Excipient

An excipient is generally a pharmacologically inactive substance used as a carrier for the active ingredients of a medication. In many cases, an "active" substance (such as acetylsalicylic acid) may not be easily administered and absorbed by the human body; in such cases the substance in question may be dissolved into or mixed with an excipient. Excipients are also sometimes used to bulk up formulations that contain very potent active ingredients, to allow for convenient and accurate dosage. In addition to their use in the single-dosage quantity, excipients can be used in the manufacturing process to aid in the handling of the active substance concerned. Depending on the route of administration, and form of medication, different excipients may be used. For oral administration tablets and capsules are used. Suppositories are used for rectal administration.

Often, once an active ingredient has been purified, it cannot stay in purified form for long. In many cases it will denature, fall out of solution, or stick to the sides of the container. To stabilize the active ingredient, excipients are added, ensuring that the active ingredient stays "active", and, just as importantly, stable for a sufficiently long period of time that the shelf-life of the product makes it competitive with other products. Thus, the formulation of excipients in many cases is considered a trade secret.

Pharmaceutical codes require that all ingredients in drugs, as well as their chemical decomposition products are identified and guaranteed to be safe. For this reason, excipients are only used when absolutely necessary and in the smallest amounts possible.

Types of excipients

Antiadherents

Antiadherents are used to reduce the adhesion between the powder (granules) and the punch faces and thus prevent sticking to tablet punches. They are also used to help protect tablets from sticking. Most commonly used is magnesium 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:

• Saccharides and their derivatives:
  • Disaccharides: sucrose, lactose;
  • Polysaccharides and their derivatives: starches, cellulose or modified cellulose such as microcrystalline cellulose and cellulose ethers such as hydroxypropyl cellulose (HPC);
  • Sugar alcohols such as xylitol, sorbitol or maltitol;
• Protein: gelatin;
• Synthetic polymers: polyvinylpyrrolidone (PVP), polyethylene glycol (PEG)...

Binders are classified according to their application:

• Solution binders are dissolved in a solvent (for example water or alcohol can 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 ether hydroxypropyl methylcellulose (HPMC) film coating is used which is free of sugar and potential allergens. Occasionally, other coating materials are used, for example synthetic polymers, shellac, corn protein zein or other polysaccharides. Capsules are coated with gelatin.

Changing the dissolution rates of active species

Enteric coatings control the rate of drug release and determine where the drug will be released in the digestive tract

Disintegrants

Disintegrants expand and dissolve when wet causing the tablet to break apart in the digestive tract, releasing the active ingredients for absorption. Disintegrant types include:

• Water uptake facilitators
• Tablet rupture promoters

They ensure that when the tablet is in contact with water, it rapidly breaks down into smaller fragments, facilitating dissolution.

Examples of disintegrants include:

• Crosslinked polymers: crosslinked polyvinylpyrrolidone (crospovidone), crosslinked sodium carboxymethyl cellulose (croscarmellose sodium).
• The modified starch sodium starch glycolate...

Fillers and diluents

Fillers fill out the size of a tablet or capsule, making it practical to produce and convenient for the consumer to use. By increasing the bulk volume, the fillers make it possible for the final product to have the proper volume for patient handling.

A good filler must be inert, compatible with the other components of the formulation, non-hygroscopic, soluble, relatively cheap, compactible, and preferably tasteless or pleasant tasting.

Plant cellulose (pure plant filler) is a popular filler in tablets or hard gelatin capsules. Dibasic calcium phosphate is another popular tablet filler. A range of vegetable fats and oils can be used in soft gelatin capsules.

Other examples of fillers include: lactose, sucrose, glucose, mannitol, sorbitol, calcium carbonate, and magnesium stearate.

Flavours

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

For example, to improve:

-a bitter product - mint, cherry or anise may be used

-a salty product - peach, apricot or liquorice may be used

-a sour product - raspberry or liquorice may be used

-an excessively sweet product - vanilla may be used

Colours

Colours are added to improve the appearance of a formulation. Colour consistency is important as it allows easy identification of a medication.

Lubricants

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

Common minerals like talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid are the most frequently used lubricants in tablets or hard gelatin capsules.

Glidants

Glidants are used to promote powder flow by reducing interparticle friction and cohesion. These are used in combination with lubricants as they have no ability to reduce die wall friction. Examples include fumed silica, talc, and magnesium carbonate.

Preservatives

Some typical preservatives used in pharmaceutical formulations are

• Antioxidants like vitamin A, vitamin E, vitamin C, retinyl palmitate, and selenium
• The amino acids cysteine and methionine
• Citric acid and sodium citrate
• Synthetic preservatives like the parabens: methyl paraben and propyl paraben.

Sorbents

Sorbents are used for tablet/capsule moisture-proofing by limited fluid sorbing (taking up of a liquid or a gas either by adsorption or by absorption) in a dry state.

Sweeteners

Sweeteners are added to make the ingredients more palatable, especially in chewable tablets such as antacid or liquids like cough syrup. Therefore, tooth decay is sometimes associated with cough syrup abuse. Sugar can be used to disguise unpleasant tastes or smells.

See also

• Pharmaceutics
• Active ingredient
• Pharmacology - Placebo - Placebo effect - Quality system
• Gluten-free diet

External links

• FDA inactive ingredient database
• International Pharmaceutical Excipients Council

References

ca:Excipient