An
excipient is an inactive substance used as a carrier for the
active ingredientAn active ingredient , is the substance in a drug or a pesticide that is pesticidal or pharmaceutically active. Terms in similar use include: active pharmaceutical ingredient and bulk active in medicine, or in pesticide formulations active substance may be used. Some medications and pesticide...
s of a
medicationA pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
. In many cases, an "active" substance (such as
aspirinAspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication....
) may not be easily administered and absorbed by the human body; in such cases the substance in question may be dissolved into or mixed with an excipient. Excipients are also sometimes used to bulk up formulations that contain very potent active ingredients, to allow for convenient and accurate dosage. In addition to their use in the single-dosage quantity, excipients can be used in the manufacturing process to aid in the handling of the active substance concerned. Depending on the
route of administrationA route of administration in pharmacology and toxicology is the path by which a drug, fluid, poison, or other substance is brought into contact with the body....
, and form of medication, different excipients may be used. For oral administration
tabletA tablet is a mixture of active substances and excipients, usually in powder form, pressed or compacted into a solid. The excipients include binders, glidants and lubricants to ensure efficient tabletting; disintegrants to ensure that the tablet breaks up in the digestive tract; sweeteners or...
s and
capsuleThe word capsule, or encapsulation, may refer to:* Capsule , a cover or envelope partly or wholly surrounding a structure.* Capsule , a type of dry fruit like the poppy, iris or foxglove...
s are used.
SuppositoriesA suppository is a drug delivery system that is inserted into the rectum , vagina , or urethra , where it dissolves....
are used for rectal administration.
Often, once an active ingredient has been purified, it cannot stay in purified form for long. In many cases it will denature, fall out of solution, or stick to the sides of the container. To stabilize the active ingredient, excipients are added, ensuring that the active ingredient stays "active", and, just as importantly, stable for a sufficiently long period of time that the shelf-life of the product makes it competitive with other products. Thus, the formulation of excipients in many cases is considered a
trade secretA trade secret is a formula, practice, process, design, instrument, pattern, or compilation of information which is not generally known or reasonably ascertainable, by which a business can obtain an economic advantage over competitors or customers...
.
Pharmaceutical codes require that all ingredients in drugs, as well as their
chemical decompositionChemical decomposition or analysis is the separation of a chemical compound into elements or smaller compounds. It is sometimes defined as the opposite of a chemical synthesis. Chemical decomposition is often an undesired chemical reaction...
products are identified and guaranteed to be safe. For this reason, excipients are only used when absolutely necessary and in the smallest amounts possible.
Antiadherents
Antiadherents are used to reduce the
adhesionAdhesion is the tendency of certain dissimilar molecules to cling together due to attractive forces.-Mechanisms of adhesion:Five mechanisms have been proposed to explain why one material sticks to another:-Mechanical adhesion:...
between the
powderA powder is a dry, bulk solid composed of a large number of very fine particles that may flow freely when shaken or tilted. Powders are a special sub-class of granular materials, although the terms powder and granular are sometimes used to distinguish separate classes of material...
(
granuleGranule is a generic term used for a small particle or grain. The generic term is used in a variety of specific contexts.* Granule , visible structures in the photosphere of the Sun arising from activity in the Sun's convective zone...
s) and the punch faces and thus prevent sticking to tablet punches.
Most commonly used is
magnesium stearateMagnesium stearate, also called octadecanoic acid, magnesium salt, is a white substance which is solid at room temperature. It has the chemical formula Mg2. It is a salt containing two equivalents of stearate and one magnesium cation...
.
Binders
Binders hold the ingredients in a tablet together.
Binders ensure that tablets and granules can be formed with required mechanical strength, and give volume to low active dosis tablets. Binders are usually
starchStarch or amylum is a polysaccharide carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds.Starch is produced by all green plants as an energy store and is a major food source for humans....
es,
sugarSugar is a class of edible crystalline substances, mainly sucrose, lactose, and fructose. Human taste buds interpret its flavor as sweet. Sugar as a basic food carbohydrate primarily comes from sugar cane and from sugar beet, but also appears in fruit, honey, sorghum, sugar maple , and in many...
s,
celluloseCellulose is an organic compound with the formula , a polysaccharide consisting of a linear chain of several hundred to over ten thousand β linked D-glucose units....
or modified cellulose such as microcrystalline cellulose,
hydroxypropyl celluloseHydroxypropyl cellulose is a derivative of cellulose with both water solubility and organic solubility. It is used as a topical ophthalmic protectant and lubricant.-Chemistry:...
,
lactoseLactose is a sugar that is found most notably in milk. Lactose makes up around 2–8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey...
, or sugar alcohols like
xylitolXylitol is an organic compound with the formula
32. This achiral species is one of four isomers of 1,2,3,4,5-pentapentanol...
,
sorbitolSorbitol, also known as glucitol, is a sugar alcohol that the human body metabolises slowly. It is obtained by reduction of glucose changing the aldehyde group to an additional hydroxyl group.-Sweetener:...
or
maltitolMaltitol is a sugar alcohol used as a sugar substitute. It has 75-90% of the sweetness of sucrose and nearly identical properties, except for browning. It is used to replace table sugar because it has fewer calories, does not promote tooth decay and has a somewhat lesser effect on blood glucose...
.
Binders are classified according to their application:
- Solution binders are dissolved in a solvent (for example water
Water is an ubiquitous chemical substance that is composed of hydrogen and oxygen and is essential for all known forms of life.In typical usage, water refers only to its liquid form or state, but the substance also has a solid state, ice, and a gaseous state, water vapor or steam. Water covers 71%...
or alcoholEthanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug, best known as the type of alcohol found in alcoholic beverages and in modern thermometers. Ethanol is one of the oldest recreational drugs...
can be used in wet granulation processes). Examples include gelatinGelatin is a translucent, colorless, odorless, brittle, nearly tasteless solid substance, derived from the collagen inside animals' skin and bones. It is commonly used as a gelling agent in food, pharmaceuticals, photography, and cosmetic manufacturing. Substances containing gelatin or functioning...
, celluloseCellulose is an organic compound with the formula , a polysaccharide consisting of a linear chain of several hundred to over ten thousand β linked D-glucose units....
, cellulose derivatives, polyvinylpyrrolidone, starchStarch or amylum is a polysaccharide carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds.Starch is produced by all green plants as an energy store and is a major food source for humans....
, sucroseSucrose, commonly called table sugar, is a moosaccharide of glucose and fructose with the molecular formula C12H22O11. This white, odorless, crystalline powder has a pleasing, sweet taste. It is best known for its role in human nutrition...
and polyethylene glycolPoly , also known as poly , polyoxyethylene and under the tradename Carbowax is the most commercially important type of polyether. PEG, PEO or POE refers to an oligomer or polymer of ethylene oxide...
.
- Dry binders are added to the powder blend, either after a wet granulation step, or as part of a direct powder compression (DC) formula. Examples include cellulose
Cellulose is an organic compound with the formula , a polysaccharide consisting of a linear chain of several hundred to over ten thousand β linked D-glucose units....
, methyl cellulose, polyvinylpyrrolidone, and polyethylene glycolPoly , also known as poly , polyoxyethylene and under the tradename Carbowax is the most commercially important type of polyether. PEG, PEO or POE refers to an oligomer or polymer of ethylene oxide...
.
Coatings
Tablet coatings protect tablet ingredients from deterioration by moisture in the air and make large or unpleasant-tasting tablets easier to swallow. For most coated tablets, a hydroxy propylmethylcellulose (HPMC) film coating is used which is free of sugar and potential
allergenAn allergen is a nonparasitic antigen capable of stimulating a type-I hypersensitivity reaction in atopic individuals.Most humans mount significant Immunoglobulin E responses only as a defense against parasitic infections. However, some individuals mount an IgE response against common...
s. Occasionally, other coating materials are used, for example synthetic polymers,
shellacShellac is a resin secreted by the female lac bug to form a cocoon, on trees in the forests of India and Thailand. It is processed and sold as dry flakes , which are dissolved in denatured alcohol to make liquid shellac, which is used as a brush-on colorant, food glaze and wood finish much like a...
, corn protein
zeinZein is a class of prolamine protein found in maize. It is usually manufactured as a powder from corn gluten meal.Zein is one of the most well understood plant proteins and has a variety of industrial and food uses...
or other
polysaccharidePolysaccharides are polymeric carbohydrate structures, formed of repeating units joined together by glycosidic bonds. These structures are often linear, but may contain various degrees of branching. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit...
s.
CapsuleThe word capsule, or encapsulation, may refer to:* Capsule , a cover or envelope partly or wholly surrounding a structure.* Capsule , a type of dry fruit like the poppy, iris or foxglove...
s are coated with
gelatinGelatin is a translucent, colorless, odorless, brittle, nearly tasteless solid substance, derived from the collagen inside animals' skin and bones. It is commonly used as a gelling agent in food, pharmaceuticals, photography, and cosmetic manufacturing. Substances containing gelatin or functioning...
.
Changing the dissolution rates of active species
Enteric coatingAn enteric coating is a barrier applied to oral medication that controls the location in the digestive system where it is absorbed. Enteric refers to the small intestine, therefore enteric coatings prevent release of medication before it reaches the small intestine.Most enteric coatings work by...
s control the rate of drug release and determine where the drug will be released in the digestive tract.
Disintegrants
Disintegrants expand and dissolve when wet causing the tablet to break apart in the digestive tract, releasing the active ingredients for absorption. Disintegrant types include:
- Water uptake facilitators
- Tablet rupture promoters
They ensure that when the tablet is in contact with
waterWater is an ubiquitous chemical substance that is composed of hydrogen and oxygen and is essential for all known forms of life.In typical usage, water refers only to its liquid form or state, but the substance also has a solid state, ice, and a gaseous state, water vapor or steam. Water covers 71%...
, it rapidly breaks down into smaller fragments, thereby facilitating
dissolutionSolvation, also sometimes called dissolution, is the process of attraction and association of molecules of a solvent with molecules or ions of a solute...
.
Examples of disintegrants include: crosslinked
polyvinyl pyrrolidonePolyvinylpyrrolidone is a water-soluble polymer made from the monomer N-vinylpyrrolidone:Polyvinylpolypyrrolidone is a highly cross-linked modification of PVP.-Properties:...
, sodium starch glycolate, crosslinked sodium carboxymethyl cellulose (crosscarmellose).
Fillers and diluents
Fillers fill out the size of a tablet or capsule, making it practical to produce and convenient for the consumer to use. By increasing the bulk volume, the fillers make it possible for the final product to have the proper volume for patient handling.
A good filler must be inert, compatible with the other components of the formulation, non-hygroscopic, soluble, relatively cheap, compactible, and preferably tasteless or pleasant tasting.
Plant
celluloseCellulose is an organic compound with the formula , a polysaccharide consisting of a linear chain of several hundred to over ten thousand β linked D-glucose units....
(pure plant filler) is a popular filler in tablets or hard
gelatinGelatin is a translucent, colorless, odorless, brittle, nearly tasteless solid substance, derived from the collagen inside animals' skin and bones. It is commonly used as a gelling agent in food, pharmaceuticals, photography, and cosmetic manufacturing. Substances containing gelatin or functioning...
capsules. Dibasic
calcium phosphateCalcium phosphate is the name given to a family of minerals containing calcium ions together with orthophosphates , metaphosphates or pyrophosphates and occasionally hydrogen or hydroxide ions.It is the principal form of calcium found in bovine milk...
is another popular tablet filler. A range of
vegetable fats and oilsVegetable fats and oils are lipid materials derived from plants. Physically, oils are liquid at room temperature, and fats are solid. Chemically, both fats and oils are composed of triglycerides, as contrasted with waxes which lack glycerin in their structure...
can be used in soft gelatin capsules.
Other examples of fillers include:
lactoseLactose is a sugar that is found most notably in milk. Lactose makes up around 2–8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey...
,
sucroseSucrose, commonly called table sugar, is a moosaccharide of glucose and fructose with the molecular formula C12H22O11. This white, odorless, crystalline powder has a pleasing, sweet taste. It is best known for its role in human nutrition...
,
glucoseGlucose , a monosaccharide also known as - grape sugar, blood sugar, or corn sugar, is a very important carbohydrate in biology. The living cell uses it as a source of energy and metabolic intermediate...
,
mannitolMannitol is an organic compound with the formula . This polyol is used as an osmotic diuretic agent and a weak renal vasodilator...
,
sorbitolSorbitol, also known as glucitol, is a sugar alcohol that the human body metabolises slowly. It is obtained by reduction of glucose changing the aldehyde group to an additional hydroxyl group.-Sweetener:...
,
calcium carbonateCalcium carbonate is a chemical compound with the chemical formula CaCO
3. It is a common substance found in rock in all parts of the world, and is the main component of shells of marine organisms, snails, pearls, and eggshells. Calcium carbonate is the active ingredient in agricultural...
, and
magnesium stearateMagnesium stearate, also called octadecanoic acid, magnesium salt, is a white substance which is solid at room temperature. It has the chemical formula Mg2. It is a salt containing two equivalents of stearate and one magnesium cation...
.
Flavours
Flavours can be used to mask unpleasant tasting active ingredients and improve the likelihood that the patient will complete a course of medication. Flavourings may be natural (e.g. fruit extract) or artificial.
For example, to improve:
- -a bitter product - mint
MiNT is a free software alternative operating system kernel for the Atari ST and its successors. Together with the free system components fVDI , XaAES , and TeraDesk , MiNT provides a free TOS compatible replacement OS that is capable of multitasking.MiNT was originally released by Eric Smith as...
, cherryThe cherry is the fruit of many plants of the genus Prunus. It is a fleshy fruit that contains a single stony seed. The cherry fruits of commerce are usually obtained from a limited number of species, including especially cultivars of the wild cherry, Prunus avium.The name 'cherry', often as the...
or aniseis a flowering plant in the family Apiaceae native to the eastern Mediterranean region and southwest Asia known for its flavor that resembles liquorice, fennel, and tarragon.- Biology :Anise is an herbaceous annual plant growing to tall...
may be used
- -a salty product - peach
The peach is known as a species of Prunus native to China that bears an edible juicy fruit also called a peach. It is a deciduous tree growing to 4–10 m tall, belonging to the subfamily Prunoideae of the family Rosaceae...
, apricotThe Apricot is a species of Prunus, classified with the plum in the subgenus Prunus...
or liquoriceLiquorice or Licorice is the root of Glycyrrhiza glabra , from which a sweet flavour can be extracted. The liquorice plant is a legume , native to southern Europe and parts of Asia...
may be used
- -a sour product - raspberry
The raspberry is the edible fruit of a multitude of plant species in the subgenus Idaeobatus of the genus Rubus; the name also applies to these plants themselves...
or liquorice may be used
- -an excessively sweet product - vanilla
Vanilla is a flavoring derived from orchids of the genus Vanilla native to Mexico. Etymologically, vanilla derives from the Spanish word "", little pod. Originally cultivated by Pre-Columbian Mesoamerican peoples, Spanish conquistador Hernán Cortés is credited with introducing both the spice and...
may be used
Colours
Colours are added to improve the appearance of a formulation. Colour consistency is important as it allows easy identification of a medication.
Glidants
GlidantA glidant is a substance that is added to a powder to improve its flowability. A glidant will only work at a certain range of concentrations. Above a certain concentration, the glidant will in fact function to inhibit flowability A glidant is a substance that is added to a powder to improve its...
s are used to promote powder flow by reducing interparticle friction and cohesion. These are used in combination with lubricants as they have no ability to reduce die wall friction. Examples include colloidal
silicon dioxideThe chemical compound silicon dioxide, also known as silica , is an oxide of silicon with a chemical formula of ' and has been known for its hardness since antiquity. Silica is most commonly found in nature as sand or quartz, as well as in the cell walls of diatoms...
,
talcTalc is a mineral composed of hydrated magnesium silicate with the chemical formula H
2Mg
34 or Mg
3Si
4O
102. In loose form, it is the widely used substance known as talcum powder...
, and
magnesium carbonateMagnesium carbonate, MgCO3, is a white solid that occurs in nature as a mineral. Several hydrated and basic forms of magnesium carbonate also exist as minerals...
.
Lubricants
LubricantA lubricant is a substance introduced between two moving surfaces to reduce the friction between them, improving efficiency and reducing wear often used while having sex...
s prevent ingredients from clumping together and from sticking to the tablet punches or capsule filling machine. Lubricants also ensure that tablet formation and ejection can occur with low
frictionFriction is the force resisting the relative lateral motion of solid surfaces, fluid layers, or material elements in contact. It is usually subdivided into several varieties:...
between the solid and die wall.
Common minerals like
talcTalc is a mineral composed of hydrated magnesium silicate with the chemical formula H
2Mg
34 or Mg
3Si
4O
102. In loose form, it is the widely used substance known as talcum powder...
or silica, and
fatFats consist of a wide group of compounds that are generally soluble in organic solvents and largely insoluble in water. Chemically, fats are generally triesters of glycerol and fatty acids. Fats may be either solid or liquid at normal room temperature, depending on their structure and composition...
s, e.g. vegetable
stearinStearin , or tristearin, is a triglyceride, a glyceryl ester of stearic acid, derived from animal fats created as a byproduct of processing beef. It can also be found in tropical plants such as palm. It is used as tallow in the manufacture of candles and soap. In the manufacture of soap, stearin is...
,
magnesium stearateMagnesium stearate, also called octadecanoic acid, magnesium salt, is a white substance which is solid at room temperature. It has the chemical formula Mg2. It is a salt containing two equivalents of stearate and one magnesium cation...
or
stearic acidStearic acid or 18:0 is a saturated fatty acid. It is a waxy solid, and its chemical formula is C
18H
36O
2, or CH
316COOH. Its name comes from the Greek word stéar , which means tallow...
are the most frequently used lubricants in tablets or hard gelatin capsules.
Preservatives
Some typical preservatives used in pharmaceutical formulations are
- antioxidants like vitamin A
Vitamin A is linked to a family of similarly shaped molecules, the retinoids, which complete the remainder of the vitamin sequence. Its important part is the retinyl group, which can be found in several forms. In foods of animal origin, the major form of vitamin A is an ester, primarily retinyl...
, vitamin EVitamin E is a generic term for tocopherols and tocotrienols. Vitamin E is a family of α-, β-, γ-, and δ-tocopherols and corresponding four tocotrienols. Vitamin E is a fat-soluble antioxidant that stops the production of reactive oxygen species formed when fat undergoes oxidation...
, vitamin CVitamin C or L-ascorbic acid is an essential nutrient for humans, in which it functions as a vitamin. Ascorbate is required for a range of essential metabolic reactions in all animals and plants...
, retinyl palmitateRetinyl palmitate, or vitamin A palmitate is the ester of retinol and palmitic acid, with formula C
36H
60O
2.Palmitate is the major component of palm oil...
, and seleniumSelenium is a chemical element with the atomic number 34, represented by the chemical symbol Se, an atomic mass of 78.96. It is a nonmetal, chemically related to sulfur and tellurium, and rarely occurs in its elemental state in nature....
- the amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and one of the twenty R-groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H
2NCHRCOOH, where R is an organic substituent...
s cysteineCysteine is an α-amino acid with the chemical formula HO
2CCHCH
2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is nonpolar and thus cysteine is usually classified as...
and methionineMethionine is an α-amino acid with the chemical formula HO
2CCHCH
2CH
2SCH
3. This essential amino acid is classified as nonpolar.-Function:...
- citric acid
Citric acid is a weak organic acid, and it is a natural preservative and is also used to add an acidic, or sour, taste to foods and soft drinks. In biochemistry, it is important as an intermediate in the citric acid cycle and therefore occurs in the metabolism of virtually all living things...
and sodium citrateTrisodium citrate has the chemical formula of Na3C6H5O7. It is sometimes referred to simply as sodium citrate, though sodium citrate can refer to any of the three sodium salts of citric acid. It possesses a saline, mildly tart, flavor. For this reason,...
- synthetic preservatives like methyl paraben and propyl paraben
Propylparaben, the propyl ester of p-hydroxybenzoic acid, occurs as a natural substance found in many plants and some insects, although it is manufactured synthetically for use in cosmetics, pharmaceuticals and foods....
.
Sorbents
SorbentA sorbent is a material used to absorb liquids or gases. Examples include:*A material similar to molecular sieve material. It has a large internal surface area and good thermal conductivity. It is typically supplied in pellets of 1 mm to 2 mm diameter and roughly 5 mm length or as grains of the...
s are used for tablet/capsule moisture-proofing by limited fluid sorbing (taking up of a liquid or a gas either by
adsorptionAdsorption is the accumulation of atoms or molecules on the surface of a material. This process creates a film of the adsorbate on the adsorbent's surface. It is different from absorption, in which a substance diffuses into a liquid or solid to form a solution...
or by
absorptionAbsorption, in chemistry, is a physical or chemical phenomenon or a process in which atoms, molecules, or ions enter some bulk phase - gas, liquid or solid material. This is a different process from adsorption, since molecules undergoing absorption are taken up by the volume, not by the surface...
) in a dry state.
Sweeteners
Sweetener
A sweetener is a food additive which adds the basic taste of sweetness to a food; artificial sweeteners and natural sweeteners that aren't purely sugar are sugar substitutes.- Nutritive sweeteners :* Sugar alcohols* Honey* Fruits...
s are added to make the ingredients more palatable, especially in chewable tablets such as
antacidAn antacid is any substance, generally a base or basic salt, which counteracts stomach acidity. In other words, antacids are stomach acid neutralizers.-Action mechanism:...
or liquids like cough syrup. Therefore, tooth decay is sometimes associated with cough syrup abuse.
SugarSugar is a class of edible crystalline substances, mainly sucrose, lactose, and fructose. Human taste buds interpret its flavor as sweet. Sugar as a basic food carbohydrate primarily comes from sugar cane and from sugar beet, but also appears in fruit, honey, sorghum, sugar maple , and in many...
can be used to disguise unpleasant tastes or smells.
See also
- Pharmaceutics
Pharmaceutics is the discipline of pharmacy that deals with all facets of the process of turning a new chemical entity into a medication able to be safely and effectively used by patients in the community. Pharmaceutics is the science of dosage form design...
- Active ingredient
An active ingredient , is the substance in a drug or a pesticide that is pesticidal or pharmaceutically active. Terms in similar use include: active pharmaceutical ingredient and bulk active in medicine, or in pesticide formulations active substance may be used. Some medications and pesticide...
- Pharmacology
Pharmacology is the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and exogenous chemicals that alter normal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals...
- PlaceboA placebo is a sham medical intervention. In one common placebo procedure, a patient is given an inert sugar pill, told that it may improve his/her condition, but not told that it is in fact inert...
- Placebo effectPlacebo effect may refer to:* Placebo effect, the tendency of any medication or treatment, even an inert or ineffective one, to exhibit results simply because the recipient believes that it will work...
- Quality system
- Gluten-free diet
A gluten-free diet is a diet completely free of ingredients derived from gluten-containing cereals: wheat , barley, rye, and triticale, as well as the use of gluten as a food additive in the form of a flavoring, stabilizing or thickening agent...
External links