Excipient
An excipient is a substance formulated alongside the active ingredient of a medication, included for the purpose of long-term stabilization, bulking up solid formulations that contain potent active ingredients in small amounts, or to confer a therapeutic enhancement on the active ingredient in the final dosage form, such as facilitating drug absorption, reducing viscosity, or enhancing solubility. Excipients can also be useful in the manufacturing process, to aid in the handling of the active substance concerns such as by facilitating powder flowability or non-stick properties, in addition to aiding in vitro stability such as prevention of denaturation or aggregation 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. A comprehensive classification system based on structure-property-application relationships has been proposed for excipients used in parenteral medications.
Pharmaceutical regulations and standards require that all ingredients in drugs, as well as their chemical decomposition products, be identified and shown to be safe. Often, more excipient is found in a final drug formulation than active ingredient, and practically all marketed drugs contain excipients. 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.
The Excipients Industry Forum as a multi stake-holder forum and information hub for the wider excipients industry and the public. Its goal is to promote open dialogue and partnership between the public, policy makers and the pharmaceutical industry.
The Federation of International Pharmaceutical Excipients Council, a pharmaceutical regulatory non-profit, develops, implements, and promotes global use of appropriate quality, safety, and functionality standards for pharmaceutical excipients and excipient delivery systems. IPEC-Americas, along with its counterparts in Europe, China, and Japan serves as a primary international resource on excipients for its members, governments, and public audiences. IPEC works in collaboration with ExcipientFest to present topics ranging from regulatory affairs to research and development, often featuring speakers from FDA and other pharmaceutical organizations.
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 on pharmacodynamics and pharmacokinetics, although usually negligible, cannot be known to be negligible without empirical confirmation and sometimes are important. For that reason, in basic research and clinical trials they are sometimes included in the control substances in order to minimize confounding, 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 or vehicle-controlled studies.Types
Antiadherents
Antiadherents reduce the adhesion between the powder and the punch faces and thus prevent sticking to tablet punches by offering a non-stick surface. They are also used to help protect tablets from sticking. The 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 ;
- * Sugar alcohols such as xylitol, sorbitol or mannitol;
- Protein: gelatin;
- Synthetic polymers: polyvinylpyrrolidone, polyethylene glycol...
- Solution binders are dissolved in a solvent. 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 formula. Examples include cellulose, methyl cellulose, polyvinylpyrrolidone and polyethylene glycol.
Coatings
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.
Colors
are added to improve the appearance of a formulation. Color consistency is important as it allows easy identification of a medication. Furthermore, colors often improve the aesthetic look and feel of medications. Small amounts of coloring agents are easily processed by the body, although rare reactions are known, notably to tartrazine. Commonly, titanium oxide is used as a coloring agent to produce the popular opaque colors along with azo dyes for other colors. By increasing these organoleptic properties 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 the digestive tract, or in specific segments of the digestion process, releasing the active ingredients for absorption. 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, crosslinked sodium carboxymethyl cellulose.
- The modified starch sodium starch glycolate.
Flavors
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
Glidants
Lubricants
s 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. While lubricants are often added to improve manufacturability of the drug products, it may also negatively impact the product quality. For example, extended mixing 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:
- Anti-adherent role:
- Glidant role:
- Hydrophilic
- Hydrophobic
Preservatives
- 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