TABLET
Tablet is defined as a compressed solid dosage form containing medicament's with or without excipients. According to IP Pharmaceutical tablets are solid, flat or biconvex dishes, unit dosage form, prepared by compressing a drugs or a mixture of drugs, with or without diluent
v They vary in shape and differ greatly in size and weight, depending on amount of medicinal substances and the intended mode of administration.
v Most popular dosage form and 70% of the total medicines are dispensed in the form of Tablet.
v All medicaments are available in the Tablet form except where it is difficult to formulate or administer.
Advantages of the Tablet dosage forms:
1. Unit dosage form and offer the greatest capabilities of all oral dosage form for the greatest dose precision and the least content variability.
2. Cost is lowest of all oral dosage form.
3. Lighter and compact.
4. Easiest and cheapest to package and strip.
5. Easy to swallowing with least tendency for hang-up.
6. Sustained release product is possible by coating.
7. Objectionable odour and bitter taste can be masked by coating technique.
8. Suitable for large scale production.
9. Greatest chemical and microbial stability over all oral dosage form.
10. Product identification is easy and rapid requiring no additional steps when employing an embossed and/or monogrammed punch face.
Disadvantages of Tablet dosage forms:
1. Difficult to swallow in case of children and unconscious patients.
2. Some drugs resist compression into dense compacts, owing to amorphous nature, low density character.
3. Drugs with poor wetting, slow dissolution properties, may be difficult to formulate or manufacture as a tablets
4. Bitter testing 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. 2
General properties of Tablet dosage forms:
1. A tablet should have elegant product identity while free of defects like chips, cracks, discoloration, and contamination.
2. Should have sufficient strength to withstand mechanical shock during its production packaging, shipping and dispensing.
3. Should have the chemical and physical stability to maintain its physical attributes over time
4. The tablet must be able to release the medicinal agents in a predictable and reproducible manner.
5. Must have a chemical stability over time so as not to follow alteration of the medicinal agents.
Tablet Ingredients
In addition to active ingredients, tablet contains a number of inert materials known as additives or excipients. Different excipients are:
1. Diluent
2. Binder and adhesive
3. Disintegrents
4. Lubricants and glidants
5. Colouring agents
6. Flavoring agents
7. Sweetening agents
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.
Selection of the Diluent
Is based partly on the experience of the manufacturer as well as on diluent cost and compatibility with other tablet ingredients
However, in the formulation of new therapeutic agents, the compatibility of the diluents with the drug must be considered, e.g: calcium salts used as diluents for the broad-spectrum antibiotic tetracycline have been shown to interfere with the drug’s absorption from the gastrointestinal tract.
When drug substances have low water solubility, it is recommended that water-soluble diluents be used to avoid possible bioavailability problems.
There cost must be low
They must be free from all microbial contamination
They must be color compatible
Should not exert deleterious effect on drug bioavailability
Highly adsorbent substances, e.g, bentonite and kaolin, are to be avoided in making tablets of drugs used clinically in small dosage, such as the cardiac glycosides, alkaloids and the synthetic estrogens. These drug substances may be adsorbed after administration.
The combination of amine bases with lactose, or amine salts with lactose in the presence of an alkaline lubricant, results in tablets which discolor on aging.
Microcrystalline cellulose (Avicel) usually is used as an excipient in direct-compression formulas.
However, its presence in 5-15% concentrations in wet granulations has been shown to be beneficial in the granulation and drying processes in minimizing core-hardening of the tablets and in reducing tablet mottling.
Many ingredients are used for several different purposes, even within the same formulation; e.g, corn starch can be used in paste form as binder, in dry form as disintegrant.
Commonly used tablet diluents
- Lactose-anhydrous and spray dried lactose
Most commonly used
Lactose formulation show good drug release
Granules are rapidly dried
GRADES 60-80 mesh-coarse
80-100 mesh-regular
Maillard reaction-hydrous lactose
2. Directly compressed starch-Sta Rx 1500
may be used as diluent, binder and/or disintegrant
3. Hydrolyzed starch-Emdex and Celutab
90-92% dextrose
3-5% maltose
free flowing and directly compressible
May be used in place of mannitol in chewable tablets due to sweetness and smooth feeling in mouth
Commonly used tablet diluents
4. Microcrystalline cellulose-Avicel (PH 101 and PH 102)
Free flowing and excellent compression property
Relatively expensive and is used in combination with other ingredients
5. Dibasic calcium phosphate dehydrate
6. Calcium sulphate dihydrate
7. Mannitol
8. Sorbitol
9. Sucrose- Sugartab, DiPac, Nutab
10. Dextrose
Cellulose derivatives- Methyl cellulose, Hydroxy propyl methyl cellulose, Hydroxy propyl cellulose
Direct compression- used dry and have binder capabilities
Aqueous solution-adhesive properties
HPC may be used as alcoholic solution-anhydrous binder
Glucose- 50% solution
Polyvinylpyrrolidone (PVP)- 2% conc.
Synthetic polymer
Used as an aqueous and alcoholic solution
Starch paste-10-20% solution
Sodium alginate
Sorbitol
Cellulose derivatives- Methyl cellulose, Hydroxy propyl methyl cellulose, Hydroxy propyl cellulose
Direct compression- used dry and have binder capabilities
Aqueous solution-adhesive properties
HPC may be used as alcoholic solution-anhydrous binder
Glucose- 50% solution
Polyvinylpyrrolidone (PVP)- 2% conc.
Synthetic polymer
Used as an aqueous and alcoholic solution
Starch paste-10-20% solution
Sodium alginate
Sorbitol
The quantity of binder used has considerable influence on the characteristics of the compressed tablets.
The use of too much binder or too strong a binder will make a hard tablet which will not disintegrate easily and which will cause excessive wear of punches and dies.
Usually materials which have no cohesive qualities of their own will require a stronger binder than those with these qualities.
Binders are used both as a solution and in a dry form depending on other ingredients and method of preparation.
The same amount of binder in solution will be more effective than if it were in a dry form and moistened with the solvent. So it is preferable to incorporate the binding agent in solution.
If the drug substance is adversely affected by an aqueous binder , a non aqueous binder can be used or binder can be added dry.
The direct-compression method for preparing tablets requires a material that not only is free-flowing but also sufficiently cohesive to act as a binder.
Disintegrants
A substance, or a mixture of substances, added to a tablet to facilitate its breakup or disintegration after administration.
Function by drawing water into the tablet, swelling and causing the tablet to burst
Materials serving as disintegrants have been classified chemically as starches, clays, celluloses, algins, gums and cross-linked polymers.
Starch- 5-15% of tablet weight.
Starch derivative – Primogel and Explotab (1-8%)
Clays- Veegum HV, bentonite 10% level in colored tablet only
Cellulose
Cellulose derivatives- Ac- Di-Sol (internally crosslinked form of sodium carboxy methyl cellulose)
Alginate
PVP (Polyvinylpyrrolidone), cross-linked
The oldest and still the most popular disintegrants are corn and potato starch which have been well-dried and powdered.
Starch has a great affinity for water and swells when moistened, thus facilitating the rupture of the tablet matrix.
Others suggested that its disintegrating action in tablets is due to capillary action rather than swelling.
Starch 5%, is suggested, but if more rapid disintegration is desired, this amount may be increased to 10 or 15%.
Primogel and Explotab are low substituted carboxymethyl starches and are used in low concentration
Usually disintegration time would decrease as the percentage of starch increased.
A group of materials known as super disintegrants have gained in popularity. As Croscarmelose, crospovidone and sodium starch glycolate
The name comes from the low levels (2 to 4%) at which they are completely effective.
Sodium starch glycolate swells 7-12 fold in less than 30 seconds. Croscarmelose swells 4-8 fold in less than 10 seconds.
The disintegrating agent usually is mixed with the active ingredients and diluents prior to granulation.
In some cases it may be advantageous to divide starch into two portions:
One part is added to the powdered formula prior to granulation, and the remainder is mixed with the lubricant and added prior to compression.
Incorporated in this manner, the starch serves a double purpose; the portion added to the lubricant rapidly breaks down the tablet to granules, and the starch mixed with the active ingredients disintegrates the granules into smaller particles.
Lubricants-reduce the friction during tablet ejection between the walls of the tablet and walls of the die cavity
Antiadherants-Purpose of reducing sticking or adhesion of granules or powder to the faces of punch or die wall
Glidants- intended to increase the flow properties of granules or power materials by reducing friction between particles
Examples:
Lubricants- Stearic acid, Stearic acid salt
Most commonly used
Talc
second most common
Most lubricants, with the exception of talc, are used in concentrations less than 1%. When used alone, talc may require concentrations as high as 5%.
Lubricants are in most cases hydrophobic materials. Poor selection or excessive amounts can result in “waterproofing” the tablets, resulting in poor tablet disintegration and or delayed dissolution of the drug substance
Antiadherants- Most of the lubricant materials except water soluble are used as Antiadherants
Glidants are intended to promote flow of granules or powder material by reducing the friction between the particles.
Corn Starch – 5-10% conc., Talc-5% conc.,
Silica derivative - Colloidal silicas such as Cab-O-Sil, Syloid, Aerosil in 0.25-3% conc.
Coloring agent: The use of colors and dyes in a tablet has three purposes:
(1) Masking of off color drugs
(2) Product Identification
(3) Production of more elegant product
All coloring agents must be approved and certified by FDA. Two forms of colors are used in tablet preparation – FD &C and D & C dyes. These dyes are applied as solution in the granulating agent or Lake form of these dyes. Lakes are dyes absorbed on hydrous oxide and employed as dry powder coloring.
Example: FD & C yellow 6-sunset yellow
FD & C yellow 5- Tartrazine
FD & C green 3- Fast Green
FD & C blue 1- Brilliant Blue
FD & C blue 2 - Indigo carmine
D & C red 3- Erythrosine.
D & C red 22 – Eosin Y
Flavoring agents
Are usually limited to chewable tablets or tablets intended to dissolve in the mouth.
Generally, water-soluble flavors have poor stability; hence, flavor oils or dry powders usually are used.
Flavor oils may be added to tablet granulations in solvents, dispersed on clays and other adsorbents, or emulsified in aqueous granulating agents.
Usually, the maximum amount of oil that can be added to a granulation without influencing its tablet characteristics is O.5%—O.75%.
Sweetening agents
Used only with chewable tablets or tablets dissolve in the mouth.
Some sweetness may come from the diluent (e.g., mannitol, lactose);
agents, such as saccharin and aspartame, can also be added.
Saccharine (artificial): 500 times sweeter than sucrose
Disadvantage: Bitter aftertaste and carcinogenic
Aspartame (artificial)
Disadvantage: Lack of stability in presence of moisture.
TABLET GRANULATIONS
Granulation Properties
Many formulation and process variables are involved in granulation step and all can affect the characteristics of granules
Particle size and shape
Size of granules can affect- average tablet weight, weight variation, granule friability, granulation flowability and drying rate kinetics of wet granulations
Surface area
May be of value for drugs that have poor water solubility and can have impact on dissolution rate
Density
Influence compressibility, tablet porosity, dissolution
Strength and friabilty
can affect- changes in particle size distribution of granulations and consequently compressibility into cohesive tablets
Flow properties
Extremely important parameter
Affect distribution of granules with consequent anomaly in weight and drug content
Flow properties Angle of repose
Hopper flow rates
Wet Granulation
The most widely used and most general method.
This is due to the greater probability that the granulation will meet all the physical requirements for the compression of good tablets.
Its chief disadvantages are the number of separate steps involved, as well as the time and labor necessary to carry out the procedure, especially on a large scale.
The steps in the wet method are:
1-weighing 2-mixing
3-granulation 4-screening the damp mass
5- drying 6-dry screening
7-lubrication 8-compression.
The active ingredient, diluent and disintegrant are mixed or blended well.
The powder blend may be sifted through a screen to remove or break up lumps, this screening affords additional mixing.
The screen selected always should not affect the potency of the ingredients through interaction. For example, the stability of ascorbic acid is affected deleteriously by even small amounts of copper, thus care must be taken to avoid contact with copper or copper-containing alloys
Solutions of the binding agent are added to the mixed powders with stirring.
The powder mass is wetted with the binding solution until the mass has the consistency of damp snow
May take from 15 min to an hour depending on wetting properties of powder mixture and the granulating fluid and efficiency of mixer
If the 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
Damp mass is passed through oscillating granulator having large perforations
Drying of granules
Tray drying was most widely used method of drying tablet granulations Newer methods being introduced are the fluid-bed dryers
In fluidization, the material is suspended and agitated in a warm air stream while the granulation is maintained in motion.
Fluidized bed dryer- 15 times faster than the conventional tray dryers
If the 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
Damp mass is passed through oscillating granulator having large perforations
Drying of granules
Tray drying was most widely used method of drying tablet granulations Newer methods being introduced are the fluid-bed dryers
In fluidization, the material is suspended and agitated in a warm air stream while the granulation is maintained in motion.
Fluidized bed dryer- 15 times faster than the conventional tray dryers
Fluidization method- Advantages eg. better control of drying temperatures, decreased handling costs and the opportunity to blend lubricants and other materials into the dry granulation directly in the fluidized bed.
In drying, it is desirable to maintain a residual amount of moisture in the granulation. This is necessary to maintain the various granulation ingredients such as gums in a hydrated state.
Also, the residual moisture contributes to the reduction of the static electric charges on the particles.
In the selection of any drying process, an effort is made to obtain a uniform moisture content.
In addition to the importance of moisture content of the granulation in its handling during the manufacturing steps, the stability of the products containing moisture-sensitive active ingredients may be related to the moisture content of the products.
Water-soluble colorants can migrate toward the surface of the granulation during the drying process, resulting in mottled tablets after compression.
This is also true for water-soluble drug substances, resulting in tablets unsatisfactory as to content uniformity.
Migration can be reduced
by drying the granulation slowly at low temperatures OR
using a granulation in which the major diluent is present as granules of large particle size
The presence of microcrystalline cellulose in wet granulations also reduces migration tendencies.
After drying, the granulation is reduced in size by passing through screen.
Lubricant is added as a fine powder and compressed
Equipments
Littleford Lodige mixer
Capable of blending pharmaceutical powder and wet massing within the same equipment
Diosna mixer/granulator
High speed powder mixer and processor
Littleford MGT mixer/granulator
Gral mixer/granulator
Dry Granulation
When tablet ingredients are sensitive to moisture or are unable to withstand elevated temperatures during drying, and when the tablet ingredients have sufficient inherent binding or cohesive properties, slugging may be used to form granules.
This method is referred to as dry granulation, pre compression or double-compression.
Many aspirin and vitamin formulations are prepared by this method
It eliminates a number of steps but still includes weighing, mixing, slugging, dry screening, lubrication and compression.
The active ingredient, diluent (if one is required) and part of the lubricant are blended
One of the constituents, either the active ingredient or the diluent, must have cohesive properties
Compacted by means of flat faced punches
Compact mass-slugs (Chilsonator roller compactor)
Powdered material contains a considerable amount of air; under pressure this air is expelled and a fairly dense piece is formed
The more time allowed for this air to escape, the better the tablet or slug
Slugs are screened or milled to produce granular material
The lubricant remaining is added to the granulation, blended gently and the material is compressed into tablets.
Direct Compression
Direct compression consists of compressing tablets directly from powdered material without modifying the physical nature of the material itself.
Reserved for a small group of crystalline chemicals having all the physical characteristics required for the formation of a good tablet
For tablets in which the drug itself constitutes a major portion of the total tablet weight, it is necessary that the drug possess those physical characteristics required for the formulation to be compressed directly.
Direct compression for tablets containing 25% or less of drug substances frequently can be used by formulating with a suitable diluent which acts as a carrier or vehicle for the drug
These properties are imparted to them by a preprocessing step such as wet granulation, slugging, spray drying, or crystallization
Directly compressible vehicles: anhydrous lactose, spray-dried lactose, pregelatinized starch, compressible sugar, mannitol and microcrystalline cellulose.
These commercially available direct- compression vehicles may contain small quantities of other ingredients (e.g, starch) as processing aids. Dicalcium phosphate dihydrate (Di-Tab,)
Compressible sugar consists mainly of sucrose that is processed to have properties suitable for direct compression
It also may contain small quantities of dextrin, starch or invert sugar
It is a white crystalline powder with a sweet taste and complete water solubility
It requires the incorporation of a suitable lubricant at normal levels for lubricity
The sugar is used widely for chewable vitamin tablets because of its natural sweetness
One commercial source is Di-Pac (Amstar) prepared by the cocrystallization of 97% sucrose and 3% dextrins.
Some forms of lactose meet the requirements for a direct-compression vehicle.
HYDROUS LACTOSE
does not flow- Limited to tablet formulations prepared by the wet granulation method,
ANHYDROUS LACTOSE AND SPRAY DRIED LACTOSE
Good flowability and compressibility and can be used in direct compression provided a suitable disintegrant and lubricant are present.
MICROCRYSTALLINE CELLULOSE (Avicel, FMC).
Available in several grades which range in average particle size from 20 to 100 um.
Swells on contact and thus acts as a disintegrating agent
The material flows well and has a degree of self-lubricating qualities, thus requiring a lower level of lubricant as compared to other excipients.
EVALUATION OF TABLETS
General Appearance:
The general appearance of a tablet, its identity and general elegance is essential
v for consumer acceptance
v for control of lot-to-lot uniformity
v tablet-to-tablet uniformity
The control of general appearance involves the measurement of size, shape, color, presence or absence of odor, taste etc.
Size & Shape:
Tablet thickness can be measured by micrometer or by other device
Tablet thickness should be controlled within a ± 5% variation of standard value.
Unique identification marking:
These marking utilize some form of embossing, engraving or printing
These markings include company name or symbol, product code, product name etc.
Organoleptic properties:
Color distribution must be uniform with no mottling
For visual color comparison compare the color of sample against standard color.
Hardness:
To withstand the mechanical shocks of manufacture, packaging, and shipping,
To ensure consumer acceptance
Hardness relates to both tablet disintegration and to drug dissolution
Certain tablets intended to dissolve slowly are made hard, whereas others intended to dissolve rapidly are made soft
Hardness tester
Monsanto Strong-Cobb
Pfizer Erweka
Schleuniger
Weight Variation test:
Take 20 tablet and weighed individually
Calculate average weight and compare the individual tablet weight to the average
The tablet pass the test if no more that 2 tablets are outside the percentage limit and if no tablet differs by more than 2 times the percentage limit.
Average weight (mg) Max % difference allowed
130 or less 10
130-324 7.5
More than 324 5
Content Uniformity Test:
Randomly select 30 tablets
10 of these assay individually
v 9 of the 10 tablets must contain not less than 85% and not more than 115% of the labeled drug content
v None of the tablet must be outside 75-125% range
v If these conditions are not met
further 20 tablets are assayed & all must fall within 85-115%
Disintegration Test:
v The apparatus consists of a basket rack holding six plastic tubes, open at the top and bottom; the bottom of the tubes is covered with 10-mesh screen
v The basket rack is immersed in a bath of suitable liquid, held at 37°, preferably in a 1 -L beaker
v The rack moves up and down in the fluid at a specified rate
v The volume of the fluid is such that on the upward stroke the wire mesh remains at least 2.5 cm below the surface of the fluid and descends to not less than 2.5 cm from the bottom on the downward stroke
v Tablets are placed in each of the six cylinders along with a plastic disc over the tablet unless otherwise directed in the monograph
v The end-point of the test is indicated when any residue remaining is a soft mass having no soft core
Move the basket containing the tablets up and down through a distance of 5-6 cm at a frequency of 28 to 32 cycles per minute
Floating of the tablets can be prevented by placing perforated plastic discs on each tablet.
For compressed uncoated tablets the testing fluid is usually water at 37°, but in some cases the monographs direct that Simulated Gastric Fluid be used
If one or two tablets fail to disintegrate, the test is to be repeated using 12 tablets Of the 18 tablets then tested, 16 must have disintegrated within the given period of time
For most uncoated tablets the period is 30 minutes although the time for some uncoated tablets varies greatly, from this. For coated tablets up to2 hours may be required, while for sublingual tablets, the disintegration time is 3 minutes.
Dissolution Test
For tablet containing slowly or poorly soluble drug determination of dissolution rate may be more important than measuring tablet disintegration time
The dissolution test measures the amount of time required for a given percentage of the drug substance in a tablet to go into solution under a specified set of conditions is an in vitro test.
It provide a step towards the evaluation of the physiological availability of the drug substance, but it is not designed to measure the safety or efficacy of the tablet being tested
Apparatus-1:
A single tablet is placed in a small wire mesh basket attached to the bottom of the shaft connected to a variable speed motor.
The basket is immersed in a dissolution medium (as specified in monograph) contained in a 1000 ml flask
The flask is cylindrical with a hemispherical bottom
The flask is maintained at 37±0.50C by a constant temperature bath
The motor is adjusted to turn at the specified speed and sample of the fluid are withdrawn at intervals
Amount of the drug is estimated using appropriate method
Apparatus-2:
It is same as apparatus-1, except the basket is replaced by a paddle.
The dosage form is allowed to sink to the bottom of the flask before stirring.
The test tolerance is expressed as a % of the labeled amount of drug dissolved in the time limit.
T70%- 45 Min
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Different types of Tablets
(A) Tablets ingested orally:
1. Compressed tablet, e.g. Paracetamol tablet
2. Multiple compressed tablet
layered tablets
compression coated tablets
3. Repeat action tablet
4. Delayed action and enteric coated eg. Bisacodyl tablet
5. Sugar coated tablet, e.g. Multivitamin tablet
6. Film coated tablet, e.g. Metronidazole tablet
7. Chewable tablet, e.g. Antacid tablet
(B) Tablets used in oral cavity:
1. Buccal tablet, e.g. Vitamin-c tablet
2. Sublingual tablet, e.g. Vicks Menthol tablet
3. Troches or lozenges
4. Dental cone
(c) Tablets administered by other routes:
1. Implantation tablet
2. Vaginal tablet, e.g. Clotrimazole tablet
(D) Tablets used to prepare solution:
1. Effervescent tablet, e.g. Dispirin tablet (Aspirin)
2. Dispensing tablet, e.g. Enzyme tablet (Digiplex)
3. Hypodermic tablet
4. Tablet triturates e.g. Enzyme tablet (Digiplex)
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Solvents
Should either dissolove or disperse the polymer systems
Easily disperse other coating solution compositions into the solvent system
2-10% polymer-no extreme viscocity
Colourless, odourless, tasteless, inexpensive, nontoxic, inert, non-iflammable
Rapid drying rate
Water, ethanol, methanol, DCM, acetone
Plasticizer
Modify the quality of the polymeric film
Internal
External
INTERNAL MATERIALS
Modify the chemical properties of the polymer- changes the chemical properties of the polymer
EXTERNAL MATERIALS
Non-volatile or the other polymer-include with primary polymeric film former and changes
Flexibility
Tensile strength
Adhesion properties of the resulting film.
Choice of the plasticizer material depends:
Ability of plasticizer material to solvate the polymer
EXAMPLES : Castor oil; propylene glycol of 200 and 400 series; and surfactants eg; Tweens; Spans; and organic acid esters
WATER- SOLUBLE PLASTICIZER : PEG, propylene glycol.
ORGANIC- SOLUBLE PLASTICIZER : Castor-oil and SPANS.
COLORANTS
soluble in the solvent system
suspended as insoluble powders.
Used to provide distinctive color and elegance to a dosage form
Proper distribution- use of fine-powdered colorants (< 10 microns)
Most of colorants are synthetic DYES or LAKES OF DYES approved by the FD & C and D&C
LAKES : derived from dyes by precipitating with carriers. Eg ; alumina or talc. Lakes contains 10 to 30 % of the pure dye content.
For very light shade, concentration : less than 0.01 %.
For dark shade, concentration : more than 2.0 % .
EXAMPLES :
Inorganic materials
Iron oxides
Natural coloring materials
Anthocyanins, caramel, carotenoids,
chlorophyll, indigo, flavones
turmeric and carminic acid
Commercially available coating solution:
◊ Opalux – Opaquant color concentrate for sugar coating.
◊ Opaspray- Opaque color concentrate for film coating.
◊ Opadry – Complete film coating concentrate.
Opaquant-Extenders
Very fine inorganic powders used in the coating solution formulation
more pastel colors
increase film coverage
Opaquant provides a white coating or mask the color of the tablet core
thus the less amount of the colorants are required
Examples :
Silicates(talc, aluminium silicate)
Carbonates(magnesium carbonate)
Sulfates(calcium sulfate)
Oxides(Mg oxides)
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SEAL COATING
rationale?
To prevent the moisture penetration into the tablet core, a seal coat is applied
shellac- effective sealant
lengthening of tablet disintegration and dissolution
Zein is an alcohol-soluble protein derivative from corn
No lengthening; dissolution times
SUBCOATING
rationale?
Applied to round the edges and build up the tablet size
Increase the tablet weight by 50 to 100%.
SYRUP SMOOTHING
Covers and fill the imperfection in the tablet surface caused by the subcoating step
Impart the desired color to the tablet
Glossing syrup :
The first syrup coats-contains the suspended powders
Colorants can be added to this syrup.
In the second step-syrup solution containing the dye are applied until the final size and color are achieved.
In the final step-a few clear coats of syrup may be applied.
POLISHING
Tablets can be polished in clean standard coating pans, or canvas-lined polishing pans
by careful application of the powdered wax (beeswax or carnauba)
OR warm solution of these waxes in naphtha or other suitable volatile solvents.
Simplified representation of sugar coating process
FILM COATING
Process in which a thin (20-200 mm) polymer based film is applied
Coating systems are initially liquid
Polymeric Solutions
Polymeric Dispersions
Coating process involves the conversion of a liquid into a dry amorphous solid (film)
Mechanism
Film formation is dependent on the coalescence of polymer particles into a continuous film.
coalescence can extend into months if appropriate coating conditions are not used
Process of film formation very sensitive to process conditions used.
Schematic Representation of Film Coating Process
Polymer used in film coating
Cellulose derivatives
Methacrylate amino ester copolymers.
Plasticizer used in film coating
Polyols - Polyethylene glycol 400
Organic esters - diethyl phthalate
Oils/glycerides - fractional coconut oil
Colourants used in film coating
Iron oxide pigments
Titanium dioxide
Aluminium lakes.
Water insoluble pigments are more favourable than water soluble colours:
ü Better chemically stability in light
ü Optimised impermeability to water vapour
ü Better opacity
ü Better covering ability
ENTERIC COATING
protection of the tablet core from disintegration in the acidic environment of the stomach
Aims of Enteric protection:
ü To mask taste or odour
ü Protection of active ingredients, from the acidic environment of the stomach.
ü Protection from local irritation of the stomach mucosa.
ü Release of active ingredient in specific target area within gastrointestinal tract.
The pH status of enteric coated polymers in the stomach
SMALL INTESTINE
The polymers used for enteric coatings remain unionise at low pH, and therefore remain insoluble. As the pH increases in the gastrointestinal tract the acidic functional groups are capable of ionisation, and the polymer swells or becomes soluble in the intestinal fluid.
Enteric polymeric film coating allows the coated solid to pass intact through the stomach to the small intestine, where the drug is then released for absorption through the intestinal mucosa into the human body where it can exert its pharmacologic effects.
The polymers used for enteric coatings remain unionise at low pH, and therefore remain insoluble. As the pH increases in the gastrointestinal tract the acidic functional groups are capable of ionisation, and the polymer swells or becomes soluble in the intestinal fluid.
Enteric polymeric film coating allows the coated solid to pass intact through the stomach to the small intestine, where the drug is then released for absorption through the intestinal mucosa into the human body where it can exert its pharmacologic effects.
Film defects
Ø Sticking and picking
Ø Roughness
Ø Orange –peel effects
Ø Bridging and filling
Ø Blistering
Ø Hazing/Dull film
Ø Colour variation
Ø Cracking
STICKING AND PICKING
- Over wetting or excessive film thickness causes tablets to stick each other or to the coating pan.
- On drying at the point of contact, a piece of film may remain adhere to pan or tablet.
- Giving “picked” appearances to the tablet surface.
- Resulting in a small exposed area of the core.
Remedies
- Reduction in liquid application rate.
- Increase in drying air temperature and air volume.
ROUGHNESS
v A rough or gritty surface observed when the coating is applied by spray.
v Some of the droplets may dry too rapidly before reaching the tablet bed and deposits on tablet surface.
v On tablet surface spray- dried particles of finely divided droplets of coating solution.
v Surface roughness also increases with pigment concentration and polymer concentration in the coating solution.
Remedies
ü Moving the nozzle closer to the tablet bed.
ü Reducing the degree of atomization can decrease the roughness due to spray drying
ORANGE –PEEL EFFECTS
Ø Inadequate spreading of coating solution before drying causes a bumpy or Orange –peel effects On the coating.
Causes
Indicates that spresding is impaired by rapid rate of drying or by high solution viscosity.
Remedies
Thinning of coating solution with additional solvents may correct this problem.
BRIDGING AND FILLING
Ø During drying film may shrink and pull away from the sharp corners of bisect, resulting in a “Bridging” of surface dispersion.
Ø These defects can be so severe that the monogram or bisect is completely obscured.
Remedies
Increase in plasticizer contents or change in plasticizer concentration can decrease the bridging
FILLING
ü Applying too much solution, resulting in thick film, causes filling.
ü That fills and narrows the monogram or bisects.
ü In addition, if solution applied too fast, over wetting may cause the liquid to quickly fill and be retained in the monogram.
Remedies
Judicious monitoring of the fluid application rate .
Thorough mixing of tablets in the pan prevent filling.
Blistering
Ø Evaporation of solvents from the core in the oven.
Ø And effect of high temperature on the strength, elasticity and adhesion of the film may results in blistering.
Remedies
Controlled drying conditions.
Hazing/Dull film
ü Also called as bloom.
ü It can occur when too high a processing temperature is used for a particular formulation.
ü Dulling is particularly evident when cellulosic polymers are applied out of aqueous media at high processing temperature.
ü Also occur if the coated tablets are exposed to high humidity conditions and partial solvation of film results.
Colour variation
Ò Problem caused by process conditions or the formulation
Ò Improper mixing, uneven spray pattern and insufficient coating may results in colour variation.
Ò The migration of soluble dyes, plasticizer and other additives give the coating a mottled or spotted appearance.
Remedies
Ò Use of lake dyes eliminates dye migration.
Ò A reformulation with different plasticizer and additives is the best way to solve film instability.
Cracking
Ò Cracking occurs if internal stresses in the film exceed the tensile strength of the film.
Ò The tensile strength of the film can be increased by using higher molecular –weight polymers or polymer blends.
Remedies
Ò Adjusting the plasticizer types and concentration can minimize internal stresses
Ò Also adjusting the pigment types and concentration can minimize internal stresses
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