Tablet is a solid unit dosage form containing one or more active pharmaceutical ingredients. Tablets are solid, flat or biconvex discs formed by compressing a drug or a mixture of drugs with or without suitable excipients. The excipients used are diluents, disintegrants, binder or granulating agents, lubricants, glidants etc. to ensure efficient tabletting. Tablets may be swallowed whole or are dispersible or chewable. Some are administered in buccal cavity where active ingredient is released. Surgical Implants and Pessaries may also be formulated and administered in the form of tablet dosage forms. (Bare et al., 2011)
Tablet compression is very important and critical unit operation in the formulation of Tablet dosage forms. Tablets are prepared by compressing a formulation containing a mixture of drug and excipients on machines called as Presses.
1.1.1 Types of Tablets-
(A) Tablets for ingestion-
1. Compressed tablets
2. Delayed release tablets
3. Sugar coated tablets
4. Film coated tablets
5. Chewable tablets
(B) Tablet for oral cavity
1. Buccal tablets
2. Sublingual tablets
3. Compressed Lozenges
4. Dental cones
(C) Tablet administered by non-oral routes
1. Tablet Implants
2. Vaginal tablets
(D) Tablets used to prepare solution
1. Effervescent tablets
3. Hypodermic tablets
4. Tablet triturates
1.1.2 Characteristics of an ideal tablet –
1. Tablet should be elegant in appearance having its specified identity and free from organoleptic defects
2. It should have chemical and physical stability throughout the shelf life.
3. It should be capable to prevent any alteration in the chemical, physical and microbiological properties of API and formulation.
4. It should be capable of withstanding the mechanical shocks during its production, packaging, shipping and dispensing.
5. An ideal tablet should be able to release the API in body in predictable and reproducible manner.
1.1.3 Advantages of Tablets-
1. Accuracy of dose is maintained as it is a solid unit dosage form.
2. The release profile can be programmed by using the different types of excipients and other formulation related variables.
3. Large scale manufacturing is easier and reproducible in comparison to the other solid unit dosage forms
4. Less chances of microbial growth due to less moisture content leads to longer shelf life.
5. Strict environmental control is not required as it is a non-sterile dosage form.
6. Ease of packaging over liquid dosage form.
7. Organoleptic masking can be improved by coating the tablets and easy product identification.
8. Ease of administration and also self administration.
9. Tamper proof in comparison to Capsules.
1.1.4 Disadvantages of Tablets-
1. Difficult to formulate tablet of suitable size in case of high dose drugs with low compressibility.
2. Difficult to swallow for pediatric and geriatric patients.
3. Cannot be administered to unconscious patients.
4. Onset of action is slower in comparison to other dosage forms.
5. Liquid drugs are difficult to formulate as tablets.
1.1.5 Excipients-
Pharmaceutical excipients are defined as the component of formulation other than API that had been appropriately evaluated for safety and had specific function in formulation –
1. Aid processing during the manufacturing process.
2. Enhance stability, bioavailability or patient acceptability.
3. Enhance safety and efficacy of the product throughout the shelf life.
4. Assist in the easy identification of the product. (Lachman et al.1991)
The excipients are classified as-
A. Primary excipients- They comprises the major bulk of a formulation.
Example- Diluents, Disintegrants, Binders.
B. Secondary excipients 'They include the components which are responsible for the appearance and performance.
Example – Film coating, Colors, Flavors, and Sweeteners.
1. Diluents ' They are added to the tablet formulation to facilitate tablet handling during manufacturing and also to provide better tablet properties such as- Improved cohesion, facilitate direct compression manufacturing, to enhance flow ability, to adjust the weight of the tablet as per die capacity.
Example ' Starch, Microcrystalline cellulose, Lactose, Calcium phosphate, etc.
2. Binders ' They promote cohesiveness for converting powders into granules by a process known as granulation which is a unit operation by which powdery materials are agglomerated into larger entity called granules.
Example ' Partially pre gelatinized starch, Hydroxy Propyl Methyl Cellulose, Polyvinylpyrollidone, Sodium carboxymethyl cellulose, etc.
3. Disintegrants ' They are added to the tablet formulation to promote the desegregation of a tablet when it comes in contact with the aqueous medium before the dissolution occurs. The objective behind the disintegration process is to increase surface area of the tablet granule by overcoming the cohesive fragments to speed up the rate of dissolution.
Example ' Starch, Sodium starch glycolate, Pregelatinized starch, etc.
4. Lubricants ' These agents acts by reducing friction between the tablet surface and the die wall during compression and ejection.
Example ' Magnesium stearate, Calcium stearate, Talc, Waxes, etc.
5. Glidants ' These are added to the formulation to improve the flow property of the material which is to be fed to the die cavity and in particle rearrangement during compression.
Example ' Colloidal silica, Hydrated sodium silioaluminate, etc.
6. Miscellaneous excipients '
i. Wetting agents ' They aid in water uptake in contact with medium and promote disintegration and dissolution. It is mainly added when hydrophobic drugs are formulated.
Example ' Anionic surfactants like Sodium Lauryl Sulfate, Sodium diisobutylsulfosuccinate, etc.
ii. Dissolution retardants ' They are used in formulation when the controlled or delayed release of the drug is intended.
Example ' Waxy materials like stearic acid and their stearates, etc.
iii. Adsorbents ' These are the agents that can retain the large quantities of fluids in the formulation. These are particularly useful in formulating liquid drugs like Vitamin E.
Example ' Silicon Dioxide, Bentonite, Kaolin, Magnesium carbonate, etc.
iv. Buffers- They are added to the formulation to maintain the pH of the formulation and thereby enhances the stability.
Example ' Sodium bicarbonate, Sodium citrate, Sodium carbonate, etc.
v. Antioxidants ' These agents gets preferentially oxidized in place of drug and thus prevents oxidation degradation of the formulation. They may also acts as synergism to other antioxidants.
Example – Sodium bisulfite, Sodium metabisulfite, alpha Tocopherol, etc.
vi. Chelating agents 'These agents forms chelates with the heavy metal ions which forms complex with the medicaments causing the oxidative or ionic degradation of drugs.
Example ' Ethylene diamine tetra acetic acid, Citric acid, Tartaric acid, etc.
vii. Preservatives ' They are added to the formulation to prevent the growth of micro-organism in the formulation throughout the shelf life during storage and use.
Example ' Methyl paraben, Propyl paraben, Benzyl, etc.
viii. Colorants ' The two forms of colors are used '
Dyes – These are available as solutions and are applied as such during granulation.
Lakes ' These are dyes adsorbed on hydrous oxides and are employed as dry powders.
Example- Sunset Yellow, Tartrazine, Eosin Y.
ix. Flavouring and Sweetening agents '
They are used to improve the taste of chewable tablets as well as the mouth dissolving tablets.
Example ' Vaniline, Sugar, Mannitol, Saccharine, etc.
1.1.6 GRANULATION-
It is the process of size enlargement where the small powdered particles are agglomerated to convert them to free flowing state. Size enlargement is achieved by agglomeration by some method of agitation in the mixing equipment or by Compaction, extrusion or pelletization. (George et al.1999)
The purpose for granulation are'
1. To densify the material
2. To improve the flow property.
3. Improve the compression characteristics.
4. To perform uniform mixtures.
5. To obtain the desired release profile.
6. Reduction in dust and fines.
7. Improve the appearance of tablets.
The different types of granulation process are –
1.1.6.1 Wet Granulation '
It is a process in which the liquid binder is added to the vessel equipped with agitator that will produce the granules. The preliminary step is particle size reduction which is achieved using a variety of mills or grinders.
The next step is powder mixing which is achieved using a blender with tumbling or convective mechanism. The addition of the liquid binder to produce a wet mass utilizes equipment with strong kneading action such as sigma or planetary mixer. The wet mass is formed into granules by forcing through a perforated steel plate or through a oscillating granulator. The granules are then dried in tray drier or FBD followed by dry screening. The granules are then transferred for final mixing for final lubrication.
1.1.6.2 Dry Granulation '
The granulation takes place in absence of any solvent where high stress is applied over the powders to bring about the agglomeration.
The methods by which the granules are formed are of two types-
1. Slugging '
In this method, the excipients and the API are mixed and compressed into over size tablets called slugs using a heavy duty tabletting press which is capable of applying a high stress. The compact prepared in such a manner is termed as 'slug'. The process is followed by the milling and sizing of the granules to the required size.
2. Roller Compaction '
The powdered excipients and the drug are mixed and are then compressed using roller compactor. The powder are fed from the hopper to the moving belt and forcefully passed through the narrow gap between two oppositely moving rollers to produce a sheet of compressed material. The compressed sheet is then milled and sized to obtain the granules of the desired size.
1.1.6.3 Direct Compression '
The process involves the powder mixing followed by the compression of the powder mix without the need for granulation. The process involves the three basic steps '
1. Size reduction of drugs and excipients.
2. Blending of excipients.
3. Tablet compression.