Excipient

An excipient is a substance formulated alongside theactive ingredientof amedication.They may be used to enhance the active ingredient’s therapeutic properties; to facilitate drug absorption; to reduce viscosity; to enhance solubility; to improve long-term stabilization (preventing denaturation and aggregation during the expected shelf life); or to add bulk to solid formulations that have small amounts of potent active ingredients (in that context, they are often referred to as "bulking agents", "fillers", or "diluents" ).During the manufacturing process, excipients can improve the handling of active substances and facilitate powder flow. The choice of excipients depends on factors such as the intended route of administration, the dosage form, and compatibility with the active ingredient.

Virtually all marketed drugs contain excipients, and final drug formulations commonly contain more excipient than active ingredient. Pharmaceutical regulations and standards mandate the identification and safety assessment of all ingredients in drugs, including their chemical decomposition products. Novel excipients can sometimes be patented, or the specific formulation can be kept as atrade secretto prevent competitors from duplicating it throughreverse engineering.

Relative versus absolute inactivity

Though excipients were at one time assumed to be "inactive" ingredients, it is now understood that they can sometimes be "a key determinant of dosage form performance";in other words, their effects onpharmacodynamicsandpharmacokinetics,although usually negligible, cannot beknownto be negligible withoutempirical confirmationand sometimes are important. For that reason, inbasic researchandclinical trialsthey are sometimes included in thecontrol substancesin order to minimizeconfounding,reflecting that otherwise, the absence of the active ingredient would not be the only variable involved, because absence of excipient cannot always be assumed not to be a variable.Such studies are called excipient-controlled orvehicle-controlled studies.

Types

Adjuvants

Main article:Immunologic adjuvant

Adjuvants are added to vaccines to enhance or modify the immune system response to an immunization. An adjuvant may stimulate the immune system to respond more vigorously to a vaccine, which leads to more robust immunity in the recipient.

Antiadherents

Antiadherents reduce theadhesionbetween thepowder(granules) and thepunchfaces and thus prevent sticking to tablet punches by offering anon-stick surface.They are also used to help protect tablets from sticking. The most commonly used ismagnesium stearate.

Binders

Binders hold the ingredients in a tablet together. Binders ensure that tablets and granules can be formed with required mechanical strength, and give volume to low active dose tablets. Binders are usually:

• Saccharidesand their derivatives:
  • Disaccharides:sucrose,lactose;
  • Polysaccharidesand their derivatives:starches,celluloseor modified cellulose such asmicrocrystalline celluloseandcellulose etherssuch ashydroxypropyl cellulose(HPC);
  • Sugar alcoholssuch asxylitol,sorbitolormannitol;
• Protein:gelatin;
• Syntheticpolymers:polyvinylpyrrolidone(PVP),polyethylene glycol(PEG)...

Binders are classified according to their application:

• Solution binders are dissolved in a solvent (for examplewateroralcoholcan be used in wet granulation processes). Examples include gelatin, cellulose, cellulose derivatives, polyvinylpyrrolidone, starch, sucrose and polyethylene glycol.
• Dry binders are added to the powder blend, either after a wet granulation step, or as part of a direct powder compression (DC) formula. Examples include cellulose, methyl cellulose, polyvinylpyrrolidone and polyethylene glycol.

Coatings

Tablet coatings protect tablet ingredients from deterioration by moisture in the air and make large or unpleasant-tasting tablets easier to swallow. For most coated tablets, a cellulose etherhydroxypropyl methylcellulose(HPMC) film coating is used which is free of sugar and potentialallergens.Occasionally, other coating materials are used, for example synthetic polymers,shellac,corn proteinzeinor other polysaccharides.Capsulesare coated with gelatin.

Entericscontrol the rate of drug release and determine where the drug will be released in the digestive tract. Materials used for enteric coatings include fatty acids, waxes, shellac, plastics, and plant fibers.

Colours

Coloursare added to improve the appearance of a formulation. Colour consistency is important as it allows easy identification of a medication. Furthermore, colours often improve the aesthetic look and feel of medications. Small amounts of colouring agents are easily processed by the body, although rare reactions are known, notably totartrazine.Commonly, titanium oxide is used as a colouring agent to produce the popular opaque colours along with azo dyes for other colors. By increasing theseorganolepticproperties a patient is more likely to adhere to their schedule and therapeutic objectives will also have a better outcome for the patient especially children.

Disintegrants

Disintegrants expand and dissolve when wet causing the tablet to break apart in thedigestive tract,or in specific segments of the digestion process, releasing the active ingredients forabsorption.They ensure that when the tablet is in contact withwater,it rapidly breaks down into smaller fragments, facilitatingdissolution.

Examples of disintegrants include:

• Crosslinked polymers: crosslinkedpolyvinylpyrrolidone(crospovidone), crosslinked sodiumcarboxymethyl cellulose(croscarmellose sodium).
• sodium starch glycolate,amodified starch

Flavours

Flavourscan be used to mask unpleasant tasting active ingredients and improve the acceptance that the patient will complete a course of medication. Flavourings may be natural (e.g. fruit extract) or artificial.

For example, to improve:

• a bitter product–mint,cherryoranisemay be used
• a salty product–peach,apricotorliquoricemay be used
• a sour product–raspberryor liquorice may be used
• an excessively sweet product–vanillamay be used

Glidants

Glidantsare used to promote powder flow by reducing interparticle friction and cohesion. These are used in combination with lubricants as they have no ability to reduce wall friction. Examples includesilica gel,fumed silica,talc,andmagnesium carbonate.However, some silica gel glidants such as Syloid(R) 244 FP and Syloid(R) XDP are multi-functional and offer several other performance benefits in addition to reducing interparticle friction including moisture resistance, taste, marketing, etc.

Lubricants

Lubricantsprevent ingredients from clumping together and from sticking to the tablet punches or capsule filling machine. Lubricants also ensure that tablet formation and ejection can occur with lowfrictionbetween the solid and die wall.

Common minerals liketalcorsilica,andfats,e.g. vegetablestearin,magnesium stearateorstearic acidare the most frequently used lubricants in tablets or hard gelatin capsules. Lubricants are agents added in small quantities to tablet and capsule formulations to improve certain processing characteristics. While lubricants are often added to improve manufacturability of the drug products, it may also negatively impact the product quality. For example, extended mi xing of lubricants during blending may results in delayed dissolution and softer tablets, which is often referred to as "over-lubrication". Therefore, optimizing lubrication time is critical during pharmaceutical development.

There are three roles identified with lubricants as follows:

• True lubricant role:

To decrease friction at the interface between a tablet’s surface and the die wall during ejection and reduce wear on punches and dies.

• Anti-adherent role:

Prevent sticking to punch faces or in the case of encapsulation, lubricants.

Prevent sticking to machine dosators, tamping pins, etc.

• Glidant role:

Enhance product flow by reducing interparticulate friction.

There are two major types of lubricants:

• Hydrophilic

Generally poor lubricants, no glidant or anti-adherent properties.

• Hydrophobic

Most widely used lubricants in use today are of the hydrophobic category. Hydrophobic lubricants are generally good lubricants and are usually effective at relatively low concentrations. Many also have both anti-adherent and glidant properties. For these reasons, hydrophobic lubricants are used much more frequently than hydrophilic compounds. Examples include magnesium stearate.

Preservatives

Some typicalpreservativesused in pharmaceutical formulations are

• Antioxidantslikevitamin A,vitamin E,vitamin C,retinyl palmitate,andselenium
• Theamino acidscysteineandmethionine
• Citric acidandsodium citrate
• Synthetic preservatives like theparabens:methyl parabenandpropyl paraben.

Sorbents

Sorbentsare used for tablet/capsule moisture-proofing by limited fluid sorbing (taking up of a liquid or a gas either byadsorptionor byabsorption) in a dry state. For example,desiccantsabsorb water,dryingout (desiccating) the surrounding materials.

Sweeteners

Sweetenersare added to make the ingredients more palatable, especially in chewable tablets such asantacidor liquids likecough syrup.Sugarcan be used to mask unpleasant tastes or smells, but artificial sweeteners tend to be preferred, as natural ones tend to cause tooth decay.

Vehicles

In liquid and gel formulations, the bulk excipient that serves as a medium for conveying the active ingredient is usually called thevehicle.Petrolatum,dimethyl sulfoxideandmineral oilare common vehicles.

See also

• Active ingredient
• Pharmaceutics
• Pharmacology
• Placebo
• Placebo effect
• Quality system

External links

• FDA database for Inactive Ingredient Search for Approved Drug Products
• Excipient selection for injectable / parenteral formulations
• IPEC-Americas
• UCSF-CERSI Excipient Browser