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An excipient is an inactive substance formulated alongside the active ingredient ("API") of a medication, for the purpose of bulking-up formulations that contain potent active ingredients (thus often referred to as "bulking agents," "fillers," or "diluents"). Bulking up allows convenient and accurate dispensation of a drug substance when producing a dosage form. They also can serve various therapeutic-enhancing purposes, such as facilitating drug absorption or solubility, or other pharmacokinetic considerations. Excipients can also be useful in the manufacturing process, to aid in the handling of the active substance concerned such as by facilitating powder flowability or non-stick properties, in addition to aiding in vitro stability such as prevention of denaturation over the expected shelf life. The selection of appropriate excipients also depends upon the route of administration and the dosage form, as well as the active ingredient and other factors.
Pharmaceutical regulations and standards require that all ingredients in drugs, as well as their chemical decomposition products, be identified and shown to be safe. As with new drug substances and dosage forms thereof, novel excipients themselves can be patented; sometimes, however, a particular formulation involving them is kept as a trade secret instead (if not easily reverse-engineered).
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 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:
- 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.
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.
Enterics control 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.
Examples of disintegrants include:
- Crosslinked polymers: crosslinked polyvinylpyrrolidone (crospovidone), crosslinked sodium carboxymethyl cellulose (croscarmellose sodium).
- The modified starch sodium starch glycolate.
Also sometimes called "bulking agents" or "diluents." Fillers add volume and/or mass to a drug substance, thereby facilitating precise metering and handling thereof in the preparation of dosage forms. Fillers typically also fill out the size of a tablet or capsule, making it practical to produce and convenient for the consumer to use.
A good filler should typically be inert, compatible with the other components of the formulation, non-hygroscopic, 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. Sometimes other noted kinds of excipients are in effect doubling in function as fillers.
Relatively new precision "micro-dosing" technologies have begun enabling small-scale production of drug products without the need for fillers (or any excipient, if desired - and if otherwise acceptable), due to its ability to handle and measure out appropriate quantities without bulking/dilution. Such technologies exist for dispensing both solid and non-solid substances, though powder is most common currently.
Flavours can 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, 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 are added to improve the appearance of a formulation. Colour consistency is important as it allows easy identification of a medication.
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. Lubricants are agents added in small quantities to tablet and capsule formulations to improve certain processing characteristics.
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 & 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:
- Generally poor lubricants, no glidant or anti-adherent properties.
- 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.
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.
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[disambiguation needed]
- Synthetic preservatives like the parabens: methyl paraben and propyl paraben.
- FDA database for Inactive Ingredient Search for Approved Drug Products
- Lesney, Mark S. (January 2001). "More than just the sugar in the pill". Today's Chemist at Work 10 (1): 30–36. ISSN 1532-4494. Archived from the original on August 13, 2013. Retrieved August 13, 2013.
- "Micro-dosing equipment fills niche in R&D, clinical trial materials, 2009". Tablets & Capsules (CSC Publishing). March 2009. ISSN 1938-9159.
- Mills, Simon (April 2007). "Excipients". Training Workshop on Pharmaceutical Development with focus on Paediatric Formulations. World Health Organization. Archived from the original on October 20, 2012.