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Pharmaceutical Tablet Film Coatings

A pharmaceutical film coating is a polymer-based membrane applied onto solid dosage forms, such as tablets, capsules and granules, in order to impart certain desired attributes that are otherwise absent in the uncoated product.

In this post, we’ll tell you what film coatings are, why they are used in pharmaceutical products and how they are applied onto solid dosage forms.

What is a pharmaceutical film coating?

The term ‘coating’ usually implies a membrane formed directly on a substrate. It separates two phases between which fluids (gases, vapours or liquids) may be exchanged.

It is distinguished from ‘film’, a term used interchangeably with coating, which, however, refers to a preformed, stand-alone membrane (a film becomes a coating when applied onto a substrate) (Mwesigwa, 2006).

When used in relation to solid dosage forms, a film coating can be defined a polymer-based thin membrane applied onto the surface of tablets, capsules, granules and spheroidal unit dosage forms.

The coating generally imparts certain desirable attributes to the dosage that are otherwise absent in the uncoated form.

Such attributes include impartation of colour and branding marks, alteration of drug release properties, protection of sensitive ingredients or masking offensive odours or tastes, among others.

Pharmaceutical coatings are usually dense, non-porous films obtained from polymeric substances and are typically ≤ 100 μm thick (Hogan, 1995) although films with much higher thickness are not atypical.

Note that the use of polymer film coatings is not limited to solid dosage forms: many other products are routinely encased in polymer films of various types. For example, medical devices are coated with silicone resins to provide lubricity and protection.

Types of polymer film coatings

The practice of coating solid dosage forms (tablets, capsules, granules and spheroids) is a very old practice that has been undertaken for several centuries.

There are references to the use of mucilages to coat pills in Greco-Arab and Islamic herbal medical scripts.

As sugar became more widely available in the 19th century, the food and confectionery industry developed pan coating as a means for improving aesthetics of candy.

This technology was subsequently borrowed and adapted for use in the pharmaceutical industry, and remained the only means for coating until the early 1950 when the American pharmaceutical company, Abbott Laboratories marketed the first polymer film coated tablet.

This set a precedent for further introduction of many other polymers for use in pharmaceutical coatings. Presently, although sugar coated drug products are still widely marketed the vast majority of products utilise polymer film coatings.

Polymer coatings can be broadly categorized into three groups based on their functional roles:

(1) Conventional coatings

Conventional coatings are sometimes known as non-functional or immediate release coatings.

They are the most commonly encountered type of tablet coating.

The reason they are known as non-functional coatings is because they are designed to dissolve rapidly in the gastrointestinal tract without any significant impact on the rate of drug release in the gut.

Conventional coatings serve several purposes, including:

  • protective
  • aesthetics
  • masking taste or odours
  • improving mechanical strength of the core
  • facilitating product handling
  • reduction of the risk of interaction between incompatible components, and
  • reduction of dust and the associated explosion hazards

The main requirement for conventional coatings is pH independent solubility, as mentioned above, so as to have a minimum influence on drug release of the core.

(2) Delayed release coatings

Delayed release coatings are mainly of the enteric type.

They are designed to prevent disintegration of the dosage form in the stomach. However, on reaching the intestine, delayed release coatings disintegrate to release the drug for absorption or local action.

There are many reasons why an enteric coating may be applied to solid dosage forms:

  • Firstly, they may be utilised to protect certain drug substances which are hydrolysed in the stomach by gastric secretions (e.g., acids and enzymes),
  • They can be used to prevent gastric distress associated with acidic drugs (e.g., aspirin or other NSAIDs),
  • They can help deliver drugs intended for local action in the intestines, e.g., intestinal antiseptics, to deliver drugs that are optimally absorbed in the intestines to their prime absorption site, or to effect a delayed response to the dosage form.

Therefore, the ideal enteric-coating should be impermeable to gastric juices but easily susceptible to intestinal juices.

The majority of enteric polymers are have carboxyl ionizable groups that become protonated in acid media but form salts in alkaline pH enabling them to dissolve in the intestinal juices.

(3) Sustained release coatings

The third category is for covers coatings used to control the rate of release of drug substances from a dosage form and extend the release time over several hours.

Sustained release coatings are also known as controlled, extended or prolonged release coatings, although teach of these terms has specific meanings.

Generally, the most common mechanism of sustaining release is controlling the diffusion rate of the drug through the polymer membrane.

Depending on the diffucion mechanism sought, different release kinetics can be obtianed, such as zero-order (constant release), first-order release kinetics, or pulsatile or sigmoid release patterns.

Note that in the literature, the term ‘modified release’ coating is also sometimes used. This term is non-specific and covers both delayed release and sustained release coatings.

Controlled release coatings serve a variety of purposes:

  • They are used to achieve more effective therapy while eliminating the potential for both under- and overdosing.
  • Controlled release coatings are also used to achieve the slow release of highly soluble and or permeable drugs, fast release of low-solubility drugs, or delivery of drugs to specific sites, such as the colon.
  • Lastly, it is not uncommon that pharmaceutical companies to use controlled release technologies as a way of achieving brand line extension or to add marketing depth to an existing brand.

Materials used in polymer film coatings

A film coating is constituted from a variety of materials that include a polymer, a plasticizer, and other additives (surfactant, colorants/pigments and lubricants).

Once combined and dissolved or dispersed in a solvent or aqueous medium, the different ingredients are sprayed onto the substrate and allowed to form a thin, continuous envelope.


The polymer is the film former and the main component on the formulation.

The ideal polymer is one capable of producing smooth, thin films that are reproducible under routine coating conditions.

The range of materials that can be used as film formers is very wide and covers materials that may be natural, synthetic or semi-synthetic.

Polymers used in conventional film coatings

This category includes:

  • cellulose ether derivatives, e.g., hypromellose (also called hydroxypropyl methylcellulose), methylcellulose, hydroxypropylcellulose and sodium carboxy methylcellulose
  • vinyl polymers, e.g., polyvinyl alcohol and polyvinylpyrrolidone
  • polymethacrylates, mainly copolymers of butylmethacrylate, (2-dimethylaminoethyl) methacrylate and methylmethacrylate
  • Other polymers e.g., zein, modified starches and polysaccharides

Polymers used in delayed release film coatings

  • This category mainly includes enteric polymers such as:
  • polymethacrylate derivatives (e.g., ethylmethacrylate copolymer)
  • polyvinyl acetate derivatives, e.g., poly(viny acetate phthalate), and
  • cellulose derivatives, e.g., cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropyl methylcellulose acetate phthalate, and hydroxypropyl methylcellulose acetate succinate.

Polymers used in extended/sustained-release film coatings

This category includes the following compounds:

  • cellulosic derivatives, e.g., ethylcellulose and cellulose acetate
  • polyacrylates, such as Eudragit R series of polymers; and
  • polylactides, poly(lactide-co-glycolides and polyorthoesters


Plasticizers are low molecular weight organic esters added to coatings to facilitate processing.

They modify generic properties of the polymer rendering them easy to process and or to perform as membranes.

Although many compounds, covering diverse functions like phthalates, aliphatics, epoxides (vegetable oils), etc., and even polymers, possess plasticizing properties, only few are approved for pharmaceutical use.

These include polyols such as glycerol, propylene glycol and polyethylene glycols, organic esters such as phthalates, dibutyl sebacate, and triacetin, vegetable oils/glycerides such as castor oil.

Miscellaneous additives

Additives serve a variety of purposes: Colorants are used for individualization of the product by colour.

They may be pigments, e.g., amaranth, γ-carotene, or dyes such as lakes of aluminium or opacifiers, which are used to impart opacity. Talc and titanium dioxide are mainly used opacifiers.

Fillers and anti-tack agents are used to provide coating solids to the formulation and to reduce tackiness.

They include talc, microcrystalline cellulose, glyceryl monostearate, stearic acid and magnesium stearate.


Solvents permit uniform film formation and application over the entire substrate.

Those which have been used for film coating include water, ethanol, ethanol/water, and various other solvent/solvent mixtures.

Their selection is based on the following criteria:

(i) empirically; according to the “like dissolves like” rule;

(ii) qualitatively, based on the assessment of intermolecular forces; and

(iii) quantitatively, based on solubility parameters

Up to the early 1970s, organic solvents were the main stay of film-coating applications. However, due to increasing costs, concerns about toxicity and effects on the environment, a move to aqueous based systems was prompted.

Therefore, water is the preferred coating medium today although a few companies still use organic solvents.

How Film Coatings Are Applied

Film coating of solid dosage forms in the pharmaceutical industry is undertaken in a specialised coating equipment, such as solid coating pans, perforated pans or fluidised coater.

The process involves loading the cores into the pan, which is spun at a low to moderate speed, while a stream of hot air is pumped into the bed of rotating cores.

A solution or dispersion of the coating (polymer, plasticizer, pigment, etc) is then pumped and sprayed into the moving bed at a pace matched with the rate of evaporation of the solvent, leading to the formation of a thin film on the core surface.

This is illustrated in the infographic below:

The different steps involved in a typical tablet film coating, as it is carried out presently, can be split into several stages:

  • Preparation of the coating dispersion

This step is required in order to effectively transform coating components into a medium that can be efficiently applied onto the coating substrates.

Typically, the coating materials are dissolved or dispersed in a water, water-alcohol solutions, acetone or ethyl acetate. Organic solvents are rarely used due to the potential hazards from flammability and toxicity.

  • Droplet generation/atomization and transfer onto substrates

Atomization is the process of breaking up the coating liquid into a spray of droplets. In film coating, atomization allows the polymer coating to be efficiently and uniformly transferred onto the substrate.

The main mechanism of atomization involves pumping the coating fluid through a pneumatic nozzle. As the liquid emerges at the nozzle tip the air stream that surrounds it disrupts its flow to create a fine mist.

  • Droplet drying, coalescence and adhesion

Upon contact with the substrates, heat and mass transfer take place between the droplets, heated air and the substrate. Water evaporates from the droplets and is transferred into the air by convection. The solid payload deposits onto the surface, adheres and dries on the surface to create a film.

The choice between water and solvent-based coatings

Even though organic solvents are much easier to process, there has been a steady move away from their use in pharmaceutical coatings due to various reasons.

  • The different reasons include:
  • rising costs of solvents
  • hazards and risks due to flammability
  • regulations
  • environmental concerns

These factors, together with the availability of better designed equipment and introduction of high performance, fully-formulated coating systems, mean that aqueous coatings are by far the most widely used systems today.

Examples of Film Coating Formulae

The following are gexamples of film coating formulae based on the concepts outlined above:

Convetional coatings

High gloss coating formula

Material% w/wFunction
Sodium carboxymethylcellulose40Film former
Sodium citrate2Stabiliser
Pigments & oxides10Pigments
Colours & dyes5Colorants

General purpose coating (PVA-based)

Material% w/wFunction
Polyvinyl alcohol40Film former
Polyethylene glycol 335020.2Plasicizer

General purpose (HPMC-based)

Material% w/wFunction
HPMC 60640Film former
Lactose monohydrate12Extender
Polyethylene glycol 335018Plasticizer

Enteric coating

Material% w/wFunction
Methacrylic acid Copolymer Dispersion (30% aqueous dispersion)16.6Enteric polymer film former
Polyethylene Glycol 6000 (10% squeous solution1.6Plasticizer
Antifoam emulsion0.2Foam suppressant

Summary about Pharmaceutical Film Coatings

The oral route of drug administration is the most popular means by which people take medication.

It allows the development of immediate and modified-release products with unparalleled ease.

One of the commonest means of modifying drug release in oral dosage forms is the use of polymeric film coatings. Polymers are selected for this purpose because they are able to form thin membranes or coatings that are not only strong but can also impart many useful properties to the dosage form.

It is also on the basis of the functional basis of polymer coatings that they are classified, thus, we have conventional or non-functional coatings, extended release (enteric coatings) and controlled release coatings.


Pharmacentral has a strict referencing policy and only uses peer-reviewed studies and reputable academic sources. We avoid use of personal anecdotes and opinions to ensure the content we present is accurate and reliable.

Definition and Importance of Excipients in Medicinal Products

Excipients are essential but integral components of medicines. They perform several functions that are important for the safe use of medical products. However, there still remains a lot of ambiguity on what excipients are, their safety and if they should be removed from products, especially products intended for very young children. This article aims to answer all these and many other questions you have always had but did not who to ask or where to find answers.


What is a Pharmaceutical Excipient?

An excipient is defined as any ingredient other than the active ingredient(s) included in formulations of therapeutic goods, such as medicines, vaccines and medical devices. Excipients are also used in some cosmetic products, and nutraceutical food supplements.

In most products, excipients constitute the largest component of the formulation, being anywhere from 40 to 99+ percent by weight. This is why excipients are often referred to as ‘bulking’ agents.

If we take the example of PANADOL tablets – a commonly used pain killer medicine, each PANADOL tablet contains 500mg of paracetamol, which is the active ingredient. However, there are other ingredients in the product, as outlined below:

All the listed ingredients with the exception of paracetamol are the excipients in this product. They are typically listed in in the SmPC document (Summary Product Characteristics), which you can find by searching in a public compendia, such as the Electronic Medical Compendium.


Functions of Excipients in Medicinal Products

Excipients aid processing, disintegration and dissolution in the body and help protect the drug substance against unfavourable conditions, both in vivo and in vitro.

They also provide bulk, so that the product can be easily picked by the patient and conveniently used. This can be a big challenge for elderly patients or very young children. Click here to read our article highlighting the importance of empathy in new drug development. We also recently discussed the importance of dysphagia and odynophagia (swallowing problems) and how they create health inequalities if not addressed by pharmaceutical companies, which you can read through this link.

Suffice to say all the different functions undertaken by excipients work together to permit companies such as Glaxo, Astra Zeneca or Pfizer (and many others which you can see listed here) to manufacture safe, efficacious drug products that meet the quality standards set by health authorities, such as the US Federal Drug Agency (FDA), European Medicines Agency (EMA), or the Medicines and Healthcare products Regulatory Agency, and countless others around the world.

The interrelationship between excipient functionality and the pharmacological activity of the active ingredient is illustrated in this infographic below:

<img src="excipientsapiinterrelationship.jpg" alt=excipients api interrelationship">

Origins of the word ‘excipient’

There are several (often conflicting) opinions on the origin of the word, excipient. What seems certain is its etymological basis, which is the Latin word excipiēns, the present participle of excipere. Excipere essentially means ‘to take out’ and translates into, in the modern sense, ‘everything else other than’. Thus, we can envisage excipients as materials other than active principles, used to aid the processing, elaboration or manufacture of the medicinal, cosmetic or nutraceutical products.

Such ingredients include materials used to protect, support or enhance the product’s quality, safety, stability, availability, acceptability and identity, or enhance any other attribute that allow products to be used safely and effectively.

Are Excipients Inactive?

An important question today, at least within the excipients space, is whether excipients are inactive, that is, passive bystanders that do nothing other than to hung about in products. Some have gone as far as to say that these materials are unnecessarily added into products for marketing purposes and should be avoided by consumers. This is understandable.

We can say for certain that for the most past, excipients are inert (or correctly, intended to be biologically inert). But this is not without exceptions. Generally, natural or partly-natural excipients, many of which are part of the normal human diet, are biologically inert, that is, they do not elicit a pharmacological effect. The definition of natural and nature-inspired excipients is provided in this article, which you can read by clicking through this link.

Examples of such excipients include, but are not limited to the below:

Many other fully synthetic substances, such as povidone, acrylic copolymers and inorganic minerals (such as calcium carbonate and calcium phosphate) are also established as inert.

Within the pharmaceutical sector, the principal requirement for any excipient is functionality, which simply refers to fitness for a named purpose. But fitness for one use does not mean fitness for use in another, and depending on factors such as route of administration, age, patient group or dosage, a material that is fine for oral use may be hazardous when injected or inhaled.

We also know for certain that, while adverse reactions to excipients are generally rare, they still do occur, and excipients can be hazardous especially when they are not used correctly. This is why consumers are advised to always read labels and liaise with health care professionals to avoid the use of products that might contain ingredients likely to cause adverse events. Click here to read about safety assessments of excipients.

Many excipients have caused problems in paediatric and adult patients, thus the idea that excipients are inactive materials is somewhat misleading, and possibly dangerous .

Examples of well-documented, non-biologically active or ‘problem’ excipients are listed in the table below:

Excipient name/classReported issues/problemsSources
SulfitesWheezing, dyspnoea and anaphylactoid reactionFlorence A T (2010), An Introduction to Clinical Pharmaceutics, Pharm Press
Benzalkonium chlorideBronchoconstrictionFlorence A T (2010), An Introduction to Clinical Pharmaceutics, Pharm Press
AspartameHeadaches and hypersensitivity Several
SaccharinDermatological reactions; should be avoided in children with sulfar allergiesSeveral
Benzyl alcoholIn high concentrations, potentially lethal in neonatesSeveral
Various dyesCross-sensitivity, headaches, urticaria, exacerbation of asthma symptomsSeveral
LactoseProblematic in lactase deficient individualsSeveral
Propylene glycolLocalised contact dermatitits when used topically, lactic acidosis after absorptionFlorence A T (2010), An Introduction to Clinical Pharmaceutics, Pharm Press
TalcAcute respiratory distress syndromeUS FDA
Tocopherol Polyethylene Glycol (TPGS)Inhibition of P-gp mediated transportBoman et al., J Pharm Sci (2003), 92: 1250-1261
PolysorbateInhibition of P-gp mediated transportBoman et al., J Pharm Sci (2003), 92: 1250-1261
polyethoxylated castor oilInhibition of P-gp mediated transportBoman et al., J Pharm Sci (2003), 92: 1250-1261
Polyethylene glycolInhibition of P-gp mediated transportBoman et al., J Pharm Sci (2003), 92: 1250-1261

Types of Excipients

The are many different classes of excipients as are product categories. The Handbook of Pharmaceutical Excipients, an influential reference on excipients, currently lists over 400 materials. They differ by chemical properties, function and source (mineral, natural or synthetic). They may be in the form of liquids, semi-solids, solids as well as gases.

A list of different materials classified by chemical group, function and source is shown below:

Chemical GroupExamples
Hydrocolloid gumsPectin, Xanthan gum, Acacia, Agar
Mineral claysBentonite, Kaolin
Cellulose polymersHypromellose, Ethylcellulose, Microcrystalline cellulose
StarchesMaize starch, Tapioca starch, Potato starch
Amino acids & ProteinsAlbumin, Glycine
Sugars & PolysaccharidesDextrose, Polydextrose, Fructose, Lactose
Vinyl polymersPolyvinyl alcohol
MineralsCalcium carbonate, Magnesium carbonate, Sodium chloride
PetrochemicalsLiquid paraffin
SiliconesDimethicone, Cyclomethicone, Simethicone
PolyolsSorbitol, Mannitol, Maltitol, Xylitol
Acrylic polymersCarbomers
Organic & Inorganic compoundsCitric acid, Ethylparaben
Triglycerides, Oleochemicals & DerivativesGlyceryl monostearate, Oleic aicd, Magnesium stearate
GlycolsPolyethylene glycol, Polyethylene oxide
Alkoxides & SilicatesSilica, Calcium silicate
Emulsifiers & SurfactantsSodium lauryl sulfate, Tween 80, Hydrogenated castor oil
Fillers & DiluentsLactose, Microcrystalline cellulose, Maize starch, Calcium phosphate
Film coatingsHypromellose, Ethylcellulose, Polyvinyl alcohol
BindersMaize starch, Povidone, Sodium carmellose
Sweeteners & FlavoursSucralose, Xylitol, Acesulfame K, Strawberry flavour
PlasticizersSorbitol, Triethylcitrate, Glycerine
Drug release modifiersPolyethylene oxide, Hypromellose, Ethylcellulose
Solvents & SolubilisersEthanol, Cyclomethicone
Viscosity modifiers & Suspending agentsXanthan gum, Sodium carmellose
Antioxidants & Stabilising agentsVitamin C, Vitamin E
Vaccine adjuvantsAluminium hydroxide
Gelling agentsCarbomers, Pectin, Carrageenan
Glidants, Lubricants & Anti-sticking agentsSilica, Magnesium stearate, Talc
PreservativesEthylparaben, Potassium sorbate, Benzalkonium chloride
Disintegrating agentsStarch, Sodium starch glycolate
Buffers & pH modifiersSodium hydrogen carbonate, Phosphoric acid
Excipient SourceExamples
Chemical synthesisSodium lauryl sulfate, Tween 80, Carbomer
MineralsTalcum, Kaolin, Calcium carbonate, Sodium chloride
Plant derivedMaize starch, Glucose, Mannitol
Animal derivedLactose, Gelatin
Products of fermentationXanthan gum

Excipients Used in Oral Solid Products

The oral route, and specifically, oral solids (mainly tablets, capsules and powders) is the most widely used route for administration of pharmaceutical products. Some studies indicate that the oral route accounts for over 80% of all medicines administered. Here is a list of the top 20 excipients most commonly used in oral solid dose formulations, including granulation binders, diluents for tablets and capsules, disintegrants, lubricants, antiadherents, glidants, colouring agents and flavours.

Common NameMain Function
AlginatesBinder and disintegrating agent
Calcium carbonateFiller, diluent, pigment & source of calcium. Opacifier & colorant
Calcium phosphate (all grades)Filler, diluent, pigment & source of calcium
GelatinCoating agent & binder
Croscarmellose sodiumDisintegrating agent
CrospovidoneDisintegrating agent
Povidone (PVP)Tablet binder
Silicon dioxideGlidant
Sodium starch glycolateDisintegrating agent
Dextrose (glucose)Filler, diluent & binder
Functional & Aesthetic coatingsAesthetics & modified drug release
Lactose (Spray-dried, monohydrate & anhydrous)Filler & diluent
Magnesium stearateLubricant
MannitolFiller & diluent
Native & modified starchesFiller, binder & disintegrating agent
SorbitolFiller & diluent
Microcrystalline celluloseFiller & dry binder
Sodium bicarbonateFiller & alkalising agent
HypromelloseBinder & modified-release agent
Sodium chlorideDiluent & tonicity agent

Excipients Used in Oral Liquid Products

Suspensions and oral liquids are an important dosage form particularly in children and the elderly or when drug products have poor solubility or cannot be formulated into tablets or capsules.

The top 12 excipients used in pharmaceutical suspensions, including syrup or dry suspensions are shown below.

Xanthan gumSuspending agent and viscosity modifier
Polyethylene glycol (mainly PEG 400)Solvent and Co-solvent
CarboxymethylcelluloseSuspending agent and viscosity-increasing agent
Flavours (mainly citrus, strawberry & vanilla)Taste masking and flavour enhancement of bitter products
MaltitolSuspending agent & diluent
SucroseSuspending agent, viscosity modifier and sweetener
EthanolSolvent & Co-solvent
SorbitolSweetener, Suspending agent & diluent
SucraloseTaste masking and flavour enhancement of bitter products
Propylene glycolSolvent & Co-solvent, flavour enhancer
PolysorbateSurfactant and dispersing aid
Parabens (All)Preservatives
Acesulfame PotassiumSweetener
Sodium/Potassium BenzoatePreservative

Excipients Used in Topical Products

Administration of medicines through the skin is referred to as ‘transdermal drug delivery’. It has grown in importance in recent decades owing to several advantages, including:

  • improved patient adherence
  • convenience
  • options for sustained and controlled release
  • avoidance of gastric irritation, and
  • avoidance of first-pass effect

Even though excipients used in topical products are not intended to be swallowed, they must be safe and comply with pharmacopoeia standards and meet expected quality standards.

A list of the top 15 commonly used topical excipients include:

Carbomers (all)Viscosity increasing agents, Suspending agents, Emollients & Moisturizer
Petrolatum & Mineral OilsEmollient & Skin conditioner, Carrier
GlycerinMoisturiser and Co-solvent
Glyceryl MonostearateEmulsifier and Co-emulsifier
Cetostearyl AlcoholEmollient, Skin emulsifieir & Viscosity-increasing agent
Polyethylene GlycolGelling agent, Solvent & Co-solvent
Parabens (Methy, Propyl & Butyl)Preservatives
Tocopherol (Vitamin E)Antioxidant & Skin conditioner
Dimethicone & CyclomethiconeEmollient, Skin conditioner & Carrier
Waxes (Bees, Microcrystalline & Others)Refatting & Stiffening agent
Vegetable OilsEmollient & Carrier
Isopropyl MyristateEmollient, Skin penetrant & Carrier
Glyceryl MonooleateBioadhesive material, Emollient & Emulsifier
Hard FatsSuppository base
PolysorbatesSurfactants, Dispersants & Co-emulsifiers

Excipients Used in Injectable Products

The parenteral route covers all products administered by injection directly into the body’s issues.

This class of medicines can be divided into three groups:

  • injection into the skin (subcutaneous, intramuscular, & intracutaneous),
  • intraveneous infusions, and,
  • peridural and subarachnoid routes

Injectable products offer numerous advantages over other routes of administration, including precise and adjustable dosing, predictable bioavailability, and fast onset of action.

In acute-patient-care settings, injectable drugs are the main forms of drug administration.

Since injections introduce substances directly into the body bypassing many of the body’s defences, there are extra safeguards expected from excipients.

One of these is that they should be sterile, and if the volume of the product is large (>100ml), they should be free of pyrogens and endotoxins (fragments of bacterial cell walls).

A list of the 15 most commonly used excipients in injectable products and the roles in the formulation is below:

Excipient nameFunction
Arachis oilCarrier & Oleaginous vehicle
Benzyl alcoholPreservative
Dextrose (Glucose)Bulking agent & Cryoprotectant
EDTAChelating agent
Ethyl oleateCarrier and Solvent
Human serum albuminStabiliser
Hydrogenated castor oilSurfactant & Solubilising agent
Lecithin (and other phospholipids)Surfactant & Solubilising agent
Macrogol 15 HydroxystearateSurfactant & Solubilising agent
PolysorbateSurfactant & Solubilising agent
PolysorbatesSurfactant, Solubilising agent & Dispersant
Potassium or Sodium PhosphateBuffering agent
Sodium chlorideTonicity adjusting agent
Sodium hydroxidePH adjusting agent
Sodium citrateBuffering agent
Sodium metabisulfitePreservative & Antioxidant
Polyethylene glycolSolvent
Zinc chlorideTonicity adjusting agent
Hydrochloric acidPH adjuster

Excipient Safety Assessment

The issue of excipient safety is a major point of contention in public discourse, and possibly one of the major sources of misinformation on medical products.

Before any material can be used in a product as an excipient, regulatory agencies require manufacturers to undertake rigorous testing and guarantee that it is safe for use.

This has not always been the case – in fact, in the early days of the pharmaceutical industry, excipients were considered pharmacologically inert and rarely regulated.

This lack of control lead to many issues, including significant harm to the public. You can listen to our podcast on this through this link.

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Over the years, as products have become more complex and the ingredients used in them even more elaborate, safety testing of excipients is now mandatory.

Suffice to say, regulatory agencies, such the US FDA, MHRA and EMA, have approved lists for excipients, either in form of pharmacopoeia monographs or databases (e.g IIG Database, Dictionnaire Vidal or Japanese Pharmaceutical Excipients compendium) as well as standards for manufacture (e.g Good Manufacturing Practices) and distribution/handling (Good Distribution Practices) that manufacturers must comply with.

Read about excipient safety assessment here.

The bottom-line is that the pharmaceutical industry works through multiple checks and balances to ensure that quality and safety requirements are adhered to before any material can be used in a drug product.


Frequently Asked Questions About Excipients

What criteria are used to select excipients?

The main criteria for selection of an ingredient is functionality. Examples of the different functions were outlined above, but generally include:

  • maintainance of a product’s integrity (containment, stability, freedom from contamination, etc)
  • making up the volume
  • aiding in the release characteristics of the active ingredient
  • facilitating identification, etc.

But in addition to functional suitability, the excipient must be compatible with other excipients and the active. Incompatibilities can compromise product quality and safety of users.

Thus, the most suitable excipients for the job are selected, taking care that those that are selected have a genuine function in the product.

Indeed, product manufacturers are now required to state and justify the role of excipients in the product. It is no longer acceptable to add a material that does not have a clearly established and validated function.

For example, a preservative should not be included in sterile, single-dose products, such as injections or eye drops. As a general rule, only excipients that perform a needed function are required to be included int he formulation.

Which materials can be excipients?

In the USA, only materials officially recognised in the United States Pharmacopoeia-National Formulary (USP-NF) and/or listed in the US FDA Inactive Ingredients Database (IIG Database) can be used in pharmaceutical products as excipients.

The USP-NF defines the quality requirements for excipients in form of a monograph while the IIG Database shows which material is already in use and the types of products its used in.

The Europe Union does not have a bloc-wide list of approved excipients although individual countries have compendia that list approved materials for their jurisdictions.

There is however, a European Pharmacopoeia, which has excipient monographs similar to the USP-NF.

An important question is whether materials without a monograph or those not listed in official compendia be used as excipients?

Generally, a material not officially listed in a pharmacopoeia or recognised in compendia may still be used in pharmaceutical products. In deed there are various such products, including for example, butylene glycol and several others.

However, regulatory agencies require detailed assessment and evidence of that material’s safety, toxicity and quality profile. This can be time-consuming and expensive process, and for this reason, few manufacturers dare go down this route, preferring to use established/proven materials as excipients.

Which excipients should not be used in infants?

In 2008 the EU passed Regulation 1901/2006 on medicinal products for paediatric use, following which the European Medicines Agency published recommendations for pharmaceutical formulas intended for children (0-18 years old).

A few standout excipients in this regulation include:

ExcipientFunctionRegulatory Recommendation
Benzyl alcoholPreservativeNot to be given to neonates
EthanolSolvent and preservativeBest avoided in children under years old. The WHO proposes the following:Not more than 0.5% for children under 6 years old Not more than 5.0% for children between 6 and 12 years oldNot more than 10.0% for children over 12 years old
Propylene glycolSolventAvoid in children under 4 years old
Colouring agentsColouring & maskingShould be avoided in all paediatric products unless absolutely necessary. AZO dyes are banned


Which companies manufacture excipients?

Excipient manufacturers are a diverse group of companies, from public to private, small to large. You can see our compilation of the most innovative excipient manufacturers or the size of the excipients market by following through these links. Here, we provide a selection of the most important excipient companies currently:

CompanyCountry HQProduct Focus
BASFGermanyIbuprofen, Omega-3, Polxamer 188, Hydrogenated Castor oil, Povidone & Lactose
DupontUnited StatesSilicones & Elastomers
IFFUnited StatesMicrocrystalline cellulose, Flavours and Fragrances
ColorconUnited StatesFilm coatings
Evonik AGGermanySilica, Polymers, Carbomers and Antimicrobials
CARGILLUnited StatesCarbohydrate and polysaccharides
Lubrizol CorporationUnited StatesCarbomers
ShinEtsuJapanSilicones, Cellulose polymers
CrodaUnited KingdomOleochemicals
Roquette FreiresFranceCarbohydrate and polysaccharides
Tereos Sugars & SweetenersFranceCarbohydrate and polysaccharides
JH NanhangChinaVinyl polymers (Povidones)
SolvayFranceSodium bicarbonate
AsahiJapanPolysaccharides & microcrystalline cellulose
Abitec CorporationUnited StatesOleochemicals
Angus Chemical CompanyUnited StatesBuffers and salts
Dow ChemicalUnited StatesPolymers & cellulosics
Meggle GroupGermanyPolysaccharides & microcrystalline cellulose
DFE PharmaThe NetherlandsPolysaccharides & microcrystalline cellulose
Tate & LyleUnited KingdomPolysaccharides & microcrystalline cellulose
CP KelcoUnited StatesHydrocolloids
AshlandUnited StatesFilm coatings, Povidones
JRS PharmaGermanyPolysaccharides & microcrystalline cellulose
SasolSouth AfricaOleofins
Eastman Chemical CompanyUnited StatesPolymers
Merck KGAAGermanyDiversified chemicals, Pigments & buffers
IOI OleochemicalsGermanyOleochemicals
FirmenichSwitzerlandFlavours and fragrances
Kerry GroupIrelandLactose, coatings & flavours
SPI PharmaUnited StatesODT systems, mannitol
CabotUnited StatesSilica
BudenheimGermanyCalcium salts
ImerysFranceTalc, calcium salts & kaolin
HallstarUnited StatesOleochemicals
InolexUnited StatesOleochemicals
Dr. Paul LohmannGermanyCalcium salts
Lonza AGSwitzerlandPreservatives & capsules
Nippon GohseiJapanPolyvinyl alcohol
CelaneseUnited StatesSweeteners
British SugarUnited KingdomSugar
WackerGermanySilicones and silica
WH GraceUnited StatesSilica
SeppicFranceFilm coatings
Novo NordiskDenmarkPreservatives
Mingtai Chemicals CoChina (Taiwan)Microcrystalline cellulose


Although does not manufacture excipients, we have distribution arrangements and partnerships with many reputable firms. If you have any questions on any materials or would like to sample or purchase get in touch through here.

Should I avoid non-medical products that use excipients?

Since many excipients are chemically-derived industrial ingredients they may not sit well with some consumers of dietary nutraceutical products who prefer natural, eco-friendly and ‘clean’ labelled.

What’s useful to remember is that pharmaceutical excipient manufacturers mainly focus on achieving and maintaining functional performance and safety, which requires materials to undergo extra levels of processing and purification.

Ultimately, the choice to avoid dietary products with excipient-grade ingredients is down to personal choice and what people believe best suits their values and motives.

Where can I obtain more information on excipients?

There are many authoritative sites and places to get information on excipients:

You can of course, use our own PharmaCentral Products pages – where we have monographs of the most important and commonly used excipients listed. You will find all the information you need regarding any material. And the good thing is that it is 100% free.


Cited Literature and Sources Used

To ensure our content is accurate and scientifically sound, Pharmacentral implements a strict referencing policy. We only use peer-reviewed studies and reputable academic sources and authors.

Elder DP, Kuentz M, Holm R. Pharmaceutical excipients – quality, regulatory and biopharmaceutical considerations. Eur J Pharm Sci. 2016 May 25;87:88-99. doi: 10.1016/j.ejps.2015.12.018. Epub 2015 Dec 14. PMID: 26699228.

Fabiano V, Mameli C, Zuccotti GV. Paediatric pharmacology: remember the excipients. Pharmacol Res. 2011 May;63(5):362-5. Doi: 10.1016/j.phrs.2011.01.006. Epub 2011 Jan 15. PMID: 21241804.

Alison Haywood, Beverley D Glass. Pharmaceutical excipients – where do we begin? Australian Prescriber (Accessed October 2021).

Excipients – an overview (Science Direct)

Overview of pharmaceutical excipients used in tablets and capsules. (Accessed October 2021).


Safety of Pharmaceutical Excipients: Definition and Assessment Methods

Since the thalidomide disaster, ensuring that medicines are safe before they are approved for sale to the public has become one of the most important tasks of regulatory agencies.

However, while most people are familiar with clinical trials and how they are used to assess safety and efficacy of new medicines (technically, the active ingredients), excipient safety is rarely featured, and has remained a mystery.

In this short article, we will explain how the safety of different pharmaceutical excipients, such as parabens and vaccine adjuvants, is assessed by pharmaceutical scientists today.

What is excipient safety?

Whether a particular excipient is safe or not depends on what safety actually means. The commonly agreed definition of safety is the absence of undesirable pharmacodynamics effects (adverse and side effects) that a particular substance exerts on the physiological function of the living organism upon exposure within its therapeutic range.

Excipient toxicity, another closely related term to safety, and often used interchangeably, actually refers to the degree a material is poisonous, i.e its ability to cause injury.

Undesirable effects include sensitization, allergic reactions, anaemia, jaundice, kidney damage, nerve damage, interference with vision, blood cell count, et cetera.

It is important to also note that safety and toxicity depend on many other factors, not just the dose, duration or route of exposure of that material, per se. This is sometimes referred to as the intrinsic safety/toxicity.

Some excipients subtly alter physiological properties, such as increased gastrointestinal motility, permeability of membranes, metabolism and excretion. This type of toxicity is known as extrinsic.

Examples of undesirable effects in commonly used excipients are shown in the table below.

Excipient nameFunction in the productAdverse effects
Propylene glycolSolventCNS effects, especially in children under 4 years old
Benzyl alcoholPreservativeHypersensitivity reactions, respiratory system effects
Ethanol (alcohol)Solvent and co-solventIntoxication
PolysorbatesSolubilising agent & surfactantE-Ferol syndrome
Hydrogenated castor oil derivativesVehicle and solubilising agentAnaphylaxis
ParabensPreservativeReports of oestrogenic effects, especially for propylparaben. Also hypersensitivity reactions & anaemia in neonate
SaccharinArtificial sweetenerHypersensitivity and photosentivity reactions
Glucose and sucroseSweetenerDental caries
Benzalkonium chloridePreservative & surface active agentBronchospasm when used in combination with asthma drugs. Ear damage
Sodium metabisulfiteAntioxidantWheezing and chest tightness in asthmatic children
AspartameArtificial sweetenerContra-indicated in patients with phenylketonuria
Colours (e.g Azo dyes)ColorantsSensitivity reactions. Some reports of hyperactvity in children
Chlorhexidine (all salts)Biocide & preservativeHypersensitivity reactions, irritation of conjuctiva and corneal damage in high concentrations
MentholFlavourInhalation in large quantities causes ataxia and CNS depression. Hypersensitivity reactions are reported
LactoseFiller and diluentIn lactose intolerant individuals, cramps, diarrhoea and flatulence

Safety of an excipient is formally assessed by monitoring its effects on vital systems, in particular, the cardiovascular, the central nervous and respiratory systems.

A material’s toxicity will depend on a variety of factors, including the dose of the substance, duration and route of exposure.

For a long time, excipients were considered inert substances, included in products to facilitate production and/or improve convenience during use.

This definition, in the strictest sense, now only applies to natural, simple substances, such as honey, simple sugars and other substances that are well characterised and known to be inert.

The importance of safety

Modern pharmaceutical products are anything but simple mixtures; they are complex engineered products in which several ingredients are combined to produce specific characteristics.

Many of these complex materials have the potential to adversely affect consumers, particularly if used in large quantities.

For this reason, there is a process for ensuring that the safety of every ingredient in the formulation is well studied and mapped out.

Safety is especially important since excipients are often present in very high proportions relative to the active ingredient.

But safety is also dependent on the way a product is handled, for instance during formulation or manufacturing, it may be exposed to high heat or humidity, leading to an increase in the probability to generating secondary products and impurities to be introduced into the product.

During use, the patient may not store is correctly, leading to further degradation to produce toxic impurities.

Excipients may also interact with the medicinal agent, other excipients in the formulation, the container or the atmosphere, leading to many more undesirable effects.

Thus, safety and toxicity of the pure substance as well as any degradants must be known, both by regulatory agencies and product manufacturers, and rightly so, by the public who are the ultimate users of medical products.

Methods used to assess excipient safety

Mapping out the intrinsic and extrinsic safety, as well as understanding potential risks and post-approval monitoring are what constitute the universe of excipient safety assessment.

Some of the tests and investigations conducted on excipients to understand their instrinsic and extrinsic toxicological profiles are shown in the infographic below.

Note that many of these resemble those tests done on new chemical entities:<img src="pharmaceuticalexcipientssafety.png" alt="excipeints safety studies">The challenge for this approach, however, is that there can be no end to it – rather like the proverbial length of a piece of string.

This problem (of unending safety assessment) can be overcome by adopting a risk-based view of safety; by seeking to understand and address any potential risks during the life history of the material, from the earliest stages of synthesis, through to product development, launch and use.

Risk-based assessment of safety

A risk-based approach to safety and toxicity requires manufacturers of the excipient and medical products to adhere to good manufacturing practices (GMPs) when handling excipients, very much similar to those for active ingredients and follow guidelines set by regulatory agencies.

Some of the requirements from regulatory agencies include routine testing of excipients to ascertain and verify a material’s identity, purity, traceability of batches, and quality, which are all important determinants for safety and efficacy of the product.

The particular safety assessment pathway taken is largely dictated by precedence of use. The exact requirements depend on the regulatory agencies, which operate under different rules.

For practical reasons, we’ll focus on three regulatory agencies: the US Food and Drug Administration (FDA), the European Medicines Agency, and the Japanese Ministry of Health, Labour, and Welfare:

Excipients with precedence of use

If an excipient has already been used in an approved pharmaceutical product, is a food additive, or any product with human exposure, that is, where previously safety tests were carried out, it is considered to have precedent.

Such materials are already registered for use and may be included in official pharmacopoeia or compendia.

The US Food and Drug Administration (FDA) has an excipient database (FDA Inactive Ingredients Database) which lists all excipients and their precedence of use.

There is also the United States Pharmacopoeia and National Formulary that carries monographs of approved excipients for use there. You can click here to access the Inactive Ingredients Database.

Related post:

  • Full list of excipients Generally Recognised As Safe

The European Medicines Agency does not have a list of ingredients; however, individual member countries have compendia that list approved materials and their routes of administration.

In France, for instance, this is the “Dictionnaire Vidal,” and in Germany the “Die Rote Liste”. The European Pharmacopoeia, just like the USP-NF carries monographs of excipients approved across the bloc.

In Japan, the Japanese Ministry of Health, Labour, and Welfare has a precedence of use compendium known as the Japanese Pharmaceutical Excipients dictionary, and the Japanese Pharmacopoeia. Both show the different excipients that have been previously used in drug formulations in that country, with the description of their characteristics, and the maximum dose used in the different administration routes.

Excipients with no precedence of use

Excipients that have never been used in any products and therefore have no safety assessments undertaken formally are considered novel excipients.

Novel excipients are materials being used in a drug product for the first time or a new route of administration.

In other words, they are not included in the Inactive Ingredient Database, United States Pharmacopeia-National Formulary (USP-NF), European Pharmacopoeia, Japanese Pharmacopoeia, or other compendia, including the “Handbook of Pharmaceutical Excipients.

Also, approved excipients that have undergone chemical modification, however minor, are considered novel excipient by regulatory agencies.

For these materials, there are several guidelines in operation by respective regulatory authorities before they can be permitted for use in medicines.

For instance, the US FDA requires nonclinical and clinical assessments to be undertaken. These studies not only aims to assess the excipient’s intrinsic safety but also the extrinsic Safety profile.

For further reference, please see USP-NF 26 General Chapter <1074 > “Excipient Biological Safety Evaluation Guidelines”, and IPEC’s New Excipient Evaluation Guidelines.

The excipient manufacturer is expected to develop full safety information recommended in the guidelines, based on the material’s future use and dosage form.

The battery of tests to be conducted are described in these guidelines.

Excipient Safety Assessment: Two common Questions

Pharmacopoeia: Are excipients required to be listed in the pharmacopoeia?

A common question that often arises is whether an excipient is required to have a monograph before it can be commercialised. The simple answer is no. There is no regulatory requirement for a monograph.

However, it is always preferable to present an excipient with a monograph or a complementary document that is relevant, because it means that such a material has established quality specifications for pharmaceutical use.

If the excipient is present in several pharmacopoeias, the manufacturer is expected to ensure conformity for all monograph requirements, present in all pharmacopoeias, before its commercialization to the global market.

The manufacturer demonstrates that methods used to test the material are valid and provide assurance that the excipient, when tested by these methods, conforms to all requirements.

When the excipient is not present in any pharmacopoeia or other monograph in a compendium, the manufacturer can establish an own specification, based on a similar monograph present in the pharmacopoeia.

Pharmacopoeia: Can excipients with no monographs be used in medicines?

An excipient that is not written in any pharmacopoeia can be used in a drug product, even if there is no monograph. However, regulatory authorities normally require a detailed evaluation of the excipient’s safety and toxicity, which can be an expensive endeavour.

If there is no monograph available, a specification can be based on the manufacturer’s own experience and in the chemical and physical properties of the excipient according to the intended use of administration.

Inclusion of a novel material into the pharmacopoeia depends on its commercial importance and its use in a pre-approved drug product.

In this case, both the excipient manufacturer and medicinal product manufacturer can request regulatory agencies or the national pharmacopoeia commission to draw up a new monograph, provided the novel excipient has received approval through its use in a marketed drug product.

At this stage, the novel excipient is considered approved for use by the stated route of administration and in the stipulated dosage levels as in the approved drug.

What about Drug Master Files?

The first step to introduce a new excipient in the market is the determination of its functionality, route of administration, identification, and stability of the intended API for a drug formulation.

Once these steps are all set, a document with all information known as a Drug Master File (DMF), or European Certificates of Suitability (CEP) is created.

This document provides all the technical information such as specifications and test methods for raw materials, in-process testing, the finished excipient product, manufacturing process, safety, packaging details, and content label.

In the United States, the supplier submits the DMF to FDA, which is held in confidence by the administration. In Europe, the DMF only exists for APIs and is not available for excipients.

CEPs are used for pharmaceutical excipients, which may be treated in two ways: CEPs for excipients listed in Ph. Eur and CEPs for excipients not listed in the Ph. Eur.

Other supplementary tests for assessing safety

Excipient assessments for generic drug products

During generic product development, the sponsoring company may choose to use excipients that are different from the innovator formulation either because of a change in route of administration or dosage forms.

In this case, the formulations and or route of administration are different but the API is already established and known.

In both cases, excipients will be selected based on the function they perform, compatibility with the API and other formulation components and any other considerations, such as cost, material availability and the company’s own experience and preferences.

Regulatory approval will only be granted if it’s established that the excipients are suitable to be used in the new formulation, via the intended route of administration or the dosage form specified for the new drug product.

Investigations of Excipient – API Incompatibilities

Since some excipients react with and can modify excipients or the API, additional compatibility studies between excipients and APIs are mandated. Such reaction products may be harmful or alter the stability of the API.

There are many ways excipient compatibility studies can be done, the most common ones being differential scanning calorimetry (DSC) or isothermal calorimetry, using simple blends of the excipient and API in simple ratio.

Thus, assessing the nature of these interactions therefore aims to select only materials that are compatible with the drug and will not compromise the stability or safety of the formulation. If incompatibilities are established, the formulation team will aim to alleviate the incompatibilities.

Presence of impurities and residual solvents

The presence of impurities and solvents in the product formulations need to be identified and controlled within specified limits. Impurities and solvents can be introduced during the material’s manufacture, product formulation or production.

Residual solvents are classified into three main groups, depending on their toxicity and potential harm:

Class 1 solvents are to be avoided in the formulation because they are known or suspected carcinogens and hazardous to the environment. Examples of Class 1 solvents include carbon tetrachloride and benzene.

Class 2 solvents are to be limited because while being non-genotoxic are suspected to have neurotoxicity or teratogenicity, or suspected to be causative agents of the same. Examples of Class 2 solvents include acetonitrile, methanol and dioxane.

Class 3 solvents have low toxic potential to humans however, they may be limited in terms of the total quantities allowed in the formulation. Examples of Class 3 solvents include ethanol, acetone and ethyl acetate.

Excipient stability studies

Excipient stability studies are carried out with the aim of determining whether the material maintains its quality over the time period it is used. The excipient will be studied under various environmental conditions, such as high temperature, light and humidity.

A major objective of excipient stability studies is to determine the expiry date or re-test period, which refers to the time period within which the raw material is expected to remain within specification, and therefore, safe for use in the drug product. A material that has expired and or has not been re-tested is not safe for use, and should be destroyed.

Market surveillance

The final, and by no means the least aspect of safety assessment is market surveillance post-launch of the product onto the market, whereby healthcare professionals and the public report any side and adverse effects encountered into a central database. The data are then collated and analysed for patterns and trends that might point to previously unreported toxicity to ensure the product is withdrawn before it can harm more people.

The significance of market surveillance is evident when you consider the fact that twenty percent of adverse effects and toxicities are discovered during this phase of market surveillance.

Conclusions on excipient safety

For a long time only the quality, efficacy, and safety of the API was considered as the most important aspects of a new medicine.

This approach has now changed, and manufacturers are required not only to study an excipient’s safety but they must also justify its inclusion in a product.

Any ingredient used in the product must be beneficial and help optimize the performance of the product, both during the manufacture and also during use.

The process of assessing safety involves a battery of established tests that determine the physiological effects of the material, including potential effect on the cardiovascular, respiratory and central nervous system.

In addition, any interactions with other components in the product must be studied and understood fully.

The rule of the thumb is to simplify formulations as much as possible and reduce the number of excipients to those that are absolutely necessary.


Sources used

American Academy for Paediatrics: Committee on Drugs. ‘Inactive’ ingredients in pharmaceutical products update (Subject review). Pediatrics 1997;99(2):268–278. Available at: (accessed August 2021)

Turner MA, Duncan JC, Shah U et al. Risk assessment of neonatal excipient exposure: lessons from food safety and other areas. Adv Drug Deliv Rev 2014;73: 89–101. DOI:10.1016/j.addr.2013.11.003

C.L. Winek, History of excipient safety and toxicity, Drugs and the pharmaceutical sciences, 103 (2000) 59-72. PMID: 27262205. DOI: 10.1016/j.xphs.2016.03.019




FDA GRAS Listed Excipients (Incl Searchable Database)

Substances that are established components of human or animal food can, upon qualification by a scientific committee, be granted GRAS status.

For pharmaceutical excipients, GRAS status represents an interesting class of materials for product formulators since their safety profile is already considered and sufficiently known.

In this post, we will review the ins and outs of GRAS listed excipients and summarise their implications when it comes to inclusion in products, especially if they are intended for use in the United States of America.

What is the GRAS Excipients List?

“GRAS” is an abbreviation used by the US FDA for food ingredient or additives that the agency has deemed safe. It stands for Generally Recognized As Safe.

The basis for GRAS is sections 201(s) and 409 of the Federal Food, Drug, and Cosmetic Act, under which these substances are reviewed and approved by the FDA.

Typically, any substance that has undergone the required safety assessment by a team of experts and deemed not to cause harm when used as intended can be added to the GRAS ingredients list.

This allows the manufacturers of such materials to assign GRAS status to the material.

Alternatively, a material that was in use in the human diet before 1958, and used in such significant quantities across the population of the United States without any safety concerns. may be assigned GRAS status.

Excipients are a diverse group of ingredients other than the active ingredient(s) added to medicines, medical devices, some cosmetic products or nutraceutical food supplements.

They perform specific functions, such as promoting the product’s stability, bulk or ease of use.

Any food ingredient on the FDA’s GRAS List that is also approved for use as an excipient is a GRAS Listed excipient, provided it is manufactured and used in accordance with the provisions of sections 201(s) and 409 of the Federal Food, Drug, and Cosmetic Act.

Note that all excipients need to meet minimum safety requirements before they can be used in products for use by the public.

There are several certification schemes around the world, including the listing in an official pharmacopoeia, such as the United States Pharmacopoeia as well as country compendia or lists, such as the Japanese Pharmaceutical Excipients list.


Purpose of the GRAS List

The main purpose of the GRAS list is to speed up the approval and market introduction of new products and to reassure the public that the products they are consuming are safe and wholesome.

Even though the FDA has premarket approval responsibilities over food additives, a company can add an ingredient into human food products without first seeking the agency’s approval provided the ingredient has GRAS status for the intended use.

Picture a situation where regulatory agencies such as the US FDA needed to assess every ingredient de novo each time new products were launched onto the market?

Not only would this be demanding in terms of human resources for regulatory agencies but it would put strain onto new product manufacturers who would need to resubmit data on these ingredients.

Highly repetitive and unnecessary, and would slow down innovation.

Instead, having a pre-approved list of excipients permits manufacturers and scientists to create new products and meet new demands by easily incorporating these materials into their products without having to apply for fresh approvals.


History of GRAS Status

In 1958, the US Congress passed the Food Additves Amendment to the FD&C Act as a response to widescale public outcry on the rising use chemicals in food products.

The basic tenet of this law was to mandate that before any substance could be added to food products or used in food processes, companies had to demonstrate to the FDA that the substance was safe.

The FDA was required to define the conditions under which substances were to be used. Congress also stipulated mechanisms and pathways for demonstrating safetyestablished. You can read more about this topic through this link.

Suffice to say, Congress adopted a two-step definition of food additives. The first step covers substances that become components of food while the second is for substances generally recognised by experts to be safe.


GRAS Listing Process

Any material that is not a food additive and is not required to be approved through the food additive process can be added to the GRAS List provided the necessary assessments have been undertaken.

The process of GRAS listing is schematically illustrated below:



Currently GRAS Listed Excipients

There are currently just over 370 substances with GRAS status, a number of which are also approved excipients with monographs in the USP-NF, Ph.Eur or JP.

Typically, GRAS Listed excipients include natural, synthetic or semi-synthetic materials. A list of these GRAS-listed excipients, links to their descriptions and uses is shown below:

Excipient Common NamePharmacopoeia MonographUses and Routes of Administration
AcaciaUSP-NF, Ph.Eur, BP, JPOral and topical products as an emulsifying agent; stabilizing agent; suspending agent; tablet binder and viscosity-increasing agent
Adipic acidUSP-NF, Ph.EurI.M injections as an acidifying agent and buffering agent. In oral products as a flavouring agent
AgarUSP-NF, Ph.Eur, BP, JPOral and topical products as an emulsifying agent; stabilizing agent; suppository base; suspending agent; sustained-release agent; tablet binder; thickening agent and viscosity-increasing agent
Alcohol (Ethanol)USP-NF, Ph.Eur, BP, JPOral and topical products as an antimicrobial preservative and solvent. In topical products as disinfectant, skin penetrant and solvent. Approved for use in parenteral products as a solvent
Alginic AcidUSP-NF, Ph.EurOral and topical products as a drug release-modifying agent; stabilizing agent; suspending agent; sustained release agent; tablet binder; tablet disintegrant; tastemasking agent; viscosity-increasing agent
Alpha TocopherolUSP-NF, Ph.Eur, BP, JPAntioxidant
Ammonium AlginateFCC & FDA IIG DatabaseDiluent; emulsifying agent; film-forming agent; humectant; stabilizing agent; thickening agent
Ammonium ChlorideUSP-NF, Ph.EurOral products as an acidifying agent
Anise (Star Anise)Ph.EurOral products as a flavouring substance
Ascorbic AcidUSP-NF, Ph.Eur, BP, JPOral (liquids) as an antioxidant
Ascorbyl PalmitateUSP-NF, Ph.Eur, BPOral and topical products as an antioxidant
BentoniteUSP-NF, Ph.Eur, BP, JPOral products as an adsorbent/retardant for cationic drugs. In topical products as a stabilizing agent; suspending agent and viscosity increasing agent
Benzoic AcidUSP-NF, Ph.Eur, BP, JPParenteral products (IM & IV), oral liquids and topical products as an antimicrobial preservative
Butylated HydroxyanisoleUSP-NF, Ph.Eur, BP, JPParenteral products (IM & IV), topical and oral (oil-based liquids) products as an antioxidant
Butylated HydroxytolueneUSP-NF, Ph.Eur, BP, JPParenteral products (IM & IV), topical and oral (oil-based liquids) products as an antioxidant
Butylene GlycolFDA IIG DatabaseTopical products as an antimicrobial preservative; humectant; solvent; water-miscible cosolvent. In parenteral products as a solvent/co-solvent
Calcium AcetateUSP-NF, Ph.Eur, BPOral and topical products as an antimicrobial preservative.
Calcium AlginateFCC & BPC (1973)Oral products (liquids) as an emulsifying agent; stabilizing agent and thickening agent. As a tablet disintegrant
Calcium CarbonateUSP-NF, Ph.Eur, BP, JPOral products (solid dosage forms) as a buffering agent; filler and coloront in coatings; opacifier; tablet and capsule diluent
Calcium ChlorideUSP-NF, Ph.Eur, BP, JPOral (suspensions), ophthalmic and parenterals (dry powders) as an antimicrobial preservative and desiccant.
Calcium Hydrogen Phosphate AnhydrousUSP-NF, Ph.Eur, BP, JPOral (tablets and capsules) as a diluent/filler
Calcium Hydrogen Phosphate DihydrateUSP-NF, Ph.Eur, BP, JPOral (tablet and capsule) diluent/filler
Calcium HydroxideUSP-NF, Ph.Eur, BP, JPTopical and oral (suspensions) products as an alkalizing agent or pH adjuster/buffer (creams, lotions)
Calcium LactateUSP-NF, Ph.Eur, BP, JPOral products as an antimicrobial preservative; buffering agent; crosslinking agent. In tablets and capsules as a diluent/filler
Calcium SilicateUSP-NFOral products as an adsorbent; anticaking agent; opacifier and diluent/filler (tablets)
Calcium StearateUSP-NF, Ph.Eur, BP, JPOral products as a tablet and capsule lubricant
Calcium SulfateUSP-NF, Ph.Eur, BPOral products as a tablet and capsule diluent
Calcium TriphosphateUSP-NF, Ph.EurOral (tablets and capsules) as an anticaking agent; buffering agent; glidant and diluent/filler
Canola OilUSP-NF, Ph.EurTopical products as an emollient; lubricant; oleaginous vehicle
Carnauba WaxUSP-NF, Ph.Eur, BP, JPOral products as a coating agent
Carob Bean gumFCCTopical and oral products as a stabilizer, thickener and gelling agent
CarrageenanUSP-NFOral and topical products as an emulsifying agent; gel base; stabilizing agent; suspending agent; sustained-release agent; viscosity-increasing agent
Castor OilUSP-NF, Ph.Eur, BP, JPTopical products as an emollient; oleaginous vehicle and solvent. In oral, parenteral and parenteral (IM) products as an oleaginous vehicle
CelluloseUSP-NF, Ph.Eur, BP, JPOral products (tablets and capsules) as a glidant, diluent and tablet disintegrant. In topical products as an adsorbent; suspending and thickening agent.
Cellulose AcetateUSP-NF, Ph.Eur, BPOral products (tablets & capsules) as a coating agent; extended-release agent and diluent
Citric AcidUSP-NF, Ph.Eur, BP, JPAcidifying agent; antioxidant; buffering agent; chelating agent; flavor enhancer; preservative
Citric Acid MonohydrateUSP-NF, Ph.Eur, BP, JPOral products (tablets, gummies, liquids & coatings) as an acidifying agent; antioxidant; buffering agent; chelating agent; flavour enhancer and preservative. In parenteral and ophthalmic products as an acidifying, chelating and buffering agent
Corn StarchUSP-NF, Ph.Eur, BP, JPOral products (tablets & capsules) as a diluent; disintegrant and binder. In topical and liquid products as a thickening agent
DextratesUSP-NFOral products (tablet and capsules) as a binder and diluent
DextrinUSP-NF, Ph.Eur, BP, JPOral products as a stiffening and suspending agent (liquids) and binder and diluent (tablets and capsules)
DextroseUSP-NF, Ph.Eur, BP, JPOral products (solids and liquids) as a tablet and capsule diluent and binder; as a sweetening and tonicity agent in liquid products
Disodium Edetate (EDTA)USP-NF, Ph.Eur, BP, JPOral, topical, ophthalmic and parenteral products as a chelating agent
ErythritolUSP-NF, Ph.Eur, BP, JPOral solid and liquid products as sweetening and taste-masking agent. In tablet and capsule formulations as a diluent and as a platicizer in coatings
Erythorbic AcidUSP-NFOral and topical products as an antioxidant
Ethyl LactateFCCOral and topical products as a solvent/co-solvent for insoluble resins in emulsions. As a flavouring agent in oral liquids
Ethyl MaltolFCCOral (liquids) products as a flavour and flavour enhancer
Ethyl VanillinUSP-NFFlavour and flavouring agent
EthylcelluloseUSP-NF, Ph.Eur, BP, JPOral products as a coating agent; tablet binder; tablet filler; and controlled-release excipient. In topical products as a viscosity increasing agent
FructoseUSP-NF, Ph.Eur, BP, JPOral products. In solid dose forms as a dissolution enhancer and diluent. In liquid dosage forms as a flavoring and sweetening agent
Fumaric AcidUSP-NFOral solid & liquid products as an acidulant and flavouring agent. In liquid products as an antioxidant
GelatinUSP-NF, Ph.Eur, BP, JPOral products. In tablets as a binder, coating agent and film-forming agent. In oral liquids as a gelling agent; suspending agent and viscosity-increasing agent
Glucose LiquidUSP-NF, Ph.Eur, BP, JPOral products (liquids) as a sweetening agent. In oral solids as a binding liquid and coating agent
GlycerinUSP-NF, Ph.Eur, BP, JPOral products as an antimicrobial preservative; plasticizer; cosolvent and sweetening agent. In topical products as an emollient; humectant; solvent/co-solvent
Glycery PalmitostearateFDA IIG DatabaseOral products as a coating agent; gelling agent; release-modifying agent; sustained-release agent; tablet and capsule diluent. Occasionally as a tablet and capsule lubricant and taste-masking agent
Glyceryl BehenateUSP-NF, Ph.Eur, BPOral products as a coating agent; tablet binder and tablet and capsule lubricant. In topical products as a thickening and viscosity-increasing agent
Glyceryl MonooleateUSP-NF, Ph.Eur, BPTopical products as an emollient; emulsifying agent; emulsion stabilizer and a nonionic surfactant. In oral products as a sustained-release agent
Glyceryl MonostearateUSP-NF, Ph.Eur, BP, JPTopical products as an emollient; emulsifying agent; solubilizing agent and stabilizing agent. In oral products as a sustained-release agent; tablet and capsule lubricant and anti-adherent in film coatings
Glyceryl Triacetate (Triacetin)USP-NF, Ph.Eur, BPOral products as a humectant; plasticizer and solvent
GlycineUSP-NF, Ph.Eur, BP, JPParenteral products as a buffering agent; bulking agent; dietary supplement; freeze-drying and agent. For oral products as a tablet disintegrant and wetting agent
Guar GumUSP-NF, Ph.Eur, BPOral liquid products as a suspending and viscosity increasing agent. In oral solids as a tablet binder; disintegrant
Hydrogenated Soy Bean Oil
Hydroxyethylmethyl CelluloseUSP-NF, Ph.EurOral and topical products as a coating agent; suspending agent; tablet binder; thickening agent and viscosity-increasing agent
Hydroxypropyl CelluloseUSP-NF, Ph.Eur, BP, JPOral products as a coating agent; emulsifying agent; thickener & stabilizing agent; suspending agent and tablet binder. Topical products as a thickening and viscosity-increasing agent.
Hydroxypropyl StarchJPEOral products as a binding agent; disintegrant; emulsifying agent; thickening agent and viscosity-increasing agent
HypromelloseUSP-NF, Ph.Eur, BP, JPOral, topical and ophthalmic products as a bioadhesive material; coating agent; controlled-release agent; dispersing agent; dissolution enhancer; emulsifying agent; emulsion stabilizer; extended-release agent; film-forming agent; foaming agent; granulation aid; modified-release agent; mucoadhesive; release-modifying agent; solubilizing agent; stabilizing agent; suspending agent; sustained-release agent; tablet binder; thickening agent; viscosity-increasing agent.
Hydroxyethylmethyl CellulosePh.EurOral and topical products as a coating agent; suspending agent; tablet binder; thickening agent; viscosity-increasing agent
InulinUSP-NF, Ph.EurOral products as sweetening agent and tablet binder
IsomaltUSP-NF, Ph.EurOral products as a coating agent; granulation aid; medicated confectionary base; sweetening agent; tablet and capsule diluent
Lactic AcidUSP-NF, Ph.Eur, BP, JPTopical and oral products as an acidifying agent. Topically as a skin conditioner
LactitolUSP-NF, Ph.EurOral products as a sweetening agent and as a tablet and capsule diluent
LactoseUSP-NF, Ph.Eur, BP, JPOral, parenteral and inhalation products. In dry powder inhaler as a carrier; as a lyophilization aid in injectable products and as a tablet binder and capsule/tablet diluent/filler
Lauric AcidFCCOral and topical products as a lubricant and as an emulsifying agent and surfactant
LecithinUSP-NF, Ph.Eur, BP, JPOral, topical and parenteral products an emulsifying and solubilizing agent. As emollient in topical formulations
Linoleic AcidFCCTopical products as an emulsifying agent and skin penetrant
Locust BeanPh.Eur, BPOral products as a thickener; viscosity modifier; free-water binder and a suspending agent/stabilizer
Magnesium CarbonateUSP-NF, Ph.Eur, BP, JPOral products as an adsorbent; and as a tablet and capsule diluent
Magnesium OxideUSP-NF, Ph.Eur, BP, JPOral products as a tablet and capsule diluent, anticaking agent and glidant
Magnesium SilicateUSP-NF, JPOral pharmaceutical formulations and food products as a glidant and an anticaking agent
Magnesium StearateUSP-NF, Ph.Eur, BP, JPOral products as a tablet and capsule lubricant
Magnesium TrisilicateUSP-NF, Ph.Eur, BPOral products as a glidant.
Malic AcidUSP-NF, Ph.Eur, BPOral products as an acidulant; antioxidant; buffering agent; chelating agent and flavouring agent
MaltitolUSP-NF, Ph.Eur, BPOral (solid dosage) products as a coating agent; diluent; granulation aid and sweetening agent
MaltodextrinUSP-NF, Ph.Eur, BP, JPOral (solid dosage) products as a coating agent; tablet and capsule diluent and tablet binder. In oral liquid products as a viscosity-increasing agent.
MaltolUSP-NFOral (liquids) as a falvour and flavouring agent
MaltoseUSP-NF, JPOral products as a sweetening agent and tablet diluent
MannitolUSP-NF, Ph.Eur, BP, JPOral products as a diluent; plasticizer; sweetening agent; tablet and capsule diluent and a tonicity agent
Medium Chain TriglyceridesUSP-NF, Ph.Eur, BP, JPOral liquid and topical products Emulsifying agent; solvent; suspending agent; therapeutic agent. In parenteral products as an oleaginous carrier
MentholUSP-NF, Ph.Eur, BP, JPOral products as a flavouring agent
Menthyl AcetateUSP-NF, Ph.EurOral products as a flavouring agent
Methyl ParabenUSP-NF, Ph.Eur, BP, JPOral, topical and parenteral products as an antimicrobial preservative
MethylcelluloseUSP-NF, Ph.Eur, BP, JPOral and topical products as a coating agent; emulsifying agent; suspending agent; tablet and capsule disintegrant; tablet binder and viscosity-increasing agent.
Microcrystalline CelluloseUSP-NF, Ph.Eur, BP, JPOral products (tablets and capsules) as diluent, dry binder and disintegrant. In topical products as an adsorbent and suspending agent
Microcrystalline WaxUSP-NFTopical products as a stiffening agent. In oral products as a controlled-release agent (added to matrix tablets) and in polymer coatings
Monosodium GlutamateUSP-NFOral products as a buffering agent and a flavouring agent
Myristic AcidFCC, JPEOral and topical products as an emulsifying agent; skin penetrant and tablet and capsule lubricant
Natural Flavouring SubstancesFCCOral products as flavourings
Neohesperidin DihydrochloridePh.Eur, BPOral products as flavour enhancer and a sweetening agent
Oleic AcidUSP-NF, Ph.Eur, BPTopical products as a emulsifying agent and skin penetrant
Palmitic AcidUSP-NF, Ph.Eur, BPOral and topical products as an emulsifying agent; skin penetrant; and a tablet and capsule lubricant
Peanut OilUSP-NF, Ph.Eur, BP, JPParenteral products (IM) as an oleaginous vehicle. In topical products as a vehicle and solvent/carrier
PectinUSP-NFOral and topical products as an adsorbent; emulsifying agent; gelling agent; thickening agent and a stabilizing agent.
Phosphoric AcidUSP-NF, Ph.Eur, BPOral, topical and parenteral products as an acidifying agent
PolycarbophilUSP-NFTopical products as an emulsifying; suspending and thickening agent. In buccal, ophthalmic, nasal and vaginal applications as a bioadhesive material. In oral products as a controlled-release agent and tablet binder
Potassium MetabisulfiteUSP-NF, Ph.Eur, BPOral products as an antimicrobial preservative and antioxidant
Potassium AlginateUSP-NFOral and topical products as an emulsifying agent; stabilizing agent; suspending agent and thickening agent
Potassium AlumUSP-NF, Ph.Eur, BP, JPVacines as a protein precipitant and in mouth washes/gargles as an astringent
Potassium BenzoateUSP-NFOral products as an antimicrobial preservative. Also as a tablet and capsule lubricant
Potassium BicarbonateUSP-NF, Ph.Eur, BPOral products (effervescent) tablets as a source of carbon dioxide
Potassium CarbonateUSP-NF, Ph.Eur, BP, JPOral products as an alkalising agent
Potassium ChlorideUSP-NF, Ph.Eur, BP, JPParenteral and ophthalmic products as a tonicity agent
Potassium CitrateUSP-NF, Ph.Eur, BPOral products as a alkalising agent; buffering agent and sequestering agent
Potassium HydroxideUSP-NF, Ph.Eur, BPOral products as an alkalising agent
Potassium SorbateUSP-NF, Ph.Eur, BPOral products as an antimicrobial preservative
Potato StarchPh.Eur; BPOral products as a binder and disintegrating agent
Pregelatinised StarchUSP-NF, Ph.Eur, JPOral products as a filler, binder and disintegrating agent
Propionic AcidUSP-NFOral and topical products as an acidifying agent; antimicrobial preservative; antioxidant and esterifying agent.
Propyl GallateUSP-NF, Ph.Eur, BPOral and topical products as an antioxidant
Propyl ParabenUSP-NF, Ph.Eur, BPOral, topical and parenteral products as an antimicrobial preservative
Propylene GlycolUSP-NF, Ph.Eur, BPOral, topical and parenteral products as a viscosity modifier, solubiliser and plasticiser
Propylene Glycol AlginateUSP-NFOral and topical products as a solubilising, suspending and emulsifying agent. Also used in foods and cosmetics
Silicon DioxideUSP-NF, Ph.Eur, BPOral and topical products as glidants, anticaking and texturizing agent. Widely used in foods and cosmetics
SimethiconeUSP-NF, Ph.Eur, BPOral and topical products as emollient, oil vehicle and lubricant. Also as an antifoam
Sodium AcetateUSP-NF, Ph.Eur, BPOral, topical and parenteral products as an antimicrobial preservative, buffering agent and stabiliser
Sodium AscorbateUSP-NF, Ph.Eur, BPOral and parenteral products as an antioxidant and a source of vitamin C
Sodium BenzoateUSP-NF, Ph.Eur, BPOral, dental, parenteral, rectal and topical products as an antimicrobial preservative
Sodium BicarbonateUSP-NF, Ph.Eur, BPOral, topical, parenteral and ophthalmic products as an alkalising and therapeutic agent
Sodium CarbonateUSP-NF, Ph.Eur, BPOral, rectal, ophthalmic and parenteral products as a buffering and alkalising agent
Sodium CarboxymethylcelluloseUSP-NF, Ph.Eur, BP, JPOral products as a coating agent, binder and disintegrant. For topical products as a stabilizing agent; suspending agent; and viscosity-increasing agent
Sodium ChlorideUSP-NF, Ph.Eur, BPOral, ophthalmic, nasal, parenteral and topical products as a filler, diluent and tonicity agent
Sodium CitrateUSP-NF, Ph.Eur, BPOral, topical, ophthalmic and parenteral products as a buffering, alkalising and sequestering agent
Sodium GluconateUSP-NFOral products as a natural preservative, buffer and pH adjuster
Sodium LactateUSP-NF, Ph.Eur, BPParenteral, oral, topical products as an antimicrobial preservative, buffering agent, emulsifying agent and humectant
Sodium Lauryl SulfateUSP-NF, Ph.Eur, BPOral, topical, rectal & vaginal products as an anionic surfactant, emulsifying agent and tablet and capsule lubricant
Sodium MetabisulfiteUSP-NF, Ph.Eur, BPParenteral, ophthalmic, oral, rectal and topical products as a preservative and antioxidant
Sodium PhosphateUSP-NF, Ph.Eur, BPParenteral, oral, topical and ophthalmic products as a buffering agent
Sodium PropionateUSP-NF, Ph.Eur, BPOral products as a preservative
Sodium Stearyl FumarateUSP-NF, Ph.Eur, BPOral products as a lubricant
Sodium SulfiteUSP-NF, Ph.Eur, BPParenteral, ophthalmic, oral, rectal and topical products as a preservative and antioxidant
Sodium ThiosulphateUSP-NF, Ph.Eur, BPParenteral, ophthalmic, oral, rectal and topical products as an antioxidant
Sorbic AcidUSP-NF, Ph.Eur, BPParenteral, ophthalmic, oral, rectal and topical products as a preservative
Stearic AcidUSP-NF, Ph.Eur, BPOral and topical products as an emulsifying and solubilising agent, and tablet and capsule lubricant
SucroseUSP-NF, Ph.Eur, BPOral products as a confectionery base, coating agent, granulation binder, suspending agent, tablet and capsule binder, tablet and capsule filler, therapeutic agent, viscosity-increasing agent and sweetener
Sucrose OctaacetateUSP-NF, Ph.Eur, BPOral products as a bittering agent and alcohol denaturant
TagatoseUSP-NF, Ph.Eur, BPOral products as a sweetening agent
TalcUSP-NF, Ph.Eur, BPOral and topical products as an anticaking agent, glidants, tablet and capsule diluent and lubricant
Tapioca StarchUSP-NF, Ph.Eur, BPOral and topical products as a thickening agent, tablet and capsule diluent and disintegrating agent
Tartaric AcidUSP-NF, Ph.Eur, BPOral, topical and parenteral products as an acidifying agent, flavour enhancer and sequestrant
ThaumatinUSP-NF, Ph.Eur, BPOral products as a flavour enhancer and sweetening agent
ThymolUSP-NF, Ph.Eur, BPInhalation, oral and topical products as an antioxidant, antiseptic, disinfectant, flavouring and skin penetration enhancer
TragacanthUSP-NF, Ph.Eur, BPOral, buccal and sublingual products as a suspending and viscosity-increasing agent
TrehaloseUSP-NF, Ph.Eur, BPOral, inhalation and parenteral products as a flavour enhancer, humectant, stabiliser, sweetening agent, tablet diluent and thickening agent
Triethyl CitrateUSP-NF, Ph.Eur, BPOral products as a plasticiser and solvent
UreaUSP-NF, Ph.Eur, BPTopical products as a moisturiser
Vegetable Oil – HydrogenatedUSP-NF, Ph.Eur, BPOral products as a tablet and capsule lubricant and tablet binder
Vitamin E Polyethylene SuccinateUSP-NF, Ph.Eur, JPTopical and oral products as an absorption enhancer; antioxidant; emulsifying agent; granulation aid; ointment base; solubilizing agent; surfactant; suspending agent; and tablet binder
Waxy Maize StarchPh.Eur, USP-NFOral products (tablets and capsules) as a filler/diluent, binder and disintegrant
White BeeswaxBP, JP, Ph.Eur, USP-NFOral products (tablets) as a controlled-release agent. In topical products as a stabilizing agent (emulsions) and stiffening agent (creams)
Xanthan GumUSP-NF, Ph.Eur, JP, BPOral and topical products as a gelling agent; stabilizing agent; suspending agent; sustained-release agent and a viscosity-increasing agent
XylitolUSP-NF, Ph.Eur, BPOral products as a coating agent; diluent; emollient; humectant; sweetening agent; and a tablet and capsule diluent and tablet filler
Yellow BeeswaxBP, JP, Ph.Eur, USP-NFTopical products as a polishing agent; stabilizing agent and stiffening agent. In oral products as a polishing glaze for sugar coated tablets
ZeinUSP-NF, Ph.Eur, BPOral products as a coating agent; extended-release agent and tablet binder
Zinc AcetateUSP-NF, Ph.Eur, BPTopical products as an emollient; emulsion stabilizer; gelling agent; opacifier; stabilizing, agent
Zinc StearateUSP-NF, Ph.Eur, BPOral products (Tablets and capsules) as a lubricant


Is GRAS List regularly updated?

The GRAS List is constantly under review. A material on the list can indeed be removed and its status revoked by the FDA. This happened in the past when partially hydrogenated fats were removed from the list in 2015 by the FDA.


What is the SCOGS Database?

The SCOGS Database permits the public to find and read for themselves the different opinions and decisions made by the FDA and its experts (in reality, the data is limited to the period between 1972 and 1980) about the safety of over three hundred ingredients.

Click here to access the SCOGS Database.



So there you have it. Excipients that also have GRAS status essentially means that their use is not subject to pre-market review by the FDA for their intended use determined by an expert scientific committee.

The GRAS framework provides an additional safeguard for public welfare, by requiring manufacturers to provide information needed by regulators and consumers, regarding safety of ingredients added into consumer products.


Sources Used

To ensure our content is accurate and scientifically sound, Pharmacentral implements a strict referencing policy. We only use peer-reviewed studies and reputable academic sources and authors.

Personal opinions and anecdotes are not used.

  • T.G. Neltner, N.R. Kulkarni, H.M. Alger, M.V. Maffini, E.D. Bongard, N.D. Fortin, E.D. Olson, Navigating the U.S. Food Additive Regulatory Program, Comprehensive Reviews in Food Science and Food Safety, 10 (2011) 342-368.


Utilising Dynamic Dissolution Testing to Predict Gastrointestinal Behaviour of Modified Release Products

In-vitro dissolution tests that correlate with in vivo behaviour provide a better understanding of bioavailability while also permitting setting of a product’s acceptance criteria and formulation parameters. When developing oral modified release products, formulators often face challenges of selecting optimal test media and protocols with which to conduct such dissolution tests. Catch up in this webinar where we review the concept of dynamic dissolution testing and application to new formulation screening, assessment of inter/intra-subject variability of GI pH and effect on drug release, design of robust modified release formulations using physiologically relevant bicarbonate buffers and batch release testing and quality control.

Addressing Formulation Needs With a Different Technology: Say “Hello” to Ion Exchange Resins

Ion exchange is a solution for many formulation challenges, including modified release, taste masking of bitter drugs, improvement of solubility of poorly soluble APIs, and as an abuse deterrent. The different drug delivery systems that ion exchange can be used in is fairly diverse, which is one of the main attributes of the material. This Whitepaper discusses the utility of ion-exchange resins from Dow Chemical, widely known by their brand AMBERLITE™ and DUOLITE™. Click here to download this Whitepaper.

Benefits of Using High-Functionality Excipients in a Continuous Manufacturing Process

As pharmaceutical companies move increasingly toward changing production methods from batch to continuous processing, there is a need to re-evaluate the types and formulations of the excipients used. Within a continuous process, conventional monofunctional excipients must be added through individual feeders, potentially creating multiple sources of variability. In contrast, a single high-functionality co-processed excipient requires only one feeder, thus enhancing product performance while minimizing variability. This article discusses some benefits of continuous manufacturing and reports on the evaluation of a co-processed excipient composite comprising binder-filler, lubricant, superdisintegrant and glidant, used in tablet production. Click here to download this technical guide.

Benefits of Using High-Functionality Excipients in a Continuous Manufacturing Process PDF

Ingredient Spotlight – Disodium Edetate

As a pharmaceutical product formulator, you may have wondered what Disodium Edetate (also known as Sodium EDTA) is and how you can use it in your products. Given its ubiquity in pharmaceutical and other processing industries, these are not trivial questions, so kudos for wanting to familiarize yourself with its applications and limitations.

In simple terms, it is ethylenediaminetetraacetate as the disodium salt. It occurs as a white crystalline, odorless powder with a slightly acidic taste. According to the European Pharmacopoeia the pharmaceutical-grade material is required to contain NLT 99.0% and NMT 101.0% of C10H14N2Na2O8, calculated on a dried basis.


Chemical and physical particulars

Chemical Name: Ethylenediaminetetracetic acid, disodium salt

CAS Registry Number: [139-33-3]

Molecular weight: 336.2

Chemical formula and structure: [CH2N(CH2CO2H]2]2 Na2

Acidity/alkalinity: pH 4.3 – 4.7 (1% w/v solution)

Solubility: Soluble in water (1 in 11 parts)


Current Regulatory Status

Currently listed in the Ph.Eur, USP-NF, BP and JP. It is also GRAS listed and included in the FDA Inactive Ingredients Database (Inhalations, Injections, Ophthalmic preparations, Oral capsules, Solutions, Suspensions, Syrups and Tablets, Rectal, Topical and Vaginal preparations).

Dsodium edetate is poorly absorbed from the gastrointestinal tract and associated with few adverse effects when used as an excipient. In larger doses, however, disodium edetate (and other edetates) cause calcium depletion (hypocalcemia), especially when used over an extended period of time.

However, this material should he used with caution in patients with renal impairment, tuberculosis, and impaired cardiac function. The WHO has set an estimated acceptable daily intake in foodstuffs of up to 2.5 mg/kg body-weight.


Uses in Pharmaceutical Formulations

Disodium edetate is used in topical, oral, ophthalmic and parenteral pharmaceutical formulations as well as in cosmetic and food products as a chelating and sequestering agent of heavy metal cations. The typical concentrations are between 0.005 and 0.1% w/v.

Chelation and sequestration of metal cations helps to stabilise, clarify and protect a formulation in many different ways. For instance, Edetate enhances the action of preservatives and stabilizes antioxidants; stabilises and protects polymeric thickeners, colorants, flavours and fragrances; and prolongs action of antioxidants such Tocopherol and ascorbate, for instance, in fats and oils.

Therefore, add edetate disodium (or other suitable edentates) to products that have a flavour, fragrance, colorant, polymeric thickener e.g carbomer, hyaluronic acid and hydrocolloid gums, preservatives, antioxidants, antibiotics, local anaesthetics and certain vaccines.

Disodium edetate is also used therapeutically as an anticoagulant due to its ability to chelate calcium and prevent the coagulation of blood in vitro.


Useful Tips and Comments

Edetate salts are more stable than EDTA. However, disodium edetate dihydrate loses water of crystallization when heated to 120o C.

Disodium edetate is hygroscopic and is unstable when exposed to moisture. The stability of the metal—edetate complex is dependent on the metal ion involved and the pH.

Disodium edetate is incompatible with strong oxidizing agents, strong bases and metal ions.



Merck (Titriplex® II – EMPROVE® EXPERT PhEur, BP, USP, JP)


For a full description of this material, navigate to Disodium Edatate Monograph page.



[1] R.K. Evans, D.K. Nawrocki, L.A. Isopi, D.M. Williams, D.R. Casimiro, S. Chin, M. Chen, D.M. Zhu, J.W. Shiver, D.B. Volkin, Development of stable liquid formulations for adenovirus-based vaccines, J Pharm Sci, 93 (2004) 2458-2475.

[2] R.S. Lanigan, T.A. Yamarik, Final report on the safety assessment of EDTA, calcium disodium EDTA, diammonium EDTA, dipotassium EDTA, disodium EDTA, TEA-EDTA, tetrasodium EDTA, tripotassium EDTA, trisodium EDTA, HEDTA, and trisodium HEDTA, International journal of toxicology, 21 Suppl 2 (2002) 95-142.

[3] J. Wahr, J. Vender, H.C. Gilbert, B. Spiess, J.C. Horrow, R. Maddi, Effect of propofol with and without EDTA on haemodynamics and calcium and magnesium homeostasis during and after cardiac surgery, Intensive care medicine, 26 Suppl 4 (2000) S443-451.

Propylene glycol alginate

Propylene glycol alginate is a propylene glycol ester of alginic acid. Alginic acid is a naturally-occurring anionic polysaccharide obtained from algae. It is composed of a mixture of mannuronic acid and guloronic acid residues.

Propylene glycol alginate is a whitish fibrous powder, that is practically odourless and tasteless. It exhibits both cold and hot water solubility. It is available in different grades, corresponding to difference in viscosity: standard grades and high esterification grades.

The general chemical structure of Propylene glycol alginate is shown below:

Generalised Chemical Structure of Propylene glycol alginate


Current Regulatory Status

Propylene glycol alginate is listed in the USP-NF and approved for use in food in Europe (E405). A specification for propylene glycol alginate is contained in the Food Chemicals Codex (FCC) and the Japanese Pharmaceutical Excipients (JPE).

Propylene glycol alginate is included in the FDA Inactive Ingredients Database (oral preparations) and generally regarded as safe, nontoxic and non-irritant material, although excessive oral consumption may be harmful.


Applications in Pharmaceutical Formulations

Propylene glycol alginate is supplied in two types: standard and high esterification. Within each type are several grades having viscosities ranging from 50 to 600 mPa s.

The principal use of propylene glycol alginate is as a viscosity-increasing agent and thickener in topical and oral emulsions and suspensions. Higher viscosity grades are ideal for this application and are selected for the same reasons as sodium alginate but unlike sodium alginate propylene glycol alginate remains soluble at low pH and does not gel in the presence of polyvalent cations (e.g calcium).

Propylene glycol alginate exhibits surface active effects, enabling it to additionally function as an emulsion stabiliser, which distinguishes it from sodium alginate.

Propylene glycol alginate is also used as a binder and disintegrant in oral granules and tablets and can help enhance the rate of dissolution.

Owing to its mucoadhesive properties, propylene glycol alginate can be used to formulate lozenges, buccal, sublingual, nasal, ocular and other dosage forms that require extended residence times on mucosal surfaces.


Typical Uses of Propylene glycol alginate:

Use Concentration (%)
Thickener in creams 1 – 5
Stabiliser for emulsions and suspensions 1 – 2
Suspending agent 1 – 5
Capsule and tablet binder 1 – 3
Capsule and tablet disintegrant 3 – 10


Useful Tips and Comments

Propylene glycol alginate solutions are most stable at pH 3 – 6. In alkaline solutions, propylene glycol alginate is rapidly saponified. Please note that alginate solutions are susceptible to microbial spoilage and should be preserved with an antimicrobial preservative. Sterilization processes (e.g autoclaving) can adversely affect the viscosity of propylene glycol alginate solutions.






[1] W. Schmid, K.M. Picker-Freyer, Tableting and tablet properties of alginates: Characterisation and potential for Soft Tableting, European Journal of Pharmaceutics and Biopharmaceutics, 72 (2009) 165-172.

[2] Z. Shariatinia, Chapter 2 – Pharmaceutical applications of natural polysaccharides, in: M.S. Hasnain, A.K. Nayak (Eds.) Natural Polysaccharides in Drug Delivery and Biomedical Applications, Academic Press2019, pp. 15-57.

[3] J.N. BeMiller, 9 – Hydrocolloids, in: E.K. Arendt, F. Dal Bello (Eds.) Gluten-Free Cereal Products and Beverages, Academic Press, San Diego, 2008, pp. 203-215.


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