By Mike Montemarano, Associate Editor03.01.23
As dietary supplement manufacturers branch out and experiment with novel dosage forms, breakthrough delivery solutions are needed to ensure that products still provide what’s promised on the label. In the absence of solutions that improve solubility, bioavailability, and metabolism, many ingredients are less compatible with gummies, chewables, powders, shots, functional foods, and more.
Two key forces are driving innovation in the dietary supplement industry, according to Charlie Ross, senior vice president, Americas, for human health and nutrition at Aker BioMarine. “First is the demand for new and novel products, and secondly is the importance of bioavailability and absorption of ingredients. Three in four supplement takers will pay 10% more for supplements that are better absorbed.”
Pill fatigue, previously common in children and the elderly, now applies to the general population, noted Maggie McNamara, marketing director at Gencor. “It really isn’t surprising. About 66% of U.S. adults take prescription drugs, more than 26% of UK adults take prescription medications, about 35% of Australians take prescription medicine every day, and in Canada, about 65% of people aged 40-79 take one or more prescription drugs.”
However, if formulation flexibility is the priority, don’t count out breakthroughs in capsules, said Emily Navarro, global marketing manager of Lonza Capsules and Health Ingredients. “Capsules offer a lot of flexibility as a dosage form, making product innovation easily accessible for brands while delivering on non-negotiable consumer values like convenience, swallowability, and efficacy.”
“Many consumers are adopting liquid-RTD (ready-to-drink) options in children’s vitamins, hydration and electrolyte products, and even in multivitamins,” said Haleigh Resetar, corporate communications specialist at SPINS. “More and more shoppers want vitamins that can be integrated into part of their diet, apart from taking them as pills. Instead, they want to add them to beverages such as their protein drinks or morning smoothies to streamline their routine.”
In 2022, the dietary supplement market was dominated by liquid RTD formats ($3.4 billion, +5.6%), gummies ($2.7 billion, -0.4%), powders ($2.4 billion, +14.5%), tablets ($1.8 billion, -6.3%), softgels ($1.5 billion, -5.4%), and capsules ($1.4 billion, -5.3%).
“Gummy forms will continue to keep a large market share in the VMS (Vitamin, Mineral, and Supplement) space as their popularity among all demographics is substantial, but we can expect powder and liquid-RTD options to keep staking out their claim to the overall share,” Resetar said.
Powdered blends and RTD formats are especially popular for condition-specific products, said Eric Meppem, co-founder and commercial director of Pharmako Biotechnologies Pty Ltd. “This has been due to an increase in collagen-based powdered products in beauty, sports, and joint segments, and more recently due to new technologies allowing for novel formats.”
“Gummies are not going anywhere soon but I do expect that alternative, more creative delivery formats will take away a bit of that market share,” McNamara added. “For example, jelly beans and soft chews are gaining popularity, especially (among) Gen Z and Millennials.”
Absorption remains the number-one factor holding back innovation when it comes to novel delivery platforms, said Ross. “We are seeing consumers drop supplements because they are not seeing and feeling the benefits. In order to find success with innovation, we need to check off all the boxes and bioavailability/absorption is a big one.”
Many nutritional ingredients can’t be added to gummies and other platforms at the same clinically-relevant dose as traditional formats like tablets, capsules, or softgels. Actives may also be less absorbed into the bloodstream.
Controlling the release and timing of an ingredient’s activity is another key challenge. This is especially relevant in supplements that contain two or more ingredients that may interfere with one another. Sustained-release technologies can also overcome challenges related to the time frame of an ingredient’s activity, such as with caffeine or melatonin.
A study published on a sustained-release caffeine ingredient marketed as CaffXtend by Nutriventia, for instance, found that compared to instant-release caffeine, participants who had caffeine gradually enter their system over an extended time period had a better mood and fewer untoward effects typical of caffeine use (The Journal of Dietary Supplements, January 2023).
Top vitamin and supplement brand NatureMade recently added several sleep products to its Wellblends line, featuring a time-release melatonin to address specific night-time complaints such as wanting to sleep longer or being able to fall back asleep in the middle of the night.
While new capabilities are emerging, not all technology platforms are subject to the same quality controls and testing rigor, Meppem cautioned. Further, it’s important to verify that throughout manufacture, sensitive and volatile ingredients themselves were handled according to current Good Manufacturing Practices (cGMPs).
“Quality of manufacture is a considerable challenge, and not readily recognized,” he said. “Manufacturing delivery systems and verifying them with proper quality controls, pharmacokinetic, and clinical validation is not necessarily common. Product stability challenges can be an issue with complex delivery systems.”
Liposomes are tiny particles that can encapsulate both hydrophilic and hydrophobic nutrient particles at the microscopic level, and their use has been recognized for improving bioavailability of nutrients.
“There is currently a great deal of interest in liposomes,” said Meppem. “They are more than just an interest or a trend now. However, there is a variety of quality in the market, and not all are properly verified as ‘liposomes,’ but are just labeled that. Liposomes can also assist in overcoming degradation or elimination of an active by the human body’s own immune system.”
Self-emulsifying systems can make certain nutrients compatible in areas they never were before, Meppem added, such as by reducing a dosage needed to achieve clinical efficacy. For instance, Gencor’s AquaCelle technology, a self-micro-emulsifying drug delivery system, was developed to reduce pill sizes for oily ingredients such as fish oil, algal oil, or krill oil.
The company’s compressed powdered oils (CPO) technology can also incorporate these ingredients as powders into two-piece hard capsules mixed with other powders.
Meanwhile, Pharmako offers LipiSperse, which can make lipophilic plant extracts suitable for a range of formats. “LipiSperse technology was originally developed to assist a Spanish customer in including lipophilic curcumin into a ready-to-mix sports nutrition powder. Regular curcumin with magnesium and collagen just forms a sticky orange mess,” Meppem said.
“LipiSperse allows lipophilic powders such as curcumin, resveratrol, silymarin, quercetin, and more to disperse in water. LipiSperse-powered ingredients such as HydroCurc (curcumin), VeriSperse (resveratrol), or Levagen (palmitoylethanolamide) can be used in formats such as effervescent tablets and powders, direct-to-mouth sachets, gels, and gummies, which was previously impossible.”
According to CEO Suresh Kolla, it took six years to hone flavor masking, ensure ingredients would be intact and viable, and confirm the format could contain 250 mg of any active ingredient in one melt.
“I was truly motivated by several factors,” said Kolla. “The quality of ingredients and research on dietary supplement ingredients continued to grow, with news of ingredient launches and new studies proliferating. In tandem, I have several individuals in my life who have difficulty swallowing pills effectively, which is common. Gummies are the go-to for the pill-averse population, but they also tend to carry some issues of their own—undesirable sugars, and their very texture can interfere with dentition in some individuals. My team and I also researched bioavailability, and found that buccal absorption provided a quicker delivery of the nutritional compounds within the melt.”
Phospholipids, which encapsulate the omega-3 fatty acids in krill, have surfaced as a platform for delivery of other ingredients. Aker BioMarine has developed a phospholipid-based technology platform called PL+, which utilizes krill phospholipids as carriers for other ingredients.
“While there are some solutions in the market that help solve these issues, many are synthetically made, and include a long list of unknown ingredients and don’t offer benefits beyond absorption,” said Ross. “PL+ technology not only improves the absorption of certain ingredients, it also supports healthy cells which deliver health benefits throughout the body. With PL+, we are creating supplements with improved absorption, reduced formulation costs, and enhanced product quality.”
“In the next few years, we expect the advanced capabilities of liquid-filled capsules to have a significant impact on nutraceutical product development,” Navarro said. “Leveraging the versatile polymer options for capsules, as well as technologies like Lonza’s capsule-in-capsule delivery system will also enable advanced combinations and formulations, whatever the ingredient format.”
Navarro noted Lonza’s focus on the sensory appeal of capsules can help to meet heightened consumer expectations. “For some plant-based or botanical ingredients, masking unpleasant tastes and odors can help avoid an off-putting experience for consumers,” she said. “Consumer experience is also key and a product’s dosage form can help a brand stand out on shelves. New flavor and aroma coating technologies can create a favorable sensory experience, and vibrant food-colored capsules offer consumers that ‘Instagrammable’ moment.”
Capsules often offer the greatest control over factors such as moisture, light, and oxygen sensitivity, bioavailability, and taste and odor masking.
“For stability, this primarily comes down to the type of polymer being used. For example, hydroxypropyl methylcellulose (HPMC) capsules deliver greater opacity to prevent UV light penetration, whereas pullulan capsules, made from a compound resulting from a natural tapioca fermentation process, offer low oxygen permeability for oxygen-
sensitive ingredients.”
Tailoring capsule type with the survival and performance of a specific ingredient in mind is another emerging trend, said Navarro. Lonza offers Capsugel DRcaps specifically to protect probiotics as they are exposed to gastric acid.
Lonza also offers a specially-designed capsule with a micro-spray sealing technology in order to prevent leaks and clumps.
“Smaller batch sizes or runs are more cost-effective, not necessarily for the contract manufacturer, but for some brands,” said Meppem, “so using Pharmako’s CPO technology to move oils into powders allows smaller batches of two-piece hard capsules rather than softgel capsules. These formats also more easily cater to vegan or vegetarian consumers. AquaCelle has published human pharmacokinetic data validating it increases the absorption of key actives such as omega-3s, coenzyme-Q10, and lutein. Decreasing a dose by up to six times is true cost-saving, and a much better use of resources.”
According to Navarro, capsules are a cost-saver because they eliminate the need to use excipients that would otherwise be needed for machinability or powder flow. Smaller batches and pilot batches at the front end of product development are another means of reducing waste and lowering cost.
“Capsule design, as well as manufacturing and equipment technology can also help cut back on overfilling, which conserves ingredient resources and reduces costs,” she said, adding that trimmings from some gelatin two-piece capsule manufacturing processes “can be reused and re-melted to rejoin the production cycle, diverting a potential waste stream and again saving valuable resources.”
In addition, equipment that allows for small batch runs during product development allows brand owners or contract manufacturers to perform pilot batch programs and streamline their production processes, while reducing capsule failure rates before full production, Navarro said.
Two key forces are driving innovation in the dietary supplement industry, according to Charlie Ross, senior vice president, Americas, for human health and nutrition at Aker BioMarine. “First is the demand for new and novel products, and secondly is the importance of bioavailability and absorption of ingredients. Three in four supplement takers will pay 10% more for supplements that are better absorbed.”
Pill fatigue, previously common in children and the elderly, now applies to the general population, noted Maggie McNamara, marketing director at Gencor. “It really isn’t surprising. About 66% of U.S. adults take prescription drugs, more than 26% of UK adults take prescription medications, about 35% of Australians take prescription medicine every day, and in Canada, about 65% of people aged 40-79 take one or more prescription drugs.”
However, if formulation flexibility is the priority, don’t count out breakthroughs in capsules, said Emily Navarro, global marketing manager of Lonza Capsules and Health Ingredients. “Capsules offer a lot of flexibility as a dosage form, making product innovation easily accessible for brands while delivering on non-negotiable consumer values like convenience, swallowability, and efficacy.”
'Gummy forms will continue to keep a large market share in the VMS (Vitamin, Mineral, and Supplement) space as their popularity among all demographics is substantial, but we can expect powder and liquid-RTD options to keep staking out their claim to the overall share.'
—Haleigh Resetar, SPINS
Market Share
Gummy supplement sales were essentially flat in 2022 (down 0.4% for the past year ending Jan. 1, 2023), according to data from SPINS. This was a notable slowdown compared to the 23% growth for the 52 weeks ending Dec. 26, 2021.“Many consumers are adopting liquid-RTD (ready-to-drink) options in children’s vitamins, hydration and electrolyte products, and even in multivitamins,” said Haleigh Resetar, corporate communications specialist at SPINS. “More and more shoppers want vitamins that can be integrated into part of their diet, apart from taking them as pills. Instead, they want to add them to beverages such as their protein drinks or morning smoothies to streamline their routine.”
In 2022, the dietary supplement market was dominated by liquid RTD formats ($3.4 billion, +5.6%), gummies ($2.7 billion, -0.4%), powders ($2.4 billion, +14.5%), tablets ($1.8 billion, -6.3%), softgels ($1.5 billion, -5.4%), and capsules ($1.4 billion, -5.3%).
“Gummy forms will continue to keep a large market share in the VMS (Vitamin, Mineral, and Supplement) space as their popularity among all demographics is substantial, but we can expect powder and liquid-RTD options to keep staking out their claim to the overall share,” Resetar said.
Powdered blends and RTD formats are especially popular for condition-specific products, said Eric Meppem, co-founder and commercial director of Pharmako Biotechnologies Pty Ltd. “This has been due to an increase in collagen-based powdered products in beauty, sports, and joint segments, and more recently due to new technologies allowing for novel formats.”
“Gummies are not going anywhere soon but I do expect that alternative, more creative delivery formats will take away a bit of that market share,” McNamara added. “For example, jelly beans and soft chews are gaining popularity, especially (among) Gen Z and Millennials.”
Common Challenges
For novel delivery formats, special care must be taken to protect ingredients from oxidation, light, moisture, and other factors during shipping and storage. Companies must also consider how the active ingredients will react within the digestive tract once the product is consumed.Absorption remains the number-one factor holding back innovation when it comes to novel delivery platforms, said Ross. “We are seeing consumers drop supplements because they are not seeing and feeling the benefits. In order to find success with innovation, we need to check off all the boxes and bioavailability/absorption is a big one.”
Many nutritional ingredients can’t be added to gummies and other platforms at the same clinically-relevant dose as traditional formats like tablets, capsules, or softgels. Actives may also be less absorbed into the bloodstream.
Controlling the release and timing of an ingredient’s activity is another key challenge. This is especially relevant in supplements that contain two or more ingredients that may interfere with one another. Sustained-release technologies can also overcome challenges related to the time frame of an ingredient’s activity, such as with caffeine or melatonin.
A study published on a sustained-release caffeine ingredient marketed as CaffXtend by Nutriventia, for instance, found that compared to instant-release caffeine, participants who had caffeine gradually enter their system over an extended time period had a better mood and fewer untoward effects typical of caffeine use (The Journal of Dietary Supplements, January 2023).
Top vitamin and supplement brand NatureMade recently added several sleep products to its Wellblends line, featuring a time-release melatonin to address specific night-time complaints such as wanting to sleep longer or being able to fall back asleep in the middle of the night.
While new capabilities are emerging, not all technology platforms are subject to the same quality controls and testing rigor, Meppem cautioned. Further, it’s important to verify that throughout manufacture, sensitive and volatile ingredients themselves were handled according to current Good Manufacturing Practices (cGMPs).
“Quality of manufacture is a considerable challenge, and not readily recognized,” he said. “Manufacturing delivery systems and verifying them with proper quality controls, pharmacokinetic, and clinical validation is not necessarily common. Product stability challenges can be an issue with complex delivery systems.”
The Delivery Technology Landscape
The primary categories of enhancers used in novel delivery formats are emulsifiers, self-emulsifying systems, liposomes, and enzymes/enzyme inhibitors, however, specialist companies have developed several other unique solutions.Liposomes are tiny particles that can encapsulate both hydrophilic and hydrophobic nutrient particles at the microscopic level, and their use has been recognized for improving bioavailability of nutrients.
“There is currently a great deal of interest in liposomes,” said Meppem. “They are more than just an interest or a trend now. However, there is a variety of quality in the market, and not all are properly verified as ‘liposomes,’ but are just labeled that. Liposomes can also assist in overcoming degradation or elimination of an active by the human body’s own immune system.”
Self-emulsifying systems can make certain nutrients compatible in areas they never were before, Meppem added, such as by reducing a dosage needed to achieve clinical efficacy. For instance, Gencor’s AquaCelle technology, a self-micro-emulsifying drug delivery system, was developed to reduce pill sizes for oily ingredients such as fish oil, algal oil, or krill oil.
The company’s compressed powdered oils (CPO) technology can also incorporate these ingredients as powders into two-piece hard capsules mixed with other powders.
Meanwhile, Pharmako offers LipiSperse, which can make lipophilic plant extracts suitable for a range of formats. “LipiSperse technology was originally developed to assist a Spanish customer in including lipophilic curcumin into a ready-to-mix sports nutrition powder. Regular curcumin with magnesium and collagen just forms a sticky orange mess,” Meppem said.
“LipiSperse allows lipophilic powders such as curcumin, resveratrol, silymarin, quercetin, and more to disperse in water. LipiSperse-powered ingredients such as HydroCurc (curcumin), VeriSperse (resveratrol), or Levagen (palmitoylethanolamide) can be used in formats such as effervescent tablets and powders, direct-to-mouth sachets, gels, and gummies, which was previously impossible.”
Emerging Technologies
The prospect of bypassing the digestive tract in delivering nutraceutical ingredients is growing. The company Nutrameltz spent several years developing a technology platform which could allow for buccal absorption of ingredients. Launched in November 2022, the company received 45 natural product numbers from Health Canada, including for 10 of its own branded supplements.According to CEO Suresh Kolla, it took six years to hone flavor masking, ensure ingredients would be intact and viable, and confirm the format could contain 250 mg of any active ingredient in one melt.
“I was truly motivated by several factors,” said Kolla. “The quality of ingredients and research on dietary supplement ingredients continued to grow, with news of ingredient launches and new studies proliferating. In tandem, I have several individuals in my life who have difficulty swallowing pills effectively, which is common. Gummies are the go-to for the pill-averse population, but they also tend to carry some issues of their own—undesirable sugars, and their very texture can interfere with dentition in some individuals. My team and I also researched bioavailability, and found that buccal absorption provided a quicker delivery of the nutritional compounds within the melt.”
Phospholipids, which encapsulate the omega-3 fatty acids in krill, have surfaced as a platform for delivery of other ingredients. Aker BioMarine has developed a phospholipid-based technology platform called PL+, which utilizes krill phospholipids as carriers for other ingredients.
“While there are some solutions in the market that help solve these issues, many are synthetically made, and include a long list of unknown ingredients and don’t offer benefits beyond absorption,” said Ross. “PL+ technology not only improves the absorption of certain ingredients, it also supports healthy cells which deliver health benefits throughout the body. With PL+, we are creating supplements with improved absorption, reduced formulation costs, and enhanced product quality.”
Anything But Conventional
In terms of dosage format, capsule innovation is creating new advantages for this conventional delivery platform.“In the next few years, we expect the advanced capabilities of liquid-filled capsules to have a significant impact on nutraceutical product development,” Navarro said. “Leveraging the versatile polymer options for capsules, as well as technologies like Lonza’s capsule-in-capsule delivery system will also enable advanced combinations and formulations, whatever the ingredient format.”
Navarro noted Lonza’s focus on the sensory appeal of capsules can help to meet heightened consumer expectations. “For some plant-based or botanical ingredients, masking unpleasant tastes and odors can help avoid an off-putting experience for consumers,” she said. “Consumer experience is also key and a product’s dosage form can help a brand stand out on shelves. New flavor and aroma coating technologies can create a favorable sensory experience, and vibrant food-colored capsules offer consumers that ‘Instagrammable’ moment.”
Capsules often offer the greatest control over factors such as moisture, light, and oxygen sensitivity, bioavailability, and taste and odor masking.
“For stability, this primarily comes down to the type of polymer being used. For example, hydroxypropyl methylcellulose (HPMC) capsules deliver greater opacity to prevent UV light penetration, whereas pullulan capsules, made from a compound resulting from a natural tapioca fermentation process, offer low oxygen permeability for oxygen-
sensitive ingredients.”
Tailoring capsule type with the survival and performance of a specific ingredient in mind is another emerging trend, said Navarro. Lonza offers Capsugel DRcaps specifically to protect probiotics as they are exposed to gastric acid.
Lonza also offers a specially-designed capsule with a micro-spray sealing technology in order to prevent leaks and clumps.
Cost-Effective Manufacturing
Improving the functionality and bioavailability of ingredients can result in reduced costs of manufacturing.“Smaller batch sizes or runs are more cost-effective, not necessarily for the contract manufacturer, but for some brands,” said Meppem, “so using Pharmako’s CPO technology to move oils into powders allows smaller batches of two-piece hard capsules rather than softgel capsules. These formats also more easily cater to vegan or vegetarian consumers. AquaCelle has published human pharmacokinetic data validating it increases the absorption of key actives such as omega-3s, coenzyme-Q10, and lutein. Decreasing a dose by up to six times is true cost-saving, and a much better use of resources.”
According to Navarro, capsules are a cost-saver because they eliminate the need to use excipients that would otherwise be needed for machinability or powder flow. Smaller batches and pilot batches at the front end of product development are another means of reducing waste and lowering cost.
“Capsule design, as well as manufacturing and equipment technology can also help cut back on overfilling, which conserves ingredient resources and reduces costs,” she said, adding that trimmings from some gelatin two-piece capsule manufacturing processes “can be reused and re-melted to rejoin the production cycle, diverting a potential waste stream and again saving valuable resources.”
In addition, equipment that allows for small batch runs during product development allows brand owners or contract manufacturers to perform pilot batch programs and streamline their production processes, while reducing capsule failure rates before full production, Navarro said.
