Delivery systems, from a science perspective, are the mechanisms that can either help or hinder a nutraceutical in­gredient's effectiveness. From a marketing standpoint, choosing a delivery system that improves over a previous one can serve as a point of differentiation for a product that was in dire need of a makeover (i.e., being able to claim "New & Improved" on the product label). There are several modes of delivery to choose from when you are talking about the oral delivery of nutraceuticals. These include bars (and other food systems), beverages, tablets, quick dissolving tablets, effervescent tablets, capsules, soft gels, lozenges, soft chews-even chocolate! But choosing a delivery system for a particular nutraceutical is not as easy as choosing one of the above. In fact, there are several issues to consider.

Delivery Issues

Nutraceutical delivery not only applies to the pill side of the market (dietary supplements) but also foods (and beverages), especially with an increasing number of companies achieving generally recognized as safe status (GRAS) for their ingredients. Each form of delivery poses a significant set of challenges. One of those challenges is consistency, according to Fred Wehling, president and CEO, Amerilab, New Hope, MN, developers of various effervescent technologies. "The challenge lies in the consistency of supply of ingredients, particularly with herbal extracts and natural ingredients," he said. "As producers of effervescent tablets and powders, which are designed to be dissolved in water and achieve a particular taste and appearance, the challenge is even greater. Variations in consistency of natural ingredients also can affect color, flavor, disintegration times and stability of the products."

Another issue companies have to contend with, said Charles Gay­­ser, technical director-Hu­man Health and Nutrition, Chr. Hansen, Milwaukee, WI, is cost. "There is a higher cost associated with unconventional de­livery systems as opposed to traditional delivery systems (immediate-release tablets and capsules)," he said, adding, "In addition, current manufacturing plant infrastructure is equipped for high throughput/conventional dosage forms." On top of that, he said, "Analytical development and testing costs are generally higher for non-traditional delivery systems and more time and development re­sources are required."

In terms of processing and formulation challenges, Pete Budde, technical service manager for the Human Health & Nutrition division at Chr. Hansen pointed out, "The ability to protect and deliver the desired component or active to the consumer, while maintaining the activity of the component through the processing, storage, handling and ultimately ingestion, is the largest challenge in providing a successful delivery system." Furthermore, he said, the ability for a delivery system to be considered "all-natural" is another key benefit in the nutraceuticals market.

Protecting the active is essential, especially for those involved in the probiotics arena. Joanna Wozniak, communications manager, Institut Rosell, Montreal, Canada, which supplies a host of probiotic strains and develops delivery technologies, said a lot of companies, in order to make a label claim, want to be able to guarantee a certain number of organisms by the time the product is consumed. So protecting these organisms and ensuring a certain amount of viable bacteria upon consumption is absolutely essential.

A delivery system is designed to deliver the most efficacious amount of active over a time period in a format that is consumer-friendly, said Eric Smith, vice president of marketing, Penwest Pharmaceuticals, Patterson, NY, which is an oral drug delivery company that develops technologies such as Redi­Run™, ProSolv ® and TIMERx ®. The challenge is fostering compliance and orchestrating an appropriate release profile for the active. Other issues, ac­cording to Mr. Smith, include standardization and education. "I firmly believe that if the nutraceuticals industry is going to be successful in the future, they have to educate consumers to make sure they understand what they are taking and how much," he said.

Roger Shahani, director-North A­merica, Pan Pharmaceuticals, Sydney, Australia, which produces several effervescent technologies, said some delivery systems lack visibility in the marketplace due to compliance issues. "There are many delivery systems that are used quite widely in overseas markets, which still have not really penetrated the U.S. because it takes a lot of effort on the part of marketers to get people to try and use these new systems," he said. "Effervescent delivery has yet to catch on because it takes 90 seconds for effervescent tablets to dissolve in a glass of warm rather than cold water. These compliance issues can be a deterrent." The good news, according to Mr. Shahani, is that this is all changing. "In terms of effervescent de­livery, I am noticing quite dramatic uptake, especially in multi-level marketing channels, which are always looking for unique and innovative products."

Dr. Ram Chaudhari, senior executive vice president of re­search and development for premix supplier Fortitech, Schenecdtady, NY, discussed the issue of efficacy. "One should not think that a nutraceutical delivered in powdered form is less efficacious than a tablet or capsule. In food form it be­comes easier to mask the taste of certain ingredients because they provide macronutrients like proteins, carbohydrates and some fat," he said. "There are tradeoffs to which delivery system you choose. Tablets and capsules are great and very convenient but you have to have some substrate (proteins, fats, carbohydrates) in order to make use of some of the ingredients or they will not have as good an impact."

If companies are considering food as delivery for nutraceuticals it is no secret that taste will always be a concern. "One of the biggest challenges for manufacturers of health foods is to make their product taste good," said Carl Pacifico, new ventures development leader, Balchem Encapsulates, Slate Hill, NY. "Formulators who want to use amino acids, B vitamins or botanicals can count on these nutrients imparting an un­pleasant taste. Only a small segment of consumers will accept a finished product that tastes bad; and no amount of chocolate, peanut butter or sugar can improve the overall taste to capture the next segment of consumers." What will help in this situation, is encapsulation. Mr. Pacifico explained, "Encapsulation can be used to meet the challenge of taste masking. In this case, the capsule wall must not be breached even during chewing. For example, guarana, a natural form of caffeine with a very bitter aftertaste, can easily be included in confections without affecting the taste if the encapsulated form is used."

Making a label claim is also an issue companies must consider, said Ellen Schutt, marketing director of OxyPhyte® supplier RFI Ingredients, Blauvelt, NY. "If you want to be able to say something specific about your product (i.e., a health claim or structure/function claim) then you need to choose a delivery system that allows you to do that," she said.

How do You Take Your Nutraceuticals?

Consumers are becoming increasingly hard to please as shown by the number of delivery systems that have e­volved over the last few years, not only for nutraceuticals but for drugs and foods alike. For example, some consumers prefer to get their calcium in a beverage or soft chew because they don't consider calcium pills consumer-friendly. Others prefer to take calcium in pill form because it lessens the burden of trying to get their calcium from multiple sources throughout the day. Consumers also have a tendency to choose a delivery format based on a health condition they are looking to prevent. According to the Health & Wellness Trends Report 2003 from the Natural Marketing Institute (NMI), Harleysville, PA, the latter certainly seems to be the case. NMI's Health & Wellness Trends Report tracked consumers' preference of supplements versus foods, according to health condition. The highest preference for use of supplements over foods/beverages for prevention of health issues appeared to relate to aging consumers, especially in the areas of arthritis, memory and menopause. On the other side of the spectrum, consumers favored food/beverages when it came to the prevention of obesity/overweight, diabetes and high cholesterol (see Table 1).

In terms of the supplement category alone, The Health & Wellness Trends Report also tracked consumers' preference of supplement format. In the survey, which is balanced to the U.S. general population, a majority of respondents said they use tablets, capsules and soft gels most of the time. Bringing up the rear was fizzing (effervescent) tablets (in water) at 4% of re­spondents using this format for supplement delivery (see Figure 1).

Whatever the delivery format, there are several exciting things happening in the area of nutraceutical delivery. And although not exceedingly popular at the moment, Mr. Wehling of Amerilab said effervescent products have a lot of po­tential. "As one of only a handful of effervescent manufacturers, we are well aware of the increased interest in effervescent delivery systems across the nutritional products industry. I think this is largely because of the large doses of active components, which can be delivered at one time with this type of product," he said, adding, "An effervescent system also has the unique ability to flavor a product to taste good where a normal liquid formula may not." In addition, he said, there is a large body of research on effervescent pro­ducts, which support claims of much greater absorption over a much shorter period of time.

Other up and coming dosage forms offering companies product differentiation include the fast dissolving tablet and concentrated liquid, according to Mr. Wehling. "With a fast dissolving tablet, a consumer simply places the tablet in their mouth and it dissolves in 30 to 45 seconds without the need to drink water or a beverage to wash it down," he said, adding, "Another convenient form of dosing that is beginning to make its way into the market is the concentrated liquid. With this form of delivery, a few drops of concentrated liquid can be taken to obtain a dose of the active ingredient. The big­gest draw­back to this system and the fast dissolving tablet is still taste, but as companies are continuing to try to diversify and gain market share, they are viable options for marketing something new to the consumer."

Tamara Smith, department head-Marketing, Shionogi Qualicaps, Whitsett, NC, said non-gelatin alternatives is a hot trend right now because certain portions of the population demand them. "Vegetarian capsules are of interest for two reasons; the first being that it is a non-gelatin alternative, and second, the capsules are more compliant for vegetarian lifestyles and some religions," she said. "The most popular non-gelatin alternative is made from hydroxypropyl methylcellulose (HPMC)."

According to Beverly Emerson, marketing director, Banner Pharmacaps, High Point, NC, developer of Soflet® gelcaps and other proprietary delivery systems, there is a trend toward pharmaceutical-oriented delivery. "We are beginning to see a trend toward pharmaceutical delivery systems that require a much higher level of research and development to support," she offered. An example of this includes Banner's recent development of an enteric soft gel. "The enteric system is built into the soft gel, not a coating that is added on top, so the finished product is far more stable, as well as clear in color," Ms Emerson explained. "This is revolutionary in both the pharmaceutical and the nutritional industries. Within the nutritional industry it will have strong application in fish oil, garlic oil, probiotics, peppermint oil and other compounds that need to be released in the intestine rather than the stomach."

Doug Usifer, business director-Food Emulsions and Targeted Delivery, National Starch & Chemical Corporation, Bridgewater, NJ, feels the trends in delivery center around protection and performance. "The trends for systems are moving toward meeting market needs for higher performance in both protection and delivery," he said, adding. "Better protection of the active against oxidation, humidity and temperature would be examples. Higher delivery performance would mean getting the active to the right place, in the right amount, at the right time, at the lowest total cost."

Sam Wright, president and CEO, The Wright Group, Crowley, LA, which supplies a range of premixes, identified some trends he is noticing. "Among the most prominent trends is a return to traditional vitamin and mineral-based fortification blends that include functional ingredients that have been thoroughly researched and provide a proven health benefit," he said. "Customers are also requesting cus­tom formulations composed of ingredient combinations that address a particular wellness benefit (i.e., ocular, joint and cardiovascular health). Nutra­ceutical microencapsulation is also proving to be a popular item a­mongst our customers."

Aside from micro­encapsulation and enteric coating, which are still high on the request list at Institut Rosell, Ms. Wozniak said there is also increased demand for probiotics in stick format (called this because it is 2-3 inches long and about half an inch wide). "Stick format is designed so that you can tear off the end and pour the contents into a liquid or over a solid (i.e., juice, yogurt or mashed potatoes). The stick can also be poured into the mouth directly," she said. "We are seeing a lot of requests for this format in a number of flavors, especially for children."

Adding to this was Thomas Tompkins, biochemistry and microbiology research director for Institut Rosell "I think the stick format has been very well understood in Asian countries and in Europe, but in North America it is just starting to hit the radar screen in terms of consumer awareness," he said. "With a stick format you can deliver a much larger amount of an ingredient, with the option of adding in other components such as fibers, flavorings or minerals."

Convenience has also become a major trend, according to Julie Wagner, director of research and development-Dry and Specialty Products, Century Foods, Sparta, WI. "Our whole society has become more convenience oriented and as a result, this will be a major driver in choosing a delivery system for products," she said. She discussed the convenience issue from a sports nutrition perspective. "What we are familiar with is the trend in protein. As products continue to go up in protein, it becomes harder to get it into solution," she said. "To solve this problem we agglomerated the protein, or instantized it, so that it would go into solution more readily. It seems a more ready-to-drink version has become the next generation of products."

Discussing the trend toward timed-re­lease products was Dr. Richard Salz­stein, pharmaceutical sales manager, Aqualon division of Hercules, Inc., Wilmington, DE, suppliers of Benecel® and Klucel Nutra™. "There has been a move away from immediate release to more modified or sustained release products," he said. According to Dr. Salzstein this is because consumers are looking for the physiological effects that will eventually follow. As an example, he said, "A large dose of vitamin C in the morning is not necessarily as good as vitamin C released over the course of several hours. This is also true for niacin as well as glucosamine and chondroitin."

Choosing a Delivery System that Fits: What Companies should Know

Companies must realize that there is no "one size fits all" approach when it comes to nutraceutical delivery. As an obvious example, some nutraceuticals do not tablet as well as others. Furthermore, some ingredients are more sensitive in terms of processing conditions and, in addition, may require delivery to certain sites in the body (e.g., probiotics). That said, choosing a delivery system that suits a particular ingredient is paramount.

Banner Pharmacaps' Ms. Emerson offered her perspective on how to evaluate a delivery system. "There are two key issues with determining which delivery system is appropriate for nutraceuticals. The first pertains to maximizing effectiveness through the delivery system. For example, while tablets are generally a first choice for dietary supplements, there are a number of instances when this may not be desirable," she explained, adding, "In other cases, ingredients will be rendered ineffective when exposed to gastric fluids, and some compounds can be very irritating to the stomach. In these instances the solution may be a delivery system with enteric properties, whereby the compound will not be released until it reaches the intestine."

Another reason companies may choose one delivery form over another has to do with maximizing palatability. Ms. Emerson offered, "When the decision is made to deliver nutrients orally then maximizing palatability becomes an issue. Furthermore, if a pill is too large, too hard to swallow or tastes bad, consumers will simply stop taking the product."

Marie Garnich, senior director of new product commercialization at Penwest said companies should do some re­search to find out what system will best suit the active they want to deliver. "We know that there are limited ways to deliver some actives because they don't tablet well or the active is an oil like vitamin E. The delivery system should be chosen first, depending on the active-that's critical," she commented. "Companies should also take into consideration the population they are targeting and decide how they would really like them to take the product (e.g, one tablet over time or twice a day)."

Institut Rosell's Ms. Wozniak agreed on the latter. "You would not, for the most part, deliver nutraceuticals in the same format for an adult as you would a child. With a child you are probably going to want something in a sachet format or chewable tablet."

Similarly, Mr. Tompkins added, "Companies also need to know who is giving out their product, whether it will be given out by dietitians or in a hospital setting with a nurse or at home. This is essential to consider because a sachet might be ideal for the home but if a nurse had to dispense 40 sachets each meal time that might be a little time intensive, and in that case you would probably want a capsule or a chewable tablet depending on what the application is and who it is going to."

Challenging Ingredients

In determining what ingredients are most difficult to deal with in terms of delivery systems, Century Foods' Ms. Wagner said all ingredients pose their own distinct difficulties. "Each ingredient has its own benefits and limitations not just on its own but in combination with other ingredients," she said.

Chr. Hansen's Mr. Gayser pointed out several ingredients including SAM-e because it is chemically unstable, hydro­philic and acid labile; amino acids be­cause they are hydrophilic and require high doses; enzymes because they are hydrophilic and unstable in the presence of moisture; fiber because of the high dose requirements and probiotics because they are unstable in the presence of heat and moisture.

Fortitech's Dr. Chaudhari said Co­Q10, omega 3's, choline, L-carnitine and glucosamine and some of the botanicals may be fantastic ingredients from a nutritional perspective but they can present some unique challenges and require special handling during manufacturing.

Mr. Salzstein discussed high dose products, low soluble actives and ingredient variations. "If you are trying to deliver 1000 mg of an active ingredient or a combination of ingredients, you need to be able to tablet that or put it into a dosage form," he said. "The difficulty is determining how large you go with the tablet or capsule or deciding if it will have to be taken twice a day." Another issue with ingredients, Mr. Salzstein said, is having a low soluble active. "If you have an active that has low solubility, once it gets into the gut and is released from the tablet or capsule, then the goal is to get that into the gut fluid-which is typically water-based-and then get it to cross into the gut absorption system. That is a general challenge, however, there are systems out there that try and encourage that solubility," he said. Lastly, he suggested, "A delivery system should be robust enough that it can handle variable physical properties and won't require that every batch be reformulated because there are slight variations. A good delivery system should be able to weather various manufacturing and sourcing conditions."NW