Tabletsby Sreejith t.s : Tabletsby Sreejith t.s Slide 2: Introduction Solid medicaments may be administered orally as powders, pills, cachets, capsules or tablets .These dosage forms contain a quantity of drug which is given as a single unit and they are known collectively as solid unit dosage forms, even in the case of sustained action preparations which, technically, contain the equivalent of several normal doses of drug .The stringent formulation requirements of modern medicaments, the many advantages of tablet and capsule medication, coupled with expanding health services and the commitment need for large-scale economic manufacture, have led to a steady decline in the prescribing of powders and pills .Tablets and capsules, on the other hand, currently account for well over two third of the total number and cost of medicines produced all over the world.
Tablet is defined as a compressed solid dosage form containing medicaments with or without excipients. According to the Indian Pharmacopoeia Pharmaceutical tablets are solid, flat or biconvex dishes, unit dosage form, prepared by compressing a drugs or a mixture of drugs, with or without diluents. They vary in shape and differ greatly in size and weight, depending on amount of medicinal substances and the intended mode of administration. It is the most popular dosage form and 70% of the total medicines are dispensed in the form of Tablet. All medicaments are available in the Tablet form except where it is difficult to formulate or administer. Slide 3: The advantages of the Tablet dosage form are:
1. They are 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 enteric 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. Slide 4: Disadvantages of Tablet dosage form are:
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, optimum absorption high in GIT may be difficult to formulate or manufacture as a tablet that will still provide adequate or full drug bioavailability.
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 Slide 5: 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. Slide 6: Different types of Tablets
(A) Tablets ingested orally:
1. Compressed tablet, e.g. Paracetamol tablet
2. Multiple compressed tablet
3. Repeat action tablet
4. Delayed release tablet, e.g. Enteric coated 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 Slide 7: (c) Tablets administered by other route:
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) Slide 8: Tablet Ingredients
In addition to active ingredients, tablet contains a number of inert materials known as additives or excipients. Different excipients are:
2. Binder and adhesive
4. Lubricants and glidants
5. Colouring agents
6. Flavoring agents
7. Sweetening agents Slide 9: 1. Diluent: 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. A diluent should have following properties:
1. They must be non toxic
2. They must be commercially available in acceptable grade
3. There cost must be low
4. They must be physiologically inert
5. They must be physically & chemically stable by themselves & in combination with the drugs.
6. They must be free from all microbial contamination.
7. They do not alter the bioavailability of drug.
8. They must be color compatible. Slide 10: Commonly used tablet diluents
1. Lactose-anhydrous and spray dried lactose
2. Directly compressed starch-Sta Rx 1500
3. Hydrolyzed starch-Emdex and Celutab
4. Microcrystalline cellulose-Avicel (PH 101and PH 102)
5. Dibasic calcium phosphate dehydrate
6. Calcium sulphate dihydrate
9. Sucrose- Sugartab, DiPac, Nutab
10. Dextrose Slide 11: 2. Binders and Adhesives: These materials are added either dry or in wet- form to form granules or to form cohesive compacts for directly compressed tablet.
Example: Acacia, tragacanth- Solution for 10-25% Conc.
Cellulose derivatives- Methyl cellulose, Hydroxy propyl methyl
cellulose, Hydroxy propyl cellulose
Gelatin- 10-20% solution
Glucose- 50% solution
Polyvinylpyrrolidone (PVP)- 2% conc.
Starch paste-10-20% solution
Sorbitol 3. Disintegrants: Added to a tablet formulation to facilitate its breaking or disintegration when it contact in water in the GIT.
Example: Starch- 5-20% of tablet weight.
Starch derivative – Primogel and Explotab (1-8%)
Clays- Veegum HV, bentonite 10% level in colored tablet only
Cellulose derivatives- Ac- Di-Sol (sodium carboxy methyl
PVP (Polyvinylpyrrolidone), cross-linked Slide 12: Superdisintegrants: Swells up to ten fold within 30 seconds when contact water.
Example: Crosscarmellose- cross-linked cellulose, Crosspovidone- cross-linked povidone (polymer), Sodium starch glycolate- cross-linked starch. These cross-linked products swell upto 10n fold with in 30 seconds when in contact with water.
A portion of disintegrant is added before granulation and a portion before compression, which serve as glidants or lubricant. Evaluation of carbon dioxide in effervescent tablets is also one way of disintegration
4. Lubricant and Glidants: Lubricants are intended to prevent adhesion of the tablet materials to the surface of dies and punches, reduce inter particle friction and may improve the rate of flow of the tablet granulation.
Glidants are intended to promote flow of granules or powder material by reducing the friction between the particles.
Example: Lubricants- Stearic acid, Stearic acid salt - Stearic acid, Magnesium stearate, Talc, PEG (Polyethylene glycols), Surfactants
Glidants- Corn Starch – 5-10% conc., Talc-5% conc., Silica derivative - Colloidal silicas such as Cab-O-Sil, Syloid, Aerosil in 0.25-3% conc. Slide 13: 5. 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 Slide 14: 6. Flavoring agents: For chewable tablet- flavor oil are used
7. Sweetening agents: For chewable tablets: Sugar, mannitol.
Saccharine (artificial): 500 time’s sweeter than sucrose
Disadvantage: Bitter aftertaste and carcinogenic
Disadvantage: Lack of stability in presence of moisture. Slide 15: Granulation technology on large scale by various techniques Slide 16: Tablet Compression Machine
Tablets are made by compressing a formulation containing a drug or drugs with excipients on stamping machine called presses. Tablet presses are designed with following basic components:
1) Hopper for holding and feeding granulation
2) Dies that define the size and shape of the tablet.
3) Punches for compressing the granulation within the dies.
4) Cam tracks for guiding the movement of the punches.
5) A feeding mechanism for moving granulation from hopper into the
dies Slide 18: Evaluation of Tablet
1. General Appearance: The general appearance of a tablet, its identity and general elegance is essential for consumer acceptance, for control of lot-to-lot uniformity and tablet-to-tablet uniformity. The control of general appearance involves the measurement of size, shape, color, presence or absence of odor, taste etc.
2. Size & Shape: It can be dimensionally described & controlled. The thickness of a tablet is only variables. Tablet thickness can be measured by micrometer or by other device. Tablet thickness should be controlled within a ± 5% variation of standard value.
3. 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.
4. Organoleptic properties: Color distribution must be uniform with no mottling. For visual color comparison compare the color of sample against standard color.
5. Hardness and Friability: Tablet requires a certain amount of strength or hardness and resistance to friability to withstand mechanical shakes of handling in manufacture, packaging and shipping. Hardness generally measures the tablet crushing strength Slide 19: 6.Friability: Friability of a tablet can determine in laboratory by Roche friabilator. This consist of a plastic chamber that revolves at 25 rpm, dropping the tablets through a Distance of six inches in the friabilator, which is then operate for 100 revolutions. The tablets are reweighed. Compress tablet that lose less than 0.5 to 1.0 % of the Tablet weigh are consider acceptable. Slide 20: 2. Drug Content and Release: (I) Weight Variation test (U.S.P.): Take 20 tablet and weighed individually. Calculate average weight and compare the individual tablet weight to the average. The tablet pass the U.S.P. 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.
(II) Content Uniformity Test: Randomly select 30 tablets. 10 of these assayed individually. The Tablet pass the test if 9 of the 10 tablets must contain not less than 85% and not more than 115% of the labeled drug content and the 10th tablet may not contain less than 75% and more than 125% of the labeled content. If these conditions are not met, remaining 20 tablet assayed individually and none may fall out side of the 85 to 115% range.
(III) Disintegration Test (U.S.P.): The U.S.P. device to test disintegration uses 6 glass tubes that are 3” long; open at the top and 10 mesh screen at the bottom end. To test for disintegration time, one tablet is placed in each tube and the basket rack is positioned in a 1-L beaker of water, simulated gastric fluid or simulated intestinal fluid at 37 ± 20 C such that the tablet remain 2.5 cm below the surface of liquid on their upward movement and not closer than 2.5 cm from the bottom of the beaker in their downward movement. 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.
According to the test the tablet must disintegrate and all particles must pass through the 10 mesh screen in the time specified. If any residue remains, it must have a soft mass.
Disintegration time: Uncoated tablet: 5-30 minutes
Coated tablet: 1-2 hours Slide 22: 3.Dissolution Test (U.S.P.): Two set of apparatus:
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 100 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 to determine the amount of drug in solutions.
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. For dissolution test U.S.P. specifies the dissolution test medium and volume, type of apparatus to be used, rpm of the shaft, time limit of the test and assay procedure for. The test tolerance is expressed as a % of the labeled amount of drug dissolved in the time limit. Slide 24: Tablet Coating
Tablet coatings perform one or more of the following functions. They may: mask the taste of unpalatable drugs, protect the drug from deterioration due to light, oxygen or moisture, separate incompatible ingredients, control the release of medicament in the gastrointestinal tract, and provide an elegant or distinctive finish to the tablet.
The materials used for coating may largely comprise sucrose (sugar coating), water-soluble film-forming polymers (film coating) or substances which are soluble in the intestinal secretions but not in those of the stomach (enteric coating). These types of coating can all be applied by the pan or fluid-bed processes; the compression coating technique is suitable for sugar and enteric coatings, but not for film coating.
Types of Coating
Different coating processes are: Pan coating, Fluid Bed Coating, Compression coating
Pan Coating Slide 26: B. Fluid-Bed Coating Slide 27: Compression Coating Machines Slide 28: Other methods of coating equipments:
Perforated Pan Systems
Accela-Cota: It is a prototype of perforated cylindrical drum providing high drying air capacity. Therefofe it is preferred for film coating. Slide 29: Hi-coater system: The drying air is directed into the drum is passed through the tablet bed, and is exhausted through the perforations in the drum. Slide 30: SUPERCELL™ Tablet Coater
Revolutionary tablet coater that accurately deposits controlled amounts of coating materials on tablets, even if they are extremely hygroscopic or friable. Slide 31: Problems in tableting 1 Capping
2 Lamination / Laminating
5 Sticking / Filming
9 Double impression Slide 32: 1 Blistering
8 Colour variation
10 Orange peel/Roughness
11 Cracking/Splitting Problems and remedies for tablet coating Slide 33: THE CAUSES AND REMEDIES OF CAPPING RELATED TO ‘FORMULATION’ (GRANULATION) Slide 34: THE CAUSES AND REMEDIES OF CAPPING RELATED TO ‘MACHINE’ (DIES, PUNCHES AND TABLET PRESS) Slide 35: The Causes and Remedies of Lamination related to MACHINE (Dies, Punches and Tablet Press)] THE CAUSES AND REMEDIES OF CHIPPING RELATED TO FORMULATION (GRANULATION) ARE AS FOLLOWS Slide 36: THE CAUSES AND REMEDIES OF CHIPPING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS) THE CAUSES AND REMEDIES OF CRACKING RELATED TO FORMULATION (GRANULATION) Slide 37: THE CAUSES AND REMEDIES OF CRACKING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS) THE CAUSES AND REMEDIES OF STICKING RELATED TO FORMULATION (GRANULATION) Slide 38: THE CAUSES AND REMEDIES OF STICKING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS) THE CAUSES AND REMEDIES OF PICKING RELATED TO FORMULATION (GRANULATION) Slide 39: THE CAUSES AND REMEDIES OF PICKING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS) THE CAUSES AND REMEDIES OF BINDING RELATED TO FORMULATION (GRANULATION) Slide 40: THE CAUSES AND REMEDIES OF BINDING RELATED TO MACHINE (DIES, PUNCHES AND TABLET PRESS) THE CAUSES AND REMEDIES OF MOTTLING Slide 41: PROBLEMS AND REMEDIES FOR TABLET COATING Thank ‘u’ : Thank ‘u’