flow ability of powder,
improve compaction characteristics of mixture and reduce toxic dust.
Wet granulation is widely used method for production of compressed tablets which include
flowing steps-
compatibility with formulation. Among the fillers, lactose is most preferred because of its
solubility and compatibility, and microcrystalline cellulose, because of its easy compaction
compatibility and consistent uniformity of supply.
Disintegrating agents include croscarmellose, corn and potato starches, sodium starch glycolate,
sodium carboxymethylcellulose, polyvinyl polypyrrolidone (PVP), cation exchange resins,
alginic acid and other materials which swell or expand on exposure to moisture and helps to
breakup tablets in gastrointestinal track (GIT). Mainly croscarmellose and sodium starch
glycolate are used because of their high water uptake and rapid action. Mostly up to 5-10% of
starch is suitable for formulation, but up to about 20% may be used to facilitate more rapid tablet
disintegration. The total amount of disintegrant is not always used but sometime it added in
preparation of granulation and sometime half of it added to tablet formation which called double
disintegration of tablet. One portion of disintegrant assist breakup of tablet into pieces and other
portion breakup pieces into particles.
Dry granulation
In this method, powder mixer is compressed in large pieces and subsequently broken down or
sized into granules. In this method, either active ingredient or diluent must have cohesive
properties. This method is basically applied to materials which cannot be prepared by wet
granulation because of moisture degradation properties or thermo-mobile properties of granules.
It is carried out by two steps:
Slugging:
After weighing and the mixing of ingredients, the powder mixture is slugged or compressed into
large flat tablets about one inch in diameter. Slugs are than broken up hand or mill and passed
through a screen of desired mess for sizing and sometimes lubricant are added and prepared by
compression.
Roller compaction:
Instead of slugging, powder compactors may be used to increase the density of a powder by
pressing it between rollers at 1 ton to 6 tons of pressure. The compact material is broken up,
sized, and lubricated, and tablets are prepared by compression. Commonly used binding agents
are methyl cellulose or hydroxylmethyl cellulose (6-12%) which produces good hardness and
friability of tablet.
Figure (C) Tablet compression by Dry Granulation [Pharmaceutics - I, P.V. KASTURE, S.R.
PARAKH, S.A. HASAN, S.B. GOKHALE, June 2008, pp-14-7, 21]
Tableting of granulation:
There are different types of tabletting machines which are used in the productivity but similar in
basic function and operation. They all compress tablet formulation within steel die cavity by the
pressure exerted by the movement of two steel punches, lower punch and an upper punch.
Weight variation:
This is very important in process control measurement. If anything that can alter the die filling
process can alter tablet weight, it causes weight variation because the weight of the tablet being
compressed is determined by the amount of the granulation in the die prior to compression. Some
causes of variation are large granules, poor mixing of granules with lubricants and glidants, poor
granulation flow from hopper, double impression and punch variation.
Picking
Picking is the term used to describe the surface material from tablet that is sticking to being
removed from the tablet's surface by a punch. It concerns when punching tips have engraving or
embossing
Sticking
Sticking is usually referred to adhesion of tablet material to die wall. Because of that, lower
punch cannot move freely and additional force is required to overcome friction between die wall
and the tablet. These problems can be solved by design large lettering, adding polishing agent
such as colloidal silica or additional lubricants. Some low melting point substances such as
polyethylene glycol may also cause sticking at the heat of compression. Such Remedies are
addition of high melting point materials and consequently increasing size of tablet.
Mottling:
Mottling is term used unequal distribution of colour on a tablet with light and dark areas. It's due
to colour difference of drug with excipients or drugs whose degradation product is coloured.
Such problems might be solved by using colorants but it can cause mottling on the top of surface
when granulation undergoes drying. To overcome difficulties, it require to change solvent
system, binder system and by reducing temperature.
Tablet coating
Tablet coating is application of coating of material to the exterior of tablet with some intentional
benefits. It is also intended for modified release applications.
Main three types of coating areFilm coating
Sugar coating
Press coating
Coating of tablets are for following purposes[1] Protection from environment, light and moisture
[2] To remove bitter taste of some tablets and for easy swallowing of tablets
[3] Colour coating mask differences in appearance which effect on patient compliance
[4] Rapid identification by manufacturer, pharmacist and patient
Film coating
This is more modern and widely used for tablet coating. Most of newly launched coated products
are film coated rather than sugar coating.
Film coating involves covering of tablet by thin film layer of coating liquid (polymer). Coating
liquid is sprayed in a rotating tablet bed or bed fluidised tablet which contains plasticizer,
polymer, colourant and solvent. The drying condition permits removal of solvent and leaves a
thin layer around each tablet. Sometimes aqueous solution or organic solutions are used to reduce
elimination of volatile organic compound, health and safety and cost reduction purposes. Film
coating polymer should have following properties[1] Optimum solubility to facilitate dissolution of final product. High soluble for immediate
release and low soluble for controlled release.
[2] Optimum viscosity to permit and trouble free spraying of solution.
[3] Optimum permeability to optimize shelf life of tablet preparation and some tuned to provide
an effective barrier oxygen and water vapour.
[4] Good mechanical strength to withstand the impact and abrasion encountered in normal
handling which avoids cracks and imperfections.
Cellulose derivatives like Hydroxypropylmethylcellulosa (HPMC), methylcellulose,
hydroxypropylcellulose (HPC) and Methacrylate amino ester copolymer are available polymer
for film coating.
Sugar coating
Sugar coating involves the successive application of sucrose based solutions to tablet cores in
suitable equipment. Some stages in production of sugar coated tablets are[1] Sealing of tablet core- provide water proofing core from coating process and shellac,
cellulose acetate phthalate are normally used in sealing process.
[2] Sub coating- it is the actual start of sugar coating which provides necessary build-up to
roundup the tablet edge. Bulking agents such as calcium carbonate or talc added in sucrose
solution with gum.
[3] Smoothing - it increases tablet size to predetermined dimension by syrup solution. This
solution contains pigments, starch, gelatine, acacia or opacifier.
[4] Colouring- dyes or pigments
[5] Polishing- tablets need to be polished to achieve final elegance by waxes like beeswax,
carnubawax or hard paraffin.
[6] Printing
Enteric coating
According to Biju et al 2004, [BIJU, S. S.; SAISIVAM, S.; RAJAN, M. G.; MISHRA, P. R. Dual
coated erodible microcapsules for modified release of Diclofenac sodium. Eur. J. Pharm
Biopharm., v.58, n.1, p.61-67, 2004. ] enteric polymer technique is safe and widely used in drug
products. Enteric coating prefers small intestine so it prevents the disintegration of tablet in the
acidic environment of stomach and release into small intestine for some reasons such as
Prevention of acid attack on active constituents at low pH
Protect stomach from irritation from drug
Facilitate absorption of drug which is preferentially absorbed distal to stomach.
Most commonly used enteric coating polymers are Cellulose acetate phthalate, Polyvinyl acetate
phthalate, suitable acrylic derivatives and Hydroxypropyl methyl cellulose phthalate because
they are free from carboxylic acid group and different pH solubility profile. They are almost
insoluble at low pH and increases solubility at specific pH such as pH 5.2 for cellulose acetate
phthalate. Enteric coating is possible for both sugar and film coating.
Peters et al, 1993[PEETERS, R.; KINGET, R. Film-forming polymers for colonic drug delivery:
I Synthesis and physical and chemical properties of methyl derivatives of Eudragit S. Int. J.
Pharm., v.94, n.1-3, p.125-134, 1993. ] stated that there are number of polymers are available
which are insoluble at low pH but dissolve at pH around or below 7. Shellac ia natural enteric
polymer which is gastric resistance. Hydroxypropyl methyl cellulose was first polymer in
contract to ethyl cellulose which is used a novel enteric coating agents for acid protection
because it is water soluble and leach of film coating which diffuses drug more rapidly than ethyl
cellulose.[ Kokubo et al, 1997, Gunder, Lippold, 1995].[ KOKUBO, H.; OBARA, S.;
MINEMURA, K.; TANAKA, T. Development of cellulose derivatives as novel enteric coating
agents soluble at pH 3.5-4.5 and higher. Chem. Pharm. Bull. (Tokyo), v.45, n.8, p.1350-1353,
1997., GUNDER, W.; LIPPOLD, B. H.; LIPPOLD, B. C. Release of drugs from ethyl cellulose
microcapsules (diffusion pellets) with pore formers and pore fusion. Eur. J. Pharm. Sci., v.3,
n.12, p.203-214, 1995.] A continuous technology coating is use to water instead of organic
solvents to minimize environmental and safety hazards so Baudoux et al 1990, [BAUDOUX, M.;
DECHESNE, J. P.; DELATTRE L. Film Coating with Enteric Polymers from Aqueous
Dispersions. Pharm. Tech. Int., v.12, n.11, p.18-26, 1990.] stated that water based technology is
being widely used instead of organic system.
Evolution of tablets
After production, tablets must be evaluated to check qualitative and quantitative analysis and
chemical, physical and bioavailability properties. For that reason, evaluation is classified in three
different categories.
General appearance:
Size and shape
Unique identification markings
Organoleptic properties such as colour, odour and taste.
Mechanical strength:
Hardness test
Friability test
Tensile test
Brittle fracture index
These evolution tests are specific standard in each pharmacopeia. Specification may be vary to
one country from other. All products have regulatory aspects which must be complied for that
particular product.
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