If you read enough supplement advertisements, like I do, you’ll often see the purity of a product is cited as one of its merits. It’s usually some phrase like:
Contains no binders! No fillers! No colours! No excipients! No starch! No gluten! No coatings! No flow agents!
It’s a point of pride for supplement manufacturers to advertise that their product contains nothing but the labelled ingredient. And that’s also seen as an important benefit to many that purchase supplements. The perception from many consumers (based on my personal experience) seems to be that products are inferior if they contain non-drug ingredients. By this measure, drug products are problematic. Pharmaceuticals all contain an array of binders, coatings, supplements and fillers. Even (gasp) artificial ingredients and sweeteners! And they’re often, though not always, disclosed on the package label.
But rather than being a negative feature, these supplementary, non-medicinal ingredients play a critical role in ensuring that drug products are of consistent and reproducible quality. Without them, we’d have products that are potentially unstable, we’d be unclear if they were actually being absorbed, and we wouldn’t know if they actually delivered any active ingredients into the body. In short, we’d be in the same situation we’re currently in with many herbal remedies and other types of supplements.
Standard pharmaceutical products are evaluated in both clinical trials (to measure efficacy) but also more basic tests – such as whether a drug that is ingested is actually absorbed into the bloodstream. A promising drug won’t work if it doesn’t reach the desired site of action. And to do that, we use a variety of tools and processes to ensure that a drug is reliably and predictably absorbed when we use it, whether by ingesting it, rubbing it on our skin, or injecting it. Excipients can be described as any components of a drug product that are not the “API”, the active pharmaceutical ingredient. Excipients serve to keep the API stable, help its absorption, and simplify the manufacturing process.They help ensure that products are consistent – batch to batch and bottle to bottle. Excipients also help improve consumer acceptance and usage.
It took me some time as a pharmacist before I realized why supplement manufacturers strive to minimize the use of excipents in their products. It’s because the consistency, absorption and effectiveness of most products hasn’t been measured, and doesn’t need to be evaluated. That is, there’s no testing done to see if the product is absorbed consistently. You can’t control what you don’t know, and with the majority of herbal products, there’s no standardization of the active ingredient – because it may not even be clear what the active ingredients actually are. So any attempt to produce a consistent product is complicated by the lack of an API, and not knowing what type of product consistency is needed.
I’m asked about excipients regularly. There are hundreds in use, and their presence can be confusing to consumers, who may not understand their role. Patients may also have personal concerns about a specific type of excipient, or may need to avoid specific substances due to allergies. Here are some of the inactive ingredients you may see listed on on a package’s label – and why they’re there:
To make dosage forms a reasonable size, bulk materials are added to give size to finished products. (Imagine the size of a 100 microgram tablet without any fillers). Bulk materials also ease processing and manufacturing. They may influence the flow of the material during manufacturing, and can impact on the final product’s stability. Typical fillers for tablets and capsules include starch, calcium salts, and sugars like lactose. In liquid formulations, materials like glycerine and water are used to dissolve (or suspend) active ingredients and simplify dose measurements. Alcohol, a historically popular diluent, is now rarely used. Topical products like creams and lotions use fillers like mineral oil, petrolatum, lanolin and various waxes.
Lactose is a common filler and sweetener (see below) in many prescription and non-prescription drugs. While intolerance is possible, the small amounts in most drugs makes the risk minimal.
Coatings and Disintegrants
Once the dosage form is consumed, we want it to dissolve in a consistent manner. Products that don’t dissolve are not absorbed. Disintegrants break up a tablet or capsule at the appropriate time. Most orally consumed APIs are stable in stomach acid and disintegrate within a few minutes of ingestion. Some can be absorbed under the tongue, so disintegrating agents ensure that products like nitroglycerine dissolve immediately upon contact with saliva. Common disintegrating agents include alginic acid, microcrystalline cellulose, and various forms of starch.
Coatings provide protection of the final product from light, oxygen, and moisture. Coatings can include gluten, (food grade) shellac, and gelatin. Some drugs are destroyed by stomach acid, so a combination of coatings and disintegrants ensure they dissolve late, after the intact tablet has passed into the small intestine, a less acidic environement. Acid-resistant (“enteric”) coatings, like cellulose acetate phthalate, work this way. That’s why some products must not be crushed or chewed before swallowing: The active ingredient would otherwise be destroyed by stomach acid.
Lubricants are incorporated into dosage forms to support the manufacturing process. They can reduce static charges, and ease the flow of the powder form, ensuring products will have a consistent content of the API per unit. Lubricants impact on the dissolution of the final dosage form, affecting the absorbtion rate and extent. Lubricants include calcium and magnesium stearate, polyethylene glycol, stearic acid, and talc.
Sweeteners and Flavoring Agents
Sweetener products and flavoring agents make final products palatable. If you’ve ever tried to give a child a foul-tasting medication, you already have an appreciation of palatability. Palatability means that people will take their medication – a basic yet critical component of science-based medicine. In solid oral products, like tablets, sweeteners and flavors may coat tablets. In liquid products, like syrups and suspensions, sweeteners include sugars, artificial sweeteners, and products like corn syrup. Natural sweeteners are generally less popular from a manufacturing perspective, because of their association with dental caries, and possible impact on diabetics. Flavoring agents can be naturally-sourced or synthetically created. There is no intrinsic advantage to a natural sweetener or flavoring agent – it’s the physical characteristics that are important, not its origin.
Colours help with product identification and are also used for consistency with flavors, particularly in children’s formulations. (Though I truly didn’t appreciate the “dye-free” versions until I had a mouthful of a medication sprayed on me by an unhappy child.) In general, children and adults have no problems with the tiny amounts of dyes and colors in pharmaceutical products, though reactions have been reported, particularly with the product tartrazine.
Preservatives can stabilize the active ingredient or ensure a product remains sterile, which is a concern with all injectables and aqueous (water-based) products. Thimerosal needs no introduction to SBM readers. It’s a vaccine preservative. Benzalkonium chloride is a common preservative in contact lens products.
Allergies to Excipients
Adverse reactions and allergies can occur to both medicinal and non-medicinal ingredients. Severe allergic reactions have been attributed to trace amounts of corn in a dosage form [PDF], for example. The management of allergic reactions involves closely checking all excipients (and their sources), and isolating the causative agent (if possible). It can take a lot of digging, and sometimes even specialized pharmacy compounding, to deal with severe allergies and intolerances to commonly-used excipients.
The Product Expiry Date
Expiry dates for products are based on when a product’s finished quality standards (e.g., strength, quality, purity) are no longer met. That is, when product degradation progresses to a point where the product either lacks the labelled potency (most cases) or in some cases, has degraded into compounds that may be toxic. Chemicals can deteriorate for reasons that include chemical reactions, such as oxidation (usually from exposure to air or moisture), physical changes (e.g., separation of a suspension), photochemical reactions (i.e., light exposure) and even chemical reactions with the product packaging. Quantitative analysis of newly prepared products is done, usually in the final packaging, to understand how quickly a product will deteriorate, and the expiry date is established based on this information. This can be an iterative process – the final product formulation may change to make a product more stable. Or the packaging may change to give the finished product a longer shelf-life. Multiple factors can play a role.
Excipients play an important role in ensuring that medications are consistently absorbed and reproducible in their effects. Consumers should be reassured that their inclusion actually improves, rather than detracts from, the quality of the finished product.