Excipients are any ingredients other than the active ingredient(s) included in formulations of medicines, medical devices, several cosmetic products or nutraceutical supplements. They are essential and integral components of products and are included to either aid the processing of the product during manufacture; to support and enhance stability, bioavailability, or patient usability, aid in product identification, or impart any other beneficial attributes that support overall safety and effectiveness of the product during use or storage.
In this article, we present a list of the20 most commonly used excipients (15 for solid dosage forms, and 10 for other dosage forms) based on search data (Pharmacentral.com and Google), and data from US FDA product registrations. The period covered is from January 2016 to December 2021).
Top 10 Excipients in Oral Solid Dosage Forms
The oral route remains the most convenient route of drug administration among patients and caregivers. Within this category, tablets are the most popular, and these can be in the form of standard compressed, orally disintegrating, chewable, effervescent or coated tablets. Many different excipients are included in tablet formulations, with the following materials being the most commonly used products (arranged in order of popularity):
#1. Microcrystalline cellulose
Microcrystalline cellulose is a purified, partially depolymerised cellulose. It is supplied as a white, odourless, tasteless, crystalline powder and is available in different grades, which are differentiated by particle size, density, and moisture levels.
Microcrystalline cellulose is currently the number 1 most used excipient in pharmaceutical products. Annual usage of microcrystalline tops US$ 1 billion in value, with the United States being the largest, single producer, followed by China.
Microcrystalline cellulose functions mainly as a binder-diluent in tablets and capsules, although it can also be used for other purposes, including:
- Capsule and tablet binder
- Tablet disintegrant
- Suspending agent
#2. Magnesium stearate
Magnesium stearate (octadecanoic acid magnesium salt) is a compound of magnesium and solid organic acids, mainly stearic and palmitic acids, in variable proportions. The organic acids are of vegetable or animal origin. It is supplied as a very fine, light, white impalpable powder of very low bulk density, and a faint stearic acid odour. It is greasy to the touch and adheres to the skin easily. Magnesium stearate is the second most widely used excipient in solid dosage forms. It is used as a tablet and capsule lubricant during manufacture. It is also used in cosmetics, foods, and pharmaceutical products as a hydrophobic ingredient to repel moisture (for example, in moisture barrier coatings).
#3. Pharmaceutical polymer coatings
The coating of solid dosage forms is now established in the pharmaceutical industry. In 2020, more than nine out of ten tablet-based drugs granted approval by the US FDA are coated, in some format. Read about excipients usage trends over the last 5 years through this link.
When used in the context of solid dosage forms, coatings are used either for aesthetics, to control moisture entry, or to modulate the rate of drug release. On the basis of these functions, coatings can be divided into three broad groups:
- Conventional pharmaceutical coatings
- Functional pharmaceutical coatings (non-release modifying)
- Functional pharmaceutical coatings (release-modifying)
Are you considering an alternative tablet film coating product? Click here to read a technical guide on evaluating an alternative film coating supplier or product.
#4. Croscarmellose sodium
Croscarmellose sodium is also referred to as crosslinked carboxymethylcellulose—sodium salt). It is a member of the trinity of well-known superdisintegrants, and the fourth most searched and used excipient, and arguably, the number one disintegrating agent in solid dosage forms. Its popularity stems from its consistent performance, compatibility with a wide range of active ingredients, and amenability with direct compression, wet granulation, roller compaction, and capsule filling.
#5. Colloidal Silicon Dioxide
Colloidal silicon dioxide is synthetic amorphous silica (chemical formula SiO2) and is distinct from other types of silica, including crystalline silica, silica gel or precipitated silica. Colloidal silicon dioxide is supplied as a white or almost white, light, fluffy, and extremely fine powder. Colloidal silicon dioxide is widely used in pharmaceuticals, cosmetics, and food products as an anticaking agent; emulsion stabilizer; glidant; suspending agent; thermal stabilizer; viscosity-increasing agent; desiccant, and solubility-enhancer. In tablets, colloidal silicon dioxide is also known to improve tablet strength, rate of disintegration, and stability (moisture binder).
#6. Lactose monohydrate
Pharmaceutical lactose monohydrate is a disaccharide made up of α-D-glucose, and D-galactose. It is a natural substance and the main carbohydrate in mammalian milk. To date, milk is the only known significant source of lactose. Lactose is a popular excipient due to its applicability as a tablet and capsule filler-diluent, lyophilisation aid in injectable products, and as an extender/filler in tablet coatings. Lactose monohydrate offers many benefits in solid dosage formulations, including being highly compactable and compatible with many active pharmaceutical ingredients. It isalso available in different particle sizes and crystalline forms, making it highly adaptable to the different needs of formulators.
#7. Povidone (Multiple grades)
Povidone is a synthetic linear polymer made up of 1-vinyl-2-pyrrolidinone monomers. Depending on the degree of polymerization different polymers of various molecular weights (or K values) are obtained. Povidones K25, K30 and K90 are the most commonly encountered in the pharmaceutical field and are supplied as fine, white, or cream-colored, odourless, and hygroscopic powders. Povidones are mainly used in solid dosage forms as wet granulation binders. They can also be used as suspending agents, viscosity-increasing agents, and a solubilisers.
Hypromellose or hydroxypropyl methylcellulose (HPMC) is a mixed cellulose ether obtained directly from naturally occurring plant cellulose fibres, followed by partial etherification with methyl groups and a small proportion of hydroxypropyl groups. It is supplied as an odourless and tasteless, white or creamy-white fibrous or granular powder and is available in multiple grades that vary according to molecular weight, degree of substitution, and viscosity.
Hypromellose is a multipurpose excipient that is used in wet granulation as a binder. It also serves as a suspending agent, viscosity-increasing agent, solubiliser, and matrix-forming polymer to sustain drug release. You can read more about its formulation (and how it differs from polyethylene oxide) by clicking through this link.
9. Sodium Starch Glycolate
Sodium starch glycolate is a modified potato starch excipient. Chemical modification is achieved through controlled cross-linking of the starch polymer backbone, which is followed by the introduction of carboxymethyl sodium groups (on C2 of the glucose molecule). It is as a white or almost white, free-flowing, very hygroscopic powder. Sodium starch glycolate is a superdisintegrant. It is widely recognised for its adaptability and compatibility with many active pharmaceutical ingredients and processing technologies.
Crospovidone is a water insoluble synthetic cross-linked polyvinyl pyrrolidone. It is manufactured by a polymerization process that results into a cross-linked povidone analogue in the form of ‘popcorn’ polymer or resin. It is supplied as a white or almost white, almost odourless hygroscopic powder. The different Crospovidone grades are used in pharmaceutical formulations on account of their swelling properties, porosity and insolubility as superdisintegrants, drug release and bioavailability enhancing agents, and as stabilising agents for suspensions.
Other Excipients that are Popular but not in the Top 10
#11. Sodium Bicarbonate
Sodium bicarbonate, otherwise known as sodium hydrogen carbonate, is a simple chemical substance having the formula NaHCO3. It is chemical name is Carbonic acid monosodium salt (molecular weight 84.01). It is supplied as an odourless, white, crystalline powder, with a salty alkaline taste. In solid dosage forms, sodium bicarbonate is used as a source of carbon dioxide in effervescent tablets and granules. It is also used to maintain an alkaline pH in formulations. In other dosage forms, sodium bicarbonate is used as a buffering agent and as a Na ion donor. It has also been used therapeutically in antacid formulations, in the management of metabolic acidosis and as a component in oral rehydration salts.
#12. Sodium Stearyl Fumarate
Sodium stearyl fumarate is a fumaric acid, octadecyl ester as the sodium salt. It is a fatty acid ester, with weak basic properties. It is supplied as a fine, white powder and used as a tablet and capsule lubricant. It is useful in formulations where traditional lubricants (magnesium stearate or stearic acid) cause problems, such as prolonged dissolution or strain-rate sensitivity.
#13. Dibasic Calcium Phosphate Dihydrate
Dibasic calcium phosphate dihydrate (DCP), also referred to as calcium hydrogen phosphate or calcium hydrogen orthophosphate, is the calcium phosphate having the formula, CaHPO4.2H2O. The “di” prefix is used to allude to the removal of two protons from phosphoric acid to form the anion, HPO42-. It is supplied as a white, odourless, tasteless and dense crystalline. DCP is mainly used as a tablet and capsule diluent. It may also be used as a source of calcium in dietary supplements.
#14. Maize starch (native and pregelatinized)
Maize starch is starch excipient obtained from corn (Zea mays). Pharmacopoeias distinguish between different types of starch, including potato, tapioca, wheat, rice or pea starch. Starch consists of two polymers: amylose, which is linear, and amylopectin, which is branched. Both polymers are based on α-D-glucose. The two polymers are arranged in a semicrystalline structure, although the exact chemical structure remains to be fully understood.
Starch is a multifunctional excipient. It is used as a tablet and capsule diluent, disintegrant and binder. It can be used in liquid formulations as a thickening agent, although hydrocolloid gums are superior in this respect. Despite the wide availability of newer and frankly, superior excipients (Hypromellose, povidone, mannitol, and superdisintegrants), starch still remains one of the most commonly used tablet binders, disintegrants and fillers today.
Mannitol (D-mannitol) is a hexahydric alcohol that is isomeric with sorbitol. It has a sweet taste, and imparts a cooling sensation on the tongue. Mannitol is supplied as a white, odourless, crystalline powder, or free-flowing granules. In recent years, mannitol has emerged a highly appealing excipient in the formulation and manufacture of tablets. It is used as a diluent in both capsules and tablets, although it imparts a level of sweetness, making it highly suitable for formulating buccal tablets. It is not hygroscopic, compressed extremely well and is generally inert, unlike lactose.
Top 10 Excipients in Parenteral, Topical, Oral Liquids and Inhalation Products
#1, Polysorbate 80
Polysorbate 80 is polyoxyethylene 20 sorbitan monoleate, commonly known by the brand name, TWEEN® 80. It belongs to a series of nonionic surfactants derived from ethoxylated sorbitan (a derivative of sorbitol) esterified with fatty esters. Polysorbate 80 has a molecular weight of 1310 (CAS number 9005-65-6). It is supplied as a yellow, oily liquid that is viscous at ambient conditions.
Polysorbate 80 is used as a dispersing agent, emulsifier, solubilising agent, suspending and wetting agent. It has been utilised in the preparation of oil-in-water emulsions, and to aid wettability of hydrophobic APIs in oral and parenteral suspensions. In biologics, Polysorbate 80 is one of the most used surfactants, where it is employed to prevent protein denaturation, aggregation, adsorption, and flocculation.
#2. Sodium chloride
Sodium Chloride is a metal halide composed of sodium and chloride. It contains no water of crystallisation, although at low temperature, hydrate formation is possible. Sodium chloride is supplied as a white crystalline powder or colourless crystals, with a strong saline taste.
The main use of sodium chloride in pharmaceutical products is as a tonicity agent in parenteral and nonparenteral liquid products. In solid dosage forms, sodium chloride has been used as a diluent, and a lubricant in capsules and direct compression tablets although its use in recent times has waned. Sodium chloride features in mRNA COVID-19 vaccine formulation due its role in controlling solid lipid nanoparticle size as well as controlling the ionic character of the formulation.
#3. Sodium Phosphate
Sodium phosphate is a general term for several chemical substances composed of sodium and phosphate. The British Pharmacopoeia describes three separate materials, corresponding to sodium dihydrogen phosphate anhydrous (CAS Number 7558-80-7), sodium dihydrogen phosphate monohydrate (CAS Number 10049-21-5), and Sodium dihydrogen phosphate dihydrate (CAS Number 13472-35-0). The USP-NF only lists the anhydrous and dihydrate, while the Ph.Eur only lists the dihydrate.
The anhydrous forms exist as white crystalline powders or granules, while the hydrated form are available as colourless or clear, crystals. They have no odour although they exhibit a slight saline taste. Irrrespective, sodium phosphate is used as a buffering agent and sequestering agent in injectable products. It can also be used therapeutically as a mild laxative, and in the treatment of hypophosphatemia.
#4. Polyethylene Glycol 400
Polyethylene glycol 400 belongs to a family of non-ionic homopolymers of ethylene oxide, having the formula, (CH2CH2O)n where n = 5-182 (molecular weight 200 – 8000). The USP-NF describes polyethylene glycol as an addition polymer of ethylene oxide and water.
Polyethlene glycol 400 is a liquid and occurs as a clear, colourless or slightly yellow viscous liquid having a bland taste but a slight, characteristic odour. It is miscible and dispersible in water and other polar solvents.
Polyethlene glycol 400 is used widely in pharmaceutical formulations, including parenteral, topical, ophthalmic, oral, and rectal products. It functions as a plasticizer, ointment base, solvent, emulsion stabiliser, and co-solvent.
Sucrose is a disaccharide composed of one molecule of fructose and one molecule of glucose. It is a natural substance obtained from sugar cane (Saccharum officinarum), sugar beet (Beta vulgaris), or other sources. It does not contain any other added substances. Sucrose can be supplied in many grades and formats, including as colourless crystals, crystalline masses, or as powders (coarse or fine). It has a characteristic sweet taste but no noticeable odour.
The main uses of sucrose is as a sweetening base in oral pharmaceutical products. It can also be used as a coating agent, granulation aid, suspending agent, tablet and capsule binder, filler-diluent, and as a viscosity (suspending) agent in oral solutions. Sucrose is also used as a diluent in freeze-dried protein products where it serves as a cryoprotectant and stabiliser.
Carbomers are a group of synthetic, high molecular weight, nonlinear polymers of polyacrylic acid that are crosslinked with a polyalkenyl polyether. They are all chemically related to each other, only differing in molecular weight, polymerization solvent or side groups. They occur as white, fluffy, hygroscopic powders having a characteristic odour of acrylic acid.
Carbomers are an important class of excipient. They are used as bioadhesive materials in the formulation of many topical products. They can also be used to control drug release, or as emulsifying agents, and rarely as tablet binders.
Citric acid is a simple organic substance that corresponds to 2-hydroxypropane-1,2,3-tricarboxylic acid. It was originally isolated from citrus fruits although commercial grades are now obtained synthetically. Citric acid occurs as a monohydrate or anhydrous. The USP-NF and Ph.Eur only lists the monohydrate, which is the official material. it occurs as a colourless or translucent crystals or as a white, crystalline powder, with a marked acid taste.
Citric acid is used as an excipient in oral and parenteral liquid pharmaceutical preparations as a buffering agent, antioxidant, flavour enhancer or preservative. Citric acid has been used to prepare effervescent granules and tablets.
Sodium citrate is generic term for the sodium salt of citric acid. Depending on the water of crystallisation, it may be referred to as sodium citrate hydrate, sodium citrate dihydrate, trisodium citrate. All forms of sodium citrate are designated by the code E331 in Europe. While the majority of pharmacopoeia describe sodium citrate as the dihydrate, the USP-NF states that sodium citrate may be either the dihydrate or anhydrous material.
The main function of sodium citrate in pharmaceutical products is as an alkalising agent, buffering agent and sequestering agent. It is used to adjust pH of solutions (oral and parenteral). The anhydrous material can be added to effervescent tablet formulations.
Dimethicone is a polydimethylsiloxane obtained by hydrolysis and polycondensation of dichlorodimethylsilane and chlorotrimethylsilane. It is available in different grades depending on the degree of polymerisation and molecular weight, yielding materials with kinetic viscosities nominally between 20 and 125,000 cSt (note that pharmaceutical grades are limited in viscosity to between 20 and 30 000 cSt). Dimethicones are clear, colourless liquids. They are used as antifoaming agents, emollients, lubricants and water repelling agents.
Phospholipids are a broad family of organic compounds having both polar (glycerol or other polyols) and non-polar (alkyl chains, or N-acylated sphingoid base) moieties. They have molecular weights ranging from 600 and 5000. They occur as white powders although they are also available as solutions (in methylene chloride or chloroform). They are obtained from natural sources, including eggs or soybeans although they can also be synthesised industrially. Lecithicin is a partially purified mixture of naturally-sourced phospholipids.
Being amphiphilic, phospholipids self-associate to form several important structures, including liposomes and lipid nanoparticles. They are therefore used as surfactants, dispersing agents, emulsifiers, solubilising and wetting agents.
The last 30 years have witnessed a significant change in the role played by excipients in drug formulation, their production, and availability, and how they are tested and regulated. Of great importance has been the growth of biological drug products. The result of these market changes is the decreasing proportion of products marketed as solid dosage forms (tablets, capsules, granules, etc) from 70-80% two decades ago, to just over 50% today due to the increasing contribution of parenteral drug products (biologics) over the last decade.