The very word “unstable” is one that engenders fear. An unstable person is capable of acting violently, an unstable economy leads to recession or depression, an unstable structure can collapse, an unstable weather pattern can lead to natural destruction—and unstable ingredients can lead to emergency room visits and product recalls.

Stability, it would then be surmised, is a ubiquitous common goal of achievement.

In the vast world of natural ingredients for human health, stabilizing volatile compounds of natural origin is paramount for safety and efficacy through manufacture, packaging, transport, and retail and home shelf life.

When determining the shelf life of a product, Ed Wyszumiala, general manager for Michigan-based NSF International Dietary Supplement Programs, pointed out even before setting up the necessary stability studies, the longest potential target for a shelf life date of a finished product will be the date of the least stable ingredient.

That knowledge, he said, is essential in determining the best starting point for the setting of a product’s expiration date. This is also important when formulating products, as the ingredients overage for a formulation may need to be determined in order to meet a prolonged expiration date for a product.

Further, he said, “If expiration dates or voluntary claims such as ‘best by’ or ‘use before’ appear on a nutritional supplement label, FDA officials expect supporting stability test data to be available and they will ask for it during GMP inspections. Dietary supplement companies can be proactive and use NSF’s Stability Testing Guidelines to ensure their expiration dates are backed by sound science.” 

The guideline requires that nutritional supplement companies identify the physical, chemical and microbiological characteristics under long-term storage. It specifies that companies understand the impact that manufacturing, packaging, labeling, distribution and holding/warehouse processes may have on a product’s stability. The guideline also proposes that stability testing be conducted in the same container used for marketing the nutritional supplement product.

Overall, Wyszumiala said there are many challenges right now surrounding the stability of ingredients and how unstable ingredients affect the stability of finished products. There are numerous factors that need to be considered, such as: overages in manufacturing, degradation by-products and rancidity. Factors involved in stability testing include dietary ingredient strength, chemical fingerprints, microbial growth, preservative content, moisture content, pH, viscosity and oxidation, among other parameters, such as the product’s container-closure system.

Problematic Ingredients 

Some ingredients are more persnickety than others. Probiotics head the list because, unlike other supplemental ingredients, these must be kept alive, awake and ready to colonize when they find their new neighborhoods in users’ intestines.

Michael Shahani, COO of Nebraska Cultures, Inc. in California, said that the bifidobacteria strains are the most difficult probiotic strains to stabilize and are very susceptible to heat and moisture. Probiotic bacteria (as with most that exist) only live under a narrow range of conditions. “So keeping them alive for a long time is difficult, but that is what must be done commercially,” he said. “The bacteria want to keep growing, but if there is no food source, they will eventually die. Freeze-drying them makes them ‘dormant,’ but they won’t live forever in that condition.” 

Probiotics, agreed Kenn Israel, vice president of marketing with Californiabased Robinson Pharma Inc., are indisputably the most challenging ingredients to work with, as they need to be alive, viable and testable in the completed dosage form. The manufacturing environment and technique, especially soft gel production, could better be described as a way of destroying these organisms, so a method for preserving and delivering these actives to the body is necessitated. “The entire process needs to be considered when building a delivery system for probiotics. This is further complicated by the fact that accelerated stability techniques with their increased heat and moisture are specifically challenging to this class of active ingredients,” he explained, offering a comparison. “While reduced-form antioxidants (Kaneka’s QH, for example) and especially fragile lipids (free fatty acids in highly concentrated form) can be challenging, the complexities of probiotics are much tougher.” 

Fish oils, too, pose quite the challenge to ensure stability through consumption. “They are definitely the most finicky to stabilize,” conceded Andrew Aussie, executive vice president and COO of Coromega in California, explaining that fish oils are unstable and very sensitive to oxygen and light due to the large number of polyunsaturated fatty acids they contain. “Unsaturated fatty acids have double bonds between their carbon atoms. Reaction of fish oil with oxygen results in the cleavage of these double bonds and the release of volatile components that gives the oil a rancid/fishy smell and taste. Conversely, saturated fats have no double bonds, so they oxidize more slowly.” 

Further, Dr.Dorit Rozner, research and development manager for New Jerseybased Lycored, Ltd., noted that carotenoids also seem to dislike oxygen and are quite sensitive to degradation once exposed to air.

Stability Solutions 

And yet, these companies have found ways to preserve the vitality of these ingredients through the arduous journey of extraction through consumption. Nebraska Cultures, said Shahani, does not claim to have the “magic bullet” that will stabilize all probiotics at room temperature indefinitely, but it has developed a proprietary stabilizer that is added to all its strains. Dr. Khem Shahani, company founder and a professor at the University of Nebraska for more than 40 years, developed a proprietary blend of natural vitamins, antioxidants and amino acids that serves to help stabilize the probiotic bacteria in a freeze-dried state.

Shahani maintains that still, all the probiotic manufacturers, including Nebraska Cultures, recommend refrigerating probiotic bacteria to ensure longterm stability. “There is still no substitution for that,” he stated, noting that spore-forming strains such as ProDURA Bacillus coagulans are very stable at ambient temperature for years, and the use of these strains is increasing, along with research supporting their use.

When Robinson Pharma developed its soft gel delivery system for the Unique IS-2 Bacillus coagulens strain, every aspect of the production and formulation process was considered and in many cases modified, according to Israel. Careful consideration was given to carrier oils, mixing methods, holding and production temperatures, interaction between fill and shell materials. Many trial batches were produced and analytical methods needed to be fine-tuned and updated then transferred to additional labs. Ingredient specifications and characteristics required modification. “This project took more than a year, required hundreds of man hours and many thousands of dollars in investment in trials and analytical testing,” he said. “The organizational commitment to this type of project is very large as you don’t know if it will succeed when you start.” 

Fish oil, by its nature, is difficult to stabilize because of its susceptibility to degradation from oxygen and light, Aussie pointed out. Coromega was able to achieve stability of fish oil though emulsification, which he said also results in a higher absorption benefit and a great taste experience. “It’s especially important to have a stable formula to maintain a positive taste experience.”

Coromega uses an emulsification process to create its product, and controls stability with a very delicate and proprietary balance of stabilizing ingredients. The company also manages a low water activity level, uses a light-barrier package and nitrogen-flushes its product during packaging to assist long-term stability and protection from degrading oxygen and light. “It’s important for us to ensure our fish oil offers the nutrition, taste and freshness stay good for an extensive period of time— one to three years,” said Aussie. “Long shelf life provides retailers peace of mind in bringing the product into inventory and confidence in having the time to sell the product.” 

In the case of carotenoids in Lycored’s starch beadlets, the company overcame the stability challenges by using excipients that are oxygen-resistant, and combined with the right antioxidants. The result: Lycored has created stable actives, explained Rozner.

“Another important parameter is the particle size,” he added. “By using beadlets and not thin powders, we create a small surface area so there is less exposure to air and the result is a freeflowing powder that can be used in a variety of applications, such as traditional and effervescent tablets, powdered beverages and hard shell capsules. Further, this technology is particularly helpful when required for food applications such as baking.” 

Rozner’s statement reflects the continued rapid growth of the natural health industry, which is blending supplements with foods and beverages, expanding consumer choices beyond conventional capsules and tablets. This makes the stability issue even more important a conversation.

“The growth and future of our industry depends on us—(as individual companies and as an industry)—being able to create innovative solutions that deliver clinically proven ingredients that provide real and experiential benefit to the consumer,” concluded Israel. “The products of tomorrow need to be effective and stability is a basic requirement for efficacy. Otherwise we are selling broken promises, and that never goes well.”