Special Ingredients, Special Solutions

Special Ingredients, Special Solutions
by Steve Myers

Formulation challenges abound when handling unique ingredients and multiplenutrient combinations

The list of ingredients making the rounds in the natural products industry is quite extensive. And customers on all levels are demanding more accountability relative to safety, quality and efficacy of new formulations. This leads to a more complicated process for formulators of products containing numerous ingredients from the vast realm of compounds beyond the boundaries of vitamins and minerals.

First, there is an endless roster of ingredients. In the days of yore, formulations consisted of one or two basic nutrients, usually a vitamin, mineral or well-known herb. Fast forward to today, when formulators are faced with not only countless forms of vitamins and minerals, but also with numerous specialty compounds (both vegetarian and animal) and an ever-expanding cluster of herbs and botanicals. Christine Peggau, global market segment manager with Cognis Nutrition & Health, confirmed the simple life is no more. Read the ingredient statement on any nutrition bar or meal replacement beverage, she suggested. Often times a formula can have well over 20 different ingredients, each with its own functional characteristic.

From the latest antioxidant-rich fruit extract to the newest thermogenic herb, the hot or it ingredient of the month keeps formulators on their toes ... and in their reference libraries. We use all available reference sources to gather as much information as possible on an ingredient, and we create a dossier for our files, explained Don Brown, president of Boston Mountain Labs. Then we talk to our supplier and request they give us all the information they can can. We can spot and pass along any issues to the customer. As we run across new ingredients and data, well file them in our ingredient library.

However, the continuous influx of it ingredients poses even further problems beyond basic background knowledge. According to Emilio Gutierrez, vice president of East coast operations with BI Nutraceuticals, the industry has a long list of worthwhile products that do not necessarily have staying power on the shelf. Consumers try natural products and, for one reason or another, only a handful become lifetime users, he said. Many of the products in our industry are taken for longevity, well-being or preventive reasons, and it is difficult to keep consumers interested in the product when they dont feel an immediate therapeutic effect. What this means, he explained, is product life cycles are typically short and the industry is constantly trying to anticipate the next top selling new ingredient.

Gutierrez suggested the ingredients that seem to have the sustainability are those with the immediate feedback, which serves as a reaffirmation to continue taking the product. For this reason, we have enjoyed great success in the diet category with ingredients, such as green tea, that have metabolism-enhancing effects, he said. In the joint health category, consumers know the long term benefits of ingredients like chondroitin and glucosamine; in the muscle and fitness category, consumers look for various supplements such as such as L-arginine, creatine and R-lipoic acid.

In the popular weight management and sports nutrition categories, Eugene Ung, director of marketing for Best Formulations, reported regulatory and economic issues with otherwise popular ingredients have clouded the picture. Since ephedra was banned, there has been no clear winner in this category, he said, adding a large issue is the liability insurance that manufacturers must carry. No insurer wants to touch ephedra; even Citrus aurantium is extremely difficult (or very expensive) to get coverage for. In lieu of such beleaguered ingredients, Ung said green teamore specifically its phytochemical epigallocatechin gallate (ECGC)and hoodia are quite popular, and glucomannan (fiber) is making the rounds as well. Various formulators also report yerba maté is another fastgrowing ingredient in the diet and energy category.

In fact, formulators specializing in weight and sports products are getting requests to compile stimulant stacks similar to the once popular ephedra/caffeine/aspirin (ECA) stack. There are requests for combinations of stimulants that try to simulate the ECA stack like Citrus aurantium, guarana and white willow bark, along with green tea and hoodia to add to the label, Ung said. From a marketing perspective, compounding of stimulants appears to be what sells, as that is how you make your product stand out from others.

Increasingly found in the sports section, but also big in the antiaging market, chondroitin, glucosamine and MSM are still very strong staples in joint formulations, according to Ung and other formulators. In the anti-aging market, Ung said, Hormones have passed their curve, and anti-aging is focusing on condition specific products, with cholesterol, cardiovascular and joint products leading the way. He added coenzyme Q10s (CoQ10) strong research portfolio is attracting interest, and phytosterols are becoming increasingly popular for use in cholesterol-lowering formulations.

Brown echoed reports of a fast-growing market for phytosterols, saying beta-sitosterol and other sterols form one of the biggest product formulation segments. He added his company also does a good deal of business in saccharide reinductions and sees increasing interest in both grape seed extract (GSE) as an antioxidant and mushrooms for immune health. People are leery of mushrooms; but they feel better once you present them with the proper certifications and they do their homework on the mushroom, Brown said. It is a slower growth segment, but it is growing. In a broader view, he called immune health one of the hottest categories among natural and alternative medicine practitioners, who make up the bulk of his clientele. Seems like everyday well get a call from a practitioner wanting to discuss options for immune stimulation, he said, adding other hot areas include gastrointestinal health, diabetes and obesity.

In addition to trends of ingredients used in formulas, the type of finished product preferred and requested by clients is also undergoing transformation. Convenience is key, Peggau declared. Manufacturers continually strive to develop products that the consumer can pick up and enjoy on-the-run. She noted most of the delivery vehicles for nutritional ingredients such as sterols have historically been beverages and nutritional bars. We are also beginning to see products like chews, functional confectionaries (i.e. crosses between candy bars and nutritional bars) and single serve mix-ins for bottled waters, she added.

Among the formulation trends tracked by Neil Levin, a certified clinical nutritionist and nutrition education manager for NOW Foods, are amino acids, organic food products, personal care and non-GE (genetically engineered) products. NOW was the first large manufacturer to offer an Identity Preserved, non-GE vitamin E formula, he said, noting the company is trying to be as GE-free as possible. [Weve] switched to non-GE soy products whenever possible, and are seeking to avoid corn maltodextrin as an excipient or as a substrate for herbal extracts.

As with non-GE there is also a growing demand for vegetarian- and vegan-friendly formulations. Companies such Cognis are trying to go non-animal whenever possible, even to the point of revising existing formulas. Levin stressed this movement does not mean non-vegetarian products will disappear, but vegetarian ingredient options will prevail if they otherwise meet the specifications for the formula.

As for topical formulas, Levin pointed out some particular formulation requirements. Most people dont know that [developers] are required to expose a sample of each formula to a microbial contaminant to test whether the contaminant can grow on/in the formula, he explained. This is intended to provide an assurance of safety; however, this means that some form of preservative system is required in each product, making it difficult to be 100-percent natural or organic. Hammering home the notion of rising to challenging formulation issues, Levin said his laboratory experts developed a proprietary system to achieve the necessary stability, utilizing the most natural preservatives available and pioneering new strategies to minimize preservative use.

The concept of proprietary is not just for development processes and systems. We also see our customers differentiating themselves by offering unique patented or trademarked formulations, many of which are supported by clinical studies, Gutierrez said.

Rising to the Challenge

Considering the pool of unique functional characteristics in modern formulassuch as solubility, dosage, texture, flavor and potencyGutierrez advised of the formulation issues with certain popular ingredients. He noted green tea extract has poor flow; particles of both glucosamine and L-arginine are crystalline and not very compressible; creatine is hygroscopic (picks up moisture out of the air and becomes sticky); and R-lipoic acid is not very stable in its natural state. Each of these can be modified and made easier to use through different granulation processes such as roller compaction, high shear wet granulation and agglomeration, he advised.

Ung advised from an efficacy perspective, a formulator has to consider each ingredient and how best to put it in a dosage form that optimizes the absorption. For example, he noted CoQ10 is an excellent ingredient with a lot of research to back its benefits; but, CoQ10 comes primarily in a powder (crystalline) form that is not readily absorbed by the body. Therefore, the best way to formulate a product with CoQ10 is in a liquid soft gel form, he said. However, even in the soft gel form, there are challenges. Often the CoQ10 will re-crystallize in the soft gel, therefore defeating the purpose of putting it into the soft gel in the first place. Manufacturers who are highly experienced in working with CoQ10 in soft gels know how to process the material and include the proper carrier oils, etc. to ensure that the CoQ10 stays in solution and does not crystallize out.

Another challenge for formulators is phytosterols for cholesterol. Plant sterols are primarily in a liquid form that can be encapsulated in a soft gel. There are powder forms available for use in a capsule or tablet, but the concentration of phytosterols in the powder is much less than in the liquid, according to Ung. For example, if you want 500 mg of phytosterols, you can use the liquid form and have a fill of approximately 750 mg, which is a reasonable size soft gel, he said. If you want a capsule, then youd have to use the powder form, which depending on the concentration of the phytosterols in that powder, may require three to four capsules to obtain the same amount of phytosterols. Often, from a marketing perspective, the product may claim [itself] phytosterol powder, but the actual dosage of phytosterols may be much lower than the powder and, therefore, the effect would not be the same.

Levin said probiotics are also challenging, because moisture will activate them and shorten their shelf life. Refrigeration is one tool to extend that life, essential only because companies dont pack in glass and use appropriate moisture-binding package inserts, he reported. Such challenging ingredients are often best handled by trained experts. Levin noted a Harvard-trained Ph.D. and biologist working with his technical staff helped develop unique probiotic formulas that contain vigorous organisms that are cultured to assess their activity, and are in protective packaging that does not need refrigeration. He reiterated the notion that success demands formulators rise to challenges. In fact, he noted indole-3-carbinol (I3C), a phytochemical common in cruciferous vegetables, presents a particular challenge to formulation because of stability issues. This is one reason why its derivative, called DIM (diindolylmethane), is often sold instead, he said, noting his technical staffs meeting this stability challenge was the only way it was able to produce stabilized I3C, instead of DIM.

Phytochemicals are the hallmarks of herbs and botanicals, which present their own special issues to formulators. When dealing with herbal ingredients, the first and crucial step is proper identification. Any responsible formulator will do his due diligence, looking at the background and info on a particular herb if they are not 100-percent familiar with a particular herb and the problems it might pose in formulation, Brown said. As far as processing goes, you just need to make sure it will flow and do what you need it to do. He stressed the major concern with herbal formulas is what happens once it is in the consumers hands. No responsible formulator wants to put anything out that will come back on him, he reasoned. Therefore, it is important to use standardized extracts or have some assurance for consistency, as far as strength and potency.

Combining so many unique compounds in one formula can also heighten the possibility of interaction among ingredients and even other supplements or drugs a certain type of consumer might be taking. The more ingredients and areas of ingredients (vitamins, minerals, herbs, etc.) you involveespecially when you bring in herbs or desiccated organsyou have to be careful to not counteract within the formula or something your typical consumer might be taking (prescription), Brown advised, noting most practitioners and retailers want these formulas to offer consumers a part of an overall nutrition and health plan, or complete lifestyle change. Thus, it is important to be careful about dietary intake and how the ingredient form affects all these parameters; there are many considerations. He said as the number and type of ingredients grows, so does the formulators research and development requirement.

Acknowledging the importance of interactions and contraindications, Peggau reported that ingredients such as conjugated linoleic acid (CLA) and plant sterols are inert and rarely have interaction with other formula components. Therefore, developers typically can formulate using [such] ingredients without any additional processing steps or adverse effects on the finished product, she said.

Chemical interaction between herbal ingredients and common drugs, called contraindication, is a particular concern in herbal formulation. It gets quite complicated, depending on how uncommon the herb is, Brown reported. The more uncommon the herb, the more research required before formulation. He added if it is an herb that a formulator has dealt with a lot, one that is more commonplacelike ginkgo or echinaceait is less of an issue, as any contraindications are well known. However, other offerings, such as some of the Chinese herbs that are making the crossover recently, generate much more concern and require more research. Ive spent a lot of time researching lesser known Chinese herbs, he said. We get a lot of calls for these herbs, especially in formulas where they would intermingle with Western herbs.

One particular effect ingredients can have on a product is in taste, especially in the case of functional foods and beverages. If a food product does not taste good, it will not succeed, regardless of the associated health benefits, Peggau stated. This philosophy carries through to each individual ingredient in a formulation. Levin noted with the influx of more liquids, chewables and instant powdered mixes, the compatibility of the ingredients becomes more important. This includes pH, flavor, breakdown or solubility in water, mouthfeel, etc, said Levin. Adding sweeteners is another issue, as each has a different taste and mouthfeel.

Solubility can be an issue when formulating certain types of finished products, such as functional foods and even tablets and capsules. Many functional ingredients are lipid based, including sterols, CLA, lutein esters and beta-carotene. As we know oil and water dont mix, Peggau said. She added successful formulators utilize their process knowledge to make significant advancements in product development, which enables them to expand product lines to meet nearly every formulating challenge. Whether it requires water-dispersible powders or oil-soluble forms, highlyconcentrated pure forms or versions that have varying concentrations, we offer formulators ingredients to meet the most demanding production and formulating challenges.

The end goal of a formula is to get the most efficacious, high-quality ingredients into the consumer in the form, with maximum bioavailability and at the right dosage. Back when formulas typically contained one or two ingredients, this was more easily accomplished. But the complexity of modern formulations makes dosages a trickier affair. We constantly double-check on PDRs (Physicians Desk References) and standards to make sure we arent putting our clients in jeopardy, Brown said. We want to make sure we can make recommendations on dosages and ratios without getting them in trouble. In his case, his clients are mostly practitioners who already know the correct dosages and often pass along that info to the formulators. However, formulators serving non-practitioner clients must take it upon themselves to stay within safe and efficacious dose ranges.

The breadth and scope of current natural products formulation requires more than just keeping up-to-date on the popular ingredients and their dosages. With so many unique compounds, complex modern formulas require intricate modern technology. Years ago, the mindset was to keep the product as close to nature as possible and to avoid using any fillers with a name that sounded like a chemical, said Gutierrez, adding the typical solid dosage of choice was a two-piece gelatin capsule composed of mainly active ingredient. Some [current] formulations require the use of sophisticated ingredients (excipients) and manufacturing processes that are more commonly used with pharmaceuticals. So we find ourselves trying to develop raw materials that are either enteric coated or delayed release or quick dispersing like many of the OTC and prescription drugs available today.

Moreover, the modern processing equipment used by todays top manufacturers often dictates certain formulation parameters. Today, our customers are using high-speed encapsulators and tablet presses that require us to provide granulated products with superior flow, density and compressibility, Gutierrez noted.

As clients demand more accuracy, complexity and productivity from formulations, companies providing both formulation and contract manufacturing services have needed to spend significantly on expanded production and development of less chemically interactive ingredients.

Cognis just recently unveiled a $25 million state-of-the-art production facility in Illertissen, Germany, Peggau reported. In addition to increasing capacity for CLA and plant sterol esters, we have also improved our ability to produce premium quality ingredients that will not impact the great tasting products produced by manufacturers worldwide.

Modern formulation has definitely become more intricately demanding, with new and lesser-known ingredients, and the increased requests for more extensive ingredient inclusions in each formula. Also, the trend toward formulas targeting specific health problems or issues increases the care required to achieve the right dosage, while constantly being aware of interactions within or beyond the formula. While modernization of equipment and development of proprietary methods and forms offer formulators and their clients certain advantages, the most effective tool a formulator carries is the same tool formulators have relied on for centuries: knowledge. Constantly building your knowledge base is crucial, if you are going to be successful, Brown said. Clients who are trying to improve peoples health need to know they can count on you and trust you.