OR WAIT null SECS
Which formulation choices will support safety, efficacy, stability, and consumer acceptance.
New, innovative products and applications have been a major driver of growth of the cannabis industry. The range and number of new products is breathtaking and spans pharmaceuticals, food and dietary supplements, topical and personal care, and veterinary and pet food. It includes product formats ranging from prescription pharmaceutical formulations to capsules, chewable tablets, nutrition bars, gummies, drops, bottled water, beverages and sports drinks, creams, lotions, sprays, inhalation and vapor products, and pet snacks and treats.
In a significant milestone, in June 2018 the U.S. Food and Drug Administration (FDA) approved the drug Epidiolex (GW Pharmaceuticals), which is an oral solution of cannabidiol (CBD) for the treatment of seizures associated with two rare and severe forms of epilepsy. Epidiolex is the first FDA-approved drug that contains a purified drug substance derived from cannabis—in a strong pipeline of development and clinical testing.
Purified and concentrated cannabis extracts are powerful tools in product innovation. For medical applications, they allow the identification of the active ingredients, clinical testing for FDA approval and claims, and products that have defined potency and can be tested with established scientific methods for meeting specifications with consistency and stability. The same reasons increasingly apply to dietary supplements, beverages and sports drinks, and other applications. The use of purified and concentrated extracts also allows for the use of smaller amounts, which has significant benefits for taste, odor, color, or capsule and tablet size for oral supplements. The use of purified and concentrate extracts also facilitates accurate testing using smaller sample size.
Formulation is key to new innovative products and applications for the following reasons:
Let’s take a closer look at each reason.
Solubility in Water
Upon extraction and purification, important cannabinoids such as CBD and tetrahydrocannabinol (THC) come out as oils that are practically insoluble in water. For many products and applications such as beverages, medical formulations, sprays, topical formulations, and others, solubility in water is a must.
Increased Absorption and Bioavailability
Absorption of oils requires optimal function of the liver, pancreas, and the complete digestive tract. Absorption is also affected by the diet, age, and health conditions of the user. Clinically proven formulation technologies increase absorption and bioavailability especially in the large population segments with suboptimal absorption (1,2).
The stability and shelf-life of cannabinoids is affected by exposure to sunlight, air, heat, and other factors. When cannabinoids are added to water, foods, creams, and other products, their stability can be affected by exposure to oxidizing agents, acidic or alkali conditions, and reactive compounds. Customized formulations provide powerful tools for optimizing stability.
Taste, Odor, and Other Characteristics
Taste is of paramount importance in food, beverages, and other oral products. Odor is also important. Terpenes, which are abundant in cannabis plants, can have strong aromas that may be carried over into extracts, concentrates, and even purified cannabinoids. Formulation provides the opportunity for addressing the taste, odor, texture, and other characteristics for the specific products and applications.
For medical applications, formulation is required for accurate dosing of the desired product. With the expanding approval of cannabis products in the United States, Canada, and other countries, there is increasing focus on quality, testing and product specifications, potency, stability, and other product characteristics.
The top criteria to consider when choosing the right formation agents include safety, efficacy, positive or neutral effect on important properties, and support of label and customer preferences. Let’s explore each of those criteria in more detail.
The FDA’s GRAS (generally recognized as safe) designation is a top selection criterion. A long record of safe use on a daily basis, with significant safety margins across wide dose ranges supported by clinical evidence, provides additional confidence.
This criterion requires major homework, especially for the critical parameters of water solubility, stability, and increased absorption and bioavailability. While efficacy claims are abundant, few are supported by evidence. The gold standard is research and clinical evidence from leading universities and researchers, preferably supported by the National Institutes of Health (NIH) or similar quality funding organizations, and the results published in refereed scientific and medical journals.
Positive or Neutral Effect on Important Properties
This includes taste, odor, and color. For oral products, especially foods and beverages, taste and odor are of paramount importance.
Support of Label and Customer Preferences
Although there is no official definition of clean label, consumers increasingly show preference for minimally processed products with safe ingredients, preferably derived from natural sources. Additional consumer preferences include no sugar or salt added, free of gluten, dairy, and animal products, nuts and other sources of allergens, and nongenetically modified organisms (non-GMO).
The major cannabinoids, CBD and THC, are key components of innovative products. Increasingly, these cannabinoids are used in concentrated or purified form, especially for medical, dietary supplement and food and beverage applications, sprays, and topical products. Key objectives of formulation were discussed above and include:
A good number of solubilizing agents are available and include:
The choice of the right ingredients depends on many factors such as the properties of the active ingredient or the final form of the product. For example, cyclodextrins and solid monoglycerides have a key role in formulating tablets and other solid forms while others such as ethanol, polyethylene glycols, and glycerin support the formulation of liquids.
The increasing consumer awareness and strong preference for simple formulations using ingredients with proven records of safety and efficacy, and the major role of taste and odor, especially for oral products, have limited the practical choices dramatically. For example, polysorbates (such as Tween-80) which are common, strong solubilizers in the pharmaceutical, food and beverage, and cosmetic industries, can impact the taste. More importantly, an increasing consumer segment prefer products that do not contain polysorbates (4).
Vitamin E TPGS, a derivative of naturally sourced alpha-tocopherol is becoming the formulation ingredient of choice for cannabis products, especially purified or concentrated CBD and THC and other extracts. The reasons include:
Andreas M. Papas, PhD, is CEO and member of the Board of Directors of Antares Health Products, Inc., and an Adjunct Professor of Health Sciences of East Tennessee State University. A Fulbright Scholar, Dr. Papas is a graduate of the University of Illinois and author of The Vitamin E Factor paperback and editor of the scientific book Antioxidant Status, Diet, Nutrition and Health. Dr Papas also founded YASOO Health Inc., and led the company as President and Chair of the Board of Directors. He developed product concepts and managed successful commercialization including formulation, clinical evaluation supported by the National Institutes of Health and the Cystic Fibrosis Foundation, stability and safety testing, as well as pilot and commercial production and marketing. These disease specific nutritional products are considered the standard of nutritional care in cystic fibrosis, liver disease, and bariatric patients. Direct correspondence to: firstname.lastname@example.org
A.M. Papas, Cannabis Science and Technology 1(4), 56-59 (2018).