According to the Dietary Supplement Health and Education Act of 1994 (DSHEA), a dietary supplement is defined as a product that is intended to be taken by mouth, in forms such as a tablet, capsule, powder, softgel, gelcap or liquid. Dosage forms are classified in one of two basic ways: 1) the physical state of the ingredient (solid, liquid or gas), or 2) by route of administration (ROA) pathway into the body. Generally, the ROA forms are: enteral (oral, buccal, sublingual and rectal), topical (transdermal), parenteral, inhaled (nasal), vaginal, ophthalmic and otic. Essentially, dietary supplements are designated as enteral orally ingested dosage forms. Many choices and types of oral dosage forms are available. Each of these solid-dosage forms has advantages and disadvantages.
Choice of a Delivery Form
Consumers have many more choices of dosage forms available these days. Solid dose (tablets/capsules) is still the major oral dosage form sold; however, preferences for other dosage forms continue to grow. Consumers’ preferences include: 1) ease of handling and swallowing, 2) speed of action, 3) gentleness on the stomach, and 4) perceptions of the therapeutic benefit. Clearly, the difficulties swallowing tablets or capsules is an issue experienced by a wide range of people regardless of age or gender, with the elderly and young having the most difficulty. More user-friendly dosage forms are now available: chewable tablets, effervescent, lozenges, gummies, powders, liquids and softgels.
Ideally, the key consideration in choosing an oral dosage form is in using one that serves as the optimal vehicle for both metabolic purposes and for maintaining efficacy of the product. Of the oral dosage forms available, tablets and capsules are probably the most well-known and therefore the default choice for healthcare companies. However, marketers are looking for other dosage forms to provide product differentiation, improve product compliance, and give options to their customers. There is a learning curve with these novel dosage forms in terms of product stability, ingredient interaction, supply chain considerations, and overall efficacy of the product.
The selection choice should be based on a consideration of several factors, including functionality (absorption, bioavailability and stability), suitability of ingredients (chemical, form, physical, pH, solubility, etc.) availability of ingredients/excipients, costs involved, and marketing preferences. Some other key considerations are minimal dosage administration frequency, minimal and preferred excipients, convenience and transportability.
A tablet is a compressed solid dosage form containing medicinal or beneficial substances with or without suitable binders or excipients. It may vary in shape, size and weight (i.e., round, oval, oblong, square or wafer). The term (tablet) comes from the French word tablette (little table), and is also sometimes referred to as a “pill." They also come in many forms: soft (chewable), effervescent, lozenge (pastille), multi-layered, control-release (slow-release) and orally disintegrating (quick-dissolve). Further, many of these can be uncoated or coated (film, sugar or enteric).
Buccal and sublingual tablets have had issues with some regulatory experts. Since they do not technically get ingested (absorption occurs in the mouth), some have argued they are not “ingested" oral dosage forms (which are listed above as being “eaten" or “taken by mouth.")
Advantages of tablets: 1) compactness of dosage, 2) high level of consumer acceptability/compliance/convenience, 3) easy to swallow (with proper coating), 4) good physical and chemical stability, 5) usually tasteless, 6) can be formulated for controlled release, and 7) economical to produce.
Disadvantages of tablets: 1) may need a liquid to take a dose, 2) difficult to adjust an exact dose, 3) may be hard to swallow for children or elders, 4) impossible for unconscious patients to consume, 5) not immediate releasethere’s a time delay for dissolution and absorption into the bloodstream, and 6) depending on formula, they may require more excipients to manufacture versus other dosage forms.
Hard-Shell Capsules: A capsule is a solid dosage form in a two-piece gelatin or vegetarian container (shell). Normally used for dry, powdered ingredients and non-aqueous liquids. Capsules typically can be coated, banded or enteric.
Advantages of capsules: 1) formulated to give an exact dose, 2) high level of consumer acceptability/compliance/convenience, 3) usually tasteless, 4) generally masks taste and odor of ingredients, and 5) typically easier to swallow than tablets.
Disadvantages of capsules: 1) may need a liquid to take dose, 2) difficult to adjust dose, 3) impossible for unconscious patients to consume, 4) time delay for dissolution and absorption into the bloodstream, 5) volume constraints due to the set size of capsules, and 6) not suitable for aqueous or hydroalcoholic liquids.
Softgel Capsules: Softgels are a liquid-filled dosage form. Primarily non-aqueous liquids (lipids, polyethylene glycol [PEGs], etc.) are used as an oil fill or to suspend powder ingredients; a great non-aqueous dosage form for oils or oil-based ingredients. The shell can be composed of gelatin (bovine, porcine or piscine) or non-animal (starches, carrageenan, etc.). They can be coated or enteric coated.
Advantages of softgels: 1) can handle up to 50 percent powders, 2) faster rate of absorption and better bioavailability, 3) high level of consumer acceptability/compliance/convenience, 4) formulated to give an exact dose, 5) convenient to carry, 6) masks taste and odor of ingredients, and 7) protects contents from oxidation and degradation.
Disadvantages of softgels: 1) not for high doses of powders, 2) hard to use for deliquescent/hydroscopic materials, 3) efflorescent materials cannot be used, 4) sensitive to heat and humidity (although vegetarian softgels are more stable in higher heat and humidity environments), 5) production of soft capsules is not as fast as for tablets or hard shell capsules, 6) typically minimum order quantities (MOQ) for softgels is higher than tablets or hard shell capsules.
Both hard or soft capsules can be modified-release capsules (including delayed-release capsules [gastro-resistant/enteric capsules] and sustained-release capsules [extended-/prolonged-release capsules]).
A solid dosage form that allows for multi-dose preparations consisting of solid, loose, dry particles of varying degrees of fineness. Powders can contain one or more active ingredients, with or without excipients and, if necessary, coloring matter and flavoring, and they can be effervescent.
Advantages of powders: 1) allows for easier dosage adjustments, 2) easier to swallow, particularly for children/elderly, 3) onset of action is faster than solid dosage forms, 4) can handle large dosing of materials, and 5) economical to produce.
Disadvantages of powders: 1) must be mixed into a liquid to swallow, 2) difficult to mask bad taste or odors, 3) not compatible with hygroscopic, oxidizing and deliquescent materials, 4) potential for dosage inaccuracy, and 5) inconvenient to travel with.
Oral Solutions: Oral solutions are a clear, homogeneous liquid dosage form that contains one or more chemical substances dissolved in a liquid solvent or mixture of mutually miscible solvents (aqueous or non-aqueous solvents).
Oral Emulsions (liquid in liquid dispersion): Oral emulsion is a two-phase system involving one liquid in a second liquid with which the first will not mix in the second (oil in water or water in oil). They are generally stabilized with one or more emulsifying agents.
Oral Suspension (solid in liquid dispersion): Liquid preparations for oral use containing one or more active ingredients suspended in a suitable vehicle. The ingredient is mixed with, but not completely dissolved into, a liquid. It needs to be shaken before administration to suspend the particles evenly.
Syrup: A viscous, concentrated aqueous solution of a sugar, usually sucrose, combined with other ingredients. The term often includes any oral dosage form (for example, an oral suspension) in a sweet and viscous vehicle.
Elixir: A clear, aqueous alcohol-containing (hydroalcoholic) liquid with dissolved ingredients. It may also contain sweeteners and flavoring substances. Elixirs contain between 5 and 40 percent alcohol.
Tinctures: An alcoholic or hydroalcoholic solution extract from vegetable materials or from animal/chemical substances. Most tinctures are prepared by percolation or by maceration. To qualify as an alcoholic tincture, the extract should have an ethanol percentage of at least 25 to 60 percent (or higher).
Oral Drops: Drops are liquid preparations for oral use that are intended to be administered in small volumes with the aid of a suitable measuring device. They may be solutions, suspensions or emulsions.
Buccal Sprays: Administration of ingredients via buccal mucosa (linings of cheek and area between upper and lower lips) to the systemic circulation, via a liquid spray mechanism. Normally used for small, water-soluble compounds; however, a potential route for compounds which are typically large, hydrophilic and unstable proteins, oligonucleotides and polysaccharides.
Advantages of liquids: 1) allow for easier dosage adjustments, 2) easier to swallow, particularly for children/elderly, 3) onset of action is faster than solid dosage forms, 4) faster rate of absorption, and 5) better bioavailability.
Disadvantages of liquids: 1) difficult to mask bad taste or odors, 2) may require a preservative system to prevent microorganism growth and improve stability, 3) potential for dosage inaccuracy, 4) bulky/inconvenient to travel with, 5) some oral liquids may be sensitive to oxygen or light and have been known to undergo degradation, 6) some ingredients are insoluble or may be chemically unsuitable in the presence of water, and 7) expensive to ship.
Robin Koon is executive vice president at Best Formulations, and has more than 35 years of pharmaceutical experience in clinical pharmacy, as a retail drug chain executive, in managed-care and in manufacturing.