A tablet is a mixture of active substances and excipients, usually in powder form, pressed or compacted into a solid. The excipients include 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. Tablet formation represents the last stage in down-stream processing within the pharmaceutical industry. It is just one of the many forms that an oral drug can take such as syrups, elixirs, suspensions, and emulsions. It consists of an active pharmaceutical ingredient (A.P.I.) with biologically inert excipients in a compressed, solid form.
Medicinal tablets were originally made in the shape of a disk of whatever color their components determined, but are now made in many shapes and colors to help users to distinguish between different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".
Medicines to be taken orally are very often supplied in tablet form; indeed the word tablet without qualification would be taken to refer to a medicinal tablet. Medicinal tablets and capsules are often called pills. Other products are manufactured in the form of tablets which are designed to dissolve or disintegrate; e.g. cleaning and deodorizing products.
In the tablet-pressing process, it is important that all ingredients be fairly dry, powdered or granular, somewhat uniform in particle size, and freely flowing. Mixed particle sized powders can segregate due to operational vibrations, which can result in tablets with poor drug or active pharmaceutical ingredient (API) content uniformity. Content uniformity ensures that the same API dose is delivered with each tablet.
Some APIs may be tableted as pure substances, but this is rarely the case; most formulations include excipients. Normally, an inactive ingredient (excipient) termed a binder is added to help hold the tablet together and give it strength. A wide variety of binders may be used, some common ones including lactose powder, dibasic calcium phosphate, sucrose, corn (maize) starch, microcrystalline cellulose and modified cellulose (for example hydroxymethyl cellulose).
Often, an ingredient is also needed to act as a disintegrant that hydrates readily in water to aid tablet dispersion once swallowed, releasing the API for absorption. Some binders, such as starch and cellulose, are also excellent disintegrants.
Small amounts of lubricants are usually added, as well. The most common of these is magnesium stearate; however, other commonly used tablet lubricants include stearic acid (stearin), hydrogenated oil, and sodium stearyl fumarate. These help the tablets, once pressed, to be more easily ejected from the die.
Friability is an important factor in tablet formulation to ensure that the tablet can stay intact and withhold its form from any outside force of pressure:
Friability below 0.8% is usually considered satisfactory.
Tablets are easy and convenient to use. They provide an accurately measured dosage in a convenient portable package, and can be designed to protect unstable medications or disguise unpalatable ingredients. Coatings can be coloured or stamped to aid tablet recognition. Manufacturing processes and techniques can provide tablets special properties; for example enteric coatings or sustained release formulations.
Tablets cannot be used adequately in case of emergency cases. This is because the rate at which the active ingredient reaches the site to be treated is slow. Other means such intravenous and intramuscular injections are more effective. 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. Some drugs may be deactivated by the liver (the "first pass effect") making them unsuitable for oral use. Drugs which can be taken sublingually bypass the liver and are less susceptible to the first pass effect. Bioavailability of some drugs may be low due to poor absorption from the gastric tract. Such drugs may need to be given in very high doses or by injection. For drugs that need to have rapid onset, or that have severe side effects, the oral route may not be suitable. For example Salbutamol, used to treat problems in the pulmonary system, can have effects on the heart and circulation if taken orally; these effects are greatly reduced by inhaling smaller doses direct to the required site of action.
Tablet diameter and shape are determined a combination of a set of punches and a die. This is called a station of tooling. The thickness is determined by the amount of tablet material and the position of the punches in relation to each other during compression. Once this is done, we can measure the corresponding pressure applied during compression. The shorter the distance between the punches, thickness, the greater the pressure applied during compression, and sometimes the harder the tablet. Tablets need to be hard enough that they don't break up in the bottle, yet friable enough that they disintegrate in the gastric tract.
The tablet is composed of the Active Pharmaceutical Ingredient (that is the active drug) together with various excipients. These are biologically inert ingredients which either enhance the therapeutic effect or are necessary to construct the tablet. The filler or diluent (e.g. lactose or sorbitol)is a bulking agent, providing a quantity of material which can accurately be formed into a tablet. Binders (e.g. methyl cellulose or gelatin) hold the ingredients together so that they can form a tablet. Lubricants (e.g. magnesium stearate or polyethylene glycol) are added to reduce the friction between the tablet and the punches and dies so that the tablet compression and ejection processes are smooth. Disintegrants (e.g. starch or cellulose) are used to promote wetting and swelling of the tablet so that it breaks up in the gastro intestinal tract; this is necessary to ensure dissolution of the API. Superdisintegrants are sometimes used to greatly speed up the disintegration of the tablet. Additional ingredients may also be added such as coloring agents, flavoring agents, and coating agents. Formulations are designed using small quantities in a laboratory machine called a Powder Compaction Simulator. This can prove the manufacturing process and provide information for the regulatory authorities.
Powders that can be mixed well do not require granulation and can be compressed into tablets through Direct Compression
Granulation is the process of collecting particles together by creating bonds between them. There are several different methods of granulation. The most popular, which is used by over 70% of formulation in tablet manufacture is wet granulation. Dry granulation is another method used to form granules.
Water may be used as the liquid binder, but sometimes many actives are not compatible with water. Water mixed into the powder can form bonds between powder particles that are strong enough to lock them in together. However, once the water dries, the powders may fall apart and therefore might not be strong enough to create and hold a bond. Povidone also known as polyvinyl pyrrolidone (PVP) is one of the most commonly used pharmaceutical binders. PVP and a solvent are mixed with the powders to form a bond during the process, and the solvent evaporates. Once the solvent evaporates and powders have formed a densely held mass, then the granulation is milled which results in formation of granules
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.
Initial quantities of active pharmaceutical ingredients are very expensive to produce, and using a Compaction Simulator reduces the amount of powder required for development.
Load controlled tests are particularly useful for designing multi-layer tablets where layer interface conditions must be studied.
Test data recorded by the Simulators must meet the regulations for security, completeness and quality to support new or modified drug filings, and show that the designed manufacturing process is robust and reliable.
If the active ingredient of a tablet is sensitive to acid, or is irritant to the stomach lining, an enteric coating can be used, which is resistant to stomach acid and dissolves in the high pH of the intestines. Enteric coatings are also used for medicines that can be negatively affected by taking a long time to reach the small intestine where they are absorbed. Coatings are often chosen to control the rate of dissolution of the drug in the gastro-intestinal tract. Some drugs will be absorbed better at different points in the digestive system. If the highest percentage of absorption of a drug takes place in the stomach, a coating that dissolves quickly and easily in acid will be selected. If the rate of absorption is best in the large intestine or colon, then a coating that is acid resistant and dissolves slowly would be used to ensure it reached that point before dispersing. The area of the gastro-intestinal tract with the best absorption for any particular drug is usually determined by clinical trials.
This is the last stage in tablet formulation and it is done to protect the tablet from temperature and humidity constraints. It is also done to mask the taste, give it special characteristics, distinction to the product, and prevent inadvertent contact with the drug substance. The most common forms of tablet coating are sugar coating and film coating.
Coating is also performed for the following reasons:
Sugar coating is done by rolling the tablets in heavy syrup, in a similar process to candy making. It is done to give tablets an attractive appearance and to make pill-taking less unpleasant. However, the process is tedious and time-consuming and it requires the expertise of highly skilled technician. It also adds a substantial amount of weight to the tablet which can create some problems in packaging and distribution.
In comparison to sugar coating, film coating is more durable, less bulky, and less time consuming. But it creates more difficulty in hiding tablet appearance. One application of film-coating is for enteric protection, termed enteric coating. The purpose of enteric coating is to prevent dissolution of the tablet in the stomach, where the stomach acid may degrade the active ingredient, or where the time of passage may compromise its effectiveness, in favor of dissolution in the small intestine, where the active principle is better absorbed.
Tablet presses, also called tableting machines, range from small, inexpensive bench-top models that make one tablet at a time (single-station presses), no more than a few thousand an hour, and with only around a half-ton pressure, to large, computerized, industrial models (multi-station rotary or eccentric presses) that can make hundreds of thousands to millions of tablets an hour with much greater pressure. Some tablet presses can make extremely large tablets, such as some of the toilet cleaning and deodorizing products or dishwasher soap. Others can make smaller tablets, from regular aspirin to some the size of a bb gun pellet. Tablet presses may also be used to form tablets out of a wide variety of materials, from powdered metals to cookie crumbs. The tablet press is an essential piece of machinery for any pharmaceutical and nutraceutical manufacturer.
It is sometimes necessary to split tablets into halves or quarters. Tablets are easier to break accurately if scored, but there are devices called pill-splitters which cut unscored and scored tablets. Tablets with special coatings (for example enteric coatings or controlled-release coatings) should not be broken before use, as this will expose the tablet core to the digestive juices, short-circuiting the intended delayed-release effect.