Excipients are pharmacologically "inert" substances used as a carrier for the active ingredients of the medication in order to achieve a desired consistency or form for the manufacturing process. The term “excipients” comes from the Latin word “excipiens”, which means to receive, to gather, to take out. This refers to one of the property of an excipients, which is to ensure that a medicinal product has the weight, consistency and volume which is necessary for the correct administration of the drug to the patient.
In 1957, excipients were defined as ‘the substance used as a medium for giving a medicament’, that is to say with simply the functions of an inert support of the active principle or principles. Again, in 1974 they are described as ‘any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug: a vehicle’. According to the United States’ National Formulary (1994), an excipient is any substance other than the active drug, added intentionally to the medicinal formulation, or ‘everything in the formulation except the active drug’.
Excipients plays a vital role in a modern pharmaceutical dosage form, suitable to be administered enterally, parenterally and topically. They plays a key role in improving the stability, oraganoleptic properties, bioavailability and consequently the efficacy and tolerability of the medicinal drug. Excipients are obtained from different origin: animal (e.g. gelatin, stearic acid), plant (e.g. starches, cellulose), mineral (e.g. calcium phosphate, silica) and synthesis (e.g. PEGs, polysorbates, povidone, etc.). The origin and use of the excipients do not often guarantee the quality required by the pharmaceutical industry, therefore submit them to more thorough analytical controls.
A dietary supplement is also known as food supplement or nutritional supplement. These are the preparations anticipated to supplement the diet and provide the various nutrients, like vitamins, minerals, fibre, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet. According to the Congress in the Dietary Supplement Health and Education Act (DSHEA) (1994), a dietary supplement is a product taken by mouth that contains an ingredient intended to supplement the diet.
The dietary ingredients include vitamins, minerals, herbs and other botanicals; amino acids; and substances such as enzymes, organ tissues, glandulars and metabolites. Dietary supplements also obtained in form of extracts or concentrate and dispensed as tablets, capsules, soft gels, gelcaps, liquids and powders. Supplements containing vitamins or dietary minerals are included as a category of food in the Codex Alimentarius, a collection of internationally recognized standards, codes of practice, guidelines and other recommendations relating to foods, food production and food safety. Dietary supplements are available without a prescription through a number of retail outlets, including grocery stores, drug stores, general merchandise retailers, natural food stores and speciality health and nutrition stores.
Dietary supplements contains number of additional ingredients, these ingredients are fillers, binders, disintegrants, lubricants, colourants, sweeteners, flavouring agents and coating materials. Each product label does not always shows the presence of these agents. In fact, the label does not generally state that no fillers, sweeteners or disintegrants are used. Some causes like digestive upset, sensitivity or allergic reactions due to use dietary supplements.
Classification of excipients used in supplements
Source dependant classification:
- Animal (e.g. lactose, gelatin, stearic acid),
- Plant (e.g. starches, sugars, cellulose, arginates),
- Mineral (e.g. calcium phosphate, silica)
- Synthesis (e.g. PEGs, polysorbates, povidone, etc.)
Functional classification:
Binders: Added to help hold the particles together and give it strength to final dosage form eg. Polyvinyl Pyrrolidon-K, Hydorxy Ethyl Cellulose, Hydroxy Propyl Methyl Cellulose, starch paste etc.
Coating agent: May be functional or non-functional
Non functional coating agents: Hydroxy Propyl Methyl Cellulose -5 or 15 cps etc for film coating.
Functional Coating agent: SHELLAC, ZEIN, cellulose acetate pthalate etc for enteric coating.
Disintegrants: Used to promote the breakup of the immediate release dosage form e.g. Sodium CMC, Sodium starch glycolate, Crosspovidon, polyplasdon, Kollidon
Fillers and diluents: Fillers used to increase the bulk volume of and hardness of tablet e.g. MCC, Dicalcium phosphate, Lactose, Mannitol etc
Flavors: Commonly added to mouth dissolving tablet, liquid dosage forms, Antibiotic dosage, chewable tablet formulations to improve taste, texture, and overall palatability. e.g. Peppermint, Mix fruit flaver, Orange flavour etc.
Colours: All colouring agents must be approved and certified by FDA. Two forms of colours are used in tablet preparation – FD &C and D & C dyes.
Wetting agents: Play an important role as cleaning, wetting, dispersing, emulsifying, foaming and anti-foaming agents . A wetting agent is a chemical compound that reduces the surface tension of a liquid. e.g. Sodium lauryl sulfate
Acidifying agents, buffers, stabilizers: They are used to maintain condition such as acidic/basic/neutral pH in which drug is stable. e.g. Citric acid, Sodium citrate etc
Lubricants: Lubricants are agents added in small quantities and prevent the sticking of drug compounds against machine parts. e.g. Talc, vegetable stearin, magnesium stearate
Glidants: Added to powder to prevent interparticulate friction e.g. Fumed silica, talc, magnesium carbonate, colloidal silicon dioxide etc
Preservatives: Added to prevent microbial growth in formulation. e.g. Methyl paraben and propyl paraben etc.
Sweeteners: Mainly used for bitter drug formulations and also in liquid dosage form for children’s palatability. e.g. Saccharin, Sucrose, Aspartem etc.
Risks of supplements
Many dietary supplements contain active ingredients that can have strong effects on the body. Some supplements are beneficial while some of these products can pose unexpected risks. Substituting the prescribed medicines with dietary supplements or taking a combination of supplements with medicine could lead to harmful or even life-threatening results.
Especially before surgery if you are taking vitamins, minerals, botanicals and other products, it’s necessary to tell your health professional because some supplements can have unwanted effects before, during and after surgery. Dietary supplements are not intended to treat, diagnose, mitigate, prevent or cure disease.
Most commonly used excipients in supplements
Providone (Polyvinylpyrrolidone or PVP): PVP is a synthetic polymer considered to be a potential carcinogen. It is used as a suspending agent and dispersing agent most of encapsulated nutritional supplements.
Magnesium Stearate: Magnesium Stearate can be obtained from animal or vegetable sources. It is water insoluble lubricant reduces the absorption of nutrients as well as suppresses the immune system.
Maltodextrin: It is a refined sugar used as flavour, bulking agent and as a texturizer obtained by the hydrolysis of cornstarch. Free glutamate (MSG) containing maltodextrin is known as neurotoxin.
Silicon Dioxide: Silica is practically insoluble in water, tasteless and transparent powder. It is used as an absorbent and flow agent in supplements but it is a main component of beach sand.
Resin: Resins obtained from plant or synthetic origin includes polyvinyl, polystyrene and polyethylene. Resins are used in preparations of pharmaceuticals, synthetic plastics, lacquers, varnishes and inks. Resin Toxicity is dependent on the ingredients used in the manufacturing of resin.
Dicalcium Phosphate: It is a mineral complex of calcium and phosphorous used as a tableting aid, filler or bulking agent.
Polysorbates 80: It is a non-ionic surfactant used in pharmaceuticals as emulsifier and stabilizer also used in cosmetics and supplements. It is obtained by microbial fermentation of oleic acid, palmitic acid, sorbitol and ethylene oxide.
Titanium Dioxide: Titanium dioxide is a pro-oxidant, a white opaque pigment, inorganic in nature used in supplements as a whitening agent. It is also used in paints, plastic, paper, inks, fibres, food, coatings and cosmetics.
Polyethylene Glycol 3350: Polyethylene is a polymerized ethylene resin while glycol is a dihydric alcohol. It improves resistance moisture and oxidation used as emulsifier, binder and surfactant.
Shellac: It is also called as Pharmaceutical Glaze used to coat vitamin tablets. Shellac is difficult for the body to break down and assimilate.
Natural or Synthetic: Natural and synthetic nutrients contain exactly the same elements. But the elements are arranged in slightly different fashion in the molecular structure of synthetic nutrients. Synthesized nutrients are mirror-image duplicates of natural nutrients. E.g. Natural vitamin E is three times more absorbable than its synthetically obtained vitamins.
Regulations
Many drug manufacturers write various claims on the label of dietary supplements. Manufacturers cannot claim that their product will diagnose, cure, mitigate, treat or prevent a disease. Manufacturer is not been granted to claim regarding treatment, cure or prevention of any disease or diseased condition. Writing of these kinds of claims is illegal on any supplement. Also supplement products should not be mis-advertised through any media like television, newspaper, internet etc.
Three types of claims manufacturers can make:
- A health related claim: This claim gives interconnection of supplement and reduced health risk.
- Content related claim: This claim denotes amount of nutrient or compound in a supplement.
- Function related claim: This claim describes that in which manner supplement affects the body.
The best manufacturers provide you maximum information about the ingredients on the label. Does the product clearly mention about "Calcium...500mg" or does it provide specific information on the form of Magnesium provided, say "Calcium chloride" or "Calcium hydroxide" etc. If the label is not descriptive in nature about the form of the nutrient then discuss with your health professional before purchase of nutrient.
Details to be labelled on supplement products
- Name of the supplement product (Product name should depict the word supplement or should have written that product is a supplement.)
- Contents with quantity and if possible then with its caloric value
- Complete address of manufacturer, packer or distributor
- Usage & dosage directions
- Name of the plant if it’s from botanical source
- Total amount
- All excipients should be included if possible like fillers, binders, sweeteners, artificial colours, flavours etc.
- Cautionary information
Package insert is also to be provided along with product covering all sufficient information starting from ingredients to adverse effects and dosage/usage. As there are no strict criteria with the supplements compared to drug products in regard to regulatory aspects, it is an ethical responsibility of manufacturer to check its adverse effect before marketing. Products should be withdrawn if any illness or unsafe issues occur after consumption.
Regular "audits" are conducted by many ethical companies for their products (especially for the product manufactured from other manufacturer) to ensure label content claims and quality the product. The "Certificate of Analysis" is a company document which provides information about what was found in a specific product. Both certificates can be valid; certificate was issued by an in-house or from other laboratory.
The safe dietary supplement products which are not adulterated or misbranded, which have the identity and provide the quality of dietary ingredients declared on the label, and which meet the quality specification is the main objective of GMPs. GMPs contains all aspects of manufacture: personnel training, physical make-up of plant, sanitation of buildings and facilities, equipment used in manufacture; production and processing controls, warehousing, and distribution procedures.
Use of excipients in a limited amount for supplements may definitely serve as an ideal tool for the patient. Risk factors of crucial excipients have to be considered during formulation of supplements. There should be proper labelling on the supplement product and literature along with product can be a key factor for the usage of supplements. Finally regulatory aspects, though not stringent, should be monitored during development and manufacturing. Resolving all these matters in a suitable way will definitely lead to safe and effective use of supplements.
The author is Professor in Pharmacy and Dean,
Faculty ofTechnology & Engineering,
The Maharaja Sayajirao University of Baroda, Vadodara
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