Exploring tablet and capsule technologies.
There are some who believe bigger is better. Dietary supplement manufacturers probably would disagree.
A pill with a mega-sized serving of active ingredients might sound good on paper, but if the user can’t swallow it, then it defeats its own purpose. Yet, a pill that is too small often cannot deliver an efficacious level of nutrients and eventually, users will give up on products that don’t do their job.
What’s the happy medium? Tablets and capsules that are easy to swallow (almost) no matter what their size. Also, it wouldn’t hurt if these supplements could provide superior bioavailability and measured release times-and any other innovations to take delivery to the next level.
A new firm, founded in 2010 by Rick Hardy and his wife Lindsay, is so avid about the possibilities that it is named Easy2Swallow. Located in Lake Barrington, IL, the company produces a line of supplements for those suffering from dysphagia, a swallowing disorder that affects people of all ages, but particularly those over 50. (Read more about dysphagia on page 24.)
Mike Hardy, vice president of Easy2Swallow, describes the firm’s line as “intelligently designed, 40 to 70% smaller by weight, and coated for easier swallowing.” Elements of the line include both tablets and capsules. Among the varieties are calcium with vitamin D3, vitamin C, omega-3 oils, men’s multivitamins, women’s multivitamins, prenatal vitamins, glucosamine, melatonin, flush-free niacin, folic acid, and coenzyme Q10.
The Hardys note that the company grew out of their personal experience. As a cancer patient undergoing chemotherapy and radiation treatment, Lindsay found it difficult to swallow popular multivitamins, which she says could weigh between 1000 and 1500 mg-about the size of a kidney bean. They reasoned that smaller might be better.
On the capsule supplier’s side, at Greenwood, SC–based Capsugel, products include the following: Coni-Snap hard gelatin capsules, used to mask taste and odor in a unit that is considered easy to swallow; Vcaps and Vcaps Plus vegetarian capsules that appeal to consumers with special religious, health, dietary, and lifestyle requirements; NPcaps, made of pullulan, a material offering the best oxygen barrier and therefore “ideal for organic ingredients” or to “mask even pungent ingredient odors;” and Licaps liquid-filled capsules, designed to help improve bioavailability as well as contribute to longer shelf life.
Mark Vieceli, director of sales, marketing, and business development, says Licaps are suitable for multi-release and time-release products, two formats growing in popularity with consumers. There are two forms of Licaps-beads in a liquid-fill capsule and a capsule within a capsule.
“In beads in a liquid-fill capsule, the liquid dose is designed to offer quick release of an ingredient while the beads provide for a controlled or delayed time release,” says Vieceli. “The thickness of a bead’s coating can be changed so that some beads dissolve as soon as the capsule ruptures, while other beads dissolve later.”
Vieceli continues: “A capsule within a capsule is a similar delivery innovation for combination products. It works for incompatible ingredients or ingredients that would separate if mixed together. Probiotics is a product category that can benefit from this approach-more specifically, a probiotic [like Capsugel’s Pre-Pro Combo] that combines a prebiotic and probiotic in one.”
Licaps OceanCaps are another variation specifically aimed at carrying krill oil, which Vieceli calls “the rising star of the omega-3 supplements.” The Capsugel executive says, “Softgels have long been a primary delivery vehicle for fish oils, but because krill oil contains the highest concentration of phospholipids, it can prove challenging for softgels to remain leak-free over time. Hard gelatin capsules with a lower moisture level, however, hold up. And because they are less permeable to oxygen, hard gelatin capsules successfully mask krill oil’s extremely pungent odor, without the need to add scent as a masking agent.”
Capsugel has also introduced yet another specialized product-DRcaps, described as “a vegetarian capsule with unique properties that slow down capsule opening after swallowing.” The company says DRcaps are made from hydroxypropyl methylcellulose (HPMC) and disintegrate more slowly than conventional gelatin or HPMC capsules. This helps protect active ingredients in the capsules after swallowing. The threat of early activation caused by stomach acid is lessened, and without adding synthetic chemicals, solvents, or other coating ingredients. Vieceli cites in vitro studies showing that “capsule contents are protected for at least 30 minutes at a gastric pH of 1.2 and release fully at an intestinal pH of 6.8.” The appeal to manufacturers is the potential to eliminate a coating step, thus cutting production costs and time.
Keith Hutchison, PhD, Capsugel’s vice president of research and development, has stated to the press, “This is not an enteric capsule in the pharmaceutical sense, but it provides very effective protection for ingredients in the stomach and relief from adverse tastes as well. And while there are clearly consumer benefits, DRcaps also make it easier for our customers to launch products rapidly.”
Focusing on softgel capsules, Soft Gel Technologies Inc. (SGTI) is a Los Angeles, CA–based full-service contract manufacturer. Steve Holtby, president and CEO, says softgel capsules offer many benefits over other delivery systems. They are “easier to swallow than tablets, have the ability to mask odors and unpleasant tastes, and may improve patient compliance. They readily dissolve in the gastric juices of the digestive tract and may enhance the bioavailability of poorly soluble active ingredients. Softgel capsules protect formulations from reactions with light and offer protection to oxygen-sensitive ingredients.”
Further, says Holtby, “There are wide varieties of shell colors, shapes, and sizes available to offer product differentiation in the market.” Not to mention that these attributes help consumers recognize which nutrients they are taking at any given time.
The SGTI product lineup includes the following: CoQsol, a softgel formulation of CoQ10 that offers enhanced bioavailability; CoQH-CF, a clinically proven reduced form of CoQ-10 (ubiquinol) that demonstrates superior bioavailability (this is a targeted antioxidant solution providing a stabilized and protected form of Kaneka QH ubiquinol in a softgel using the firm’s crystal-free technology); EZ Mega 3, an “extremely stable and deodorized fish oil concentrate” that provides omega-3 essential fatty acids in an easy-to-swallow capsule that is odorless, neutral in taste, and contaminant-free; GlucoHelp, a fast-acting, clinically studied banaba leaf extract, standardized to 18% corosolic acid, for the maintenance of healthy blood glucose levels; Injuv, a naturally derived hyaluronic acid complex nutricosmetic for skin and joint health (its patented enzyme-cleaving process allows it to have a low molecular weight for better absorption); Perluxan softgels, a supplement primarily used to support joint health and soothe aches from overexertion of everyday activities (the formula includes a proprietary hops resin extract that is standardized to contain high concentrations of alpha acids clinically demonstrated to reduce pain-causing compounds in a short time with a low dose); and Smart PS, softgels that feature an exclusive fluid dispersion phosphatidylserine material that is said to have “significantly enhanced stability for maximum brain benefits.”
Sabinsa Corp., with offices in East Windsor, NJ, and Payson, UT, offers hard gelatin and veggie capsules, as well as numerous tablet variations, including uncoated, film-coated, and enteric-coated tablets. In August, the company announced a new line of bi-layered, multi-release tablets called Integrated Nutritional Composites (pictured above).
“Bi-layer tablets are common in pharmaceutical product ranges,” says Shaheen Majeed, Sabinsa’s marketing director. “For the nutraceuticals industry, it is pretty unique. While it is out there, it may for an ‘appeal’ basis.” But, he says, this is where Sabinsa has differentiated itself, by truly focusing on the efficacy benefits bi-layer tablets can provide.
For formulation/marketing ease, Sabinsa is offering the tablets in various condition-specific versions using some of the company’s most in-demand branded ingredients. Blood Sugar Support INC Actives contains Sabinsa’s Silbinol (pterostilbene 5%, 30%, or 90%), cinnamon extract, zinc monomethionine, and Sabinsa’s BioPerine black pepper extract that enhances ingredient bioavailability. Other offerings include: Weight Management INC Actives, featuring Sabinsa’s ForsLean Coleus forskohlii, GarCitrin Garcinia cambogia, and BioPerine; Heart Health INC Actives with policosanol and niacin; Heart Health + INC Actives, with L-carnitine, beetroot extract, policosanol, and niacin; and NiLitis SR INC Actives, containing Sabinsa’s Boswellin Boswellia serrata and Curcumin C3 Complex (curcuminoids 95%), as well as ginger extract. (The company has even completed a clinical study on NiLitis, which showed that this unique formula, without any glucosamine, showed better results compared to a leading joint-support product on the market, in terms of improving walking distance.)
“We have taken ingredients that work best in different release profiles and have been able to formulate based on that,” Majeed says. “For example, you may want a joint-support tablet to do, on one layer, a rapid release or simply a regular release, while the other layer can help with a sustained-release profile for lasting effects throughout the day or night.”
“With our line of patented ingredients and formulation expertise, we can innovate some rather unique formulas,” he adds. In addition to these predetermined formulas, the company can also create completely customized formulas for companies.
According to Sabinsa, the bi-layer design allows stable delivery of active ingredients that otherwise might be incompatible or difficult to formulate together. Most powder ingredients should work, and Majeed says that so far, the company has not come across any prohibitive tableting issues.
When asked about compatibility issues when including two formulas in one tablet, Majeed responded: “Active ingredients requiring different basic manufacturing conditions can be incorporated into a bi-layer tablet. For example, one of the items in a formula is prepared by lyophilization [freeze drying], while all others can be prepared by conventional technique. [Although] the lyophilized version cannot handle the regular tablet-making steps, it can still be included in the single-tablet form using this bi-layer technology.”
Another example he gives: “In some instances, an analgesic [painkiller] and anti-inflammatory components require different release profiles-the analgesic fraction immediately, and the anti-inflammatory components at a slower rate.” The bi-layer tablets would be ideal for this type of application, he says.
And, of course, these tablets offer novelty appeal. “When you look at your average consumer, I think it’s safe to say that they would like to try something new,” says Majeed. “If it ‘clicks’ with them, and if it eventually shows results, [a concept] will last a long time. While many single-layer tablets have achieved this, there are those retailers and consumers looking for the next innovation. In our industry, this is it.” Additionally, he notes, bi-layer tablets offer consumers the possibility of having to take fewer tablets, “which appeals to a lot of people.”
At Nutricap Labs in Farmingdale, NY, the line consists of gelatin and veggie capsules along with chewable tablets, sublingual tablets, lozenges, and bi-sect tablets. Jason Provenzano, president and founder, says time-release tablets and enteric-coated tablets that pass through the stomach to be digested in the intestine are relevant examples of improved supplement technology.
Nevertheless, Provenzano acknowledges room for further improvement. He says, “Tablets can unpredictably become brittle and break before the projected lead times due to oxidation, time, and temperature. These reactions can also cause bottle expansion. While many times this is the fault of an ingredient in the product, I have not seen a coating that can prevent this 100% of the time.”
This past April, BASF, with U.S. offices in Florham Park, NJ, and X-Rite, located in Grand Rapids, MI, said they were collaborating on “an easy to handle on-site approach to color-coating tablets.” The new procedure combines BASF’s Kollicoat IR Coating Systems with X-Rite’s ColorEye XTH Handheld Spectrophotometer.
BASF says its Kollicoat IR Coating Systems rely on a modular system of seven base colors that are designed to combine easily to produce instantly recognizable tablets in hundreds of different shades. X-Rite says its XTH ColorEye Handheld Spectrophotometer is a practical, portable device that accurately measures tablet and capsule colors. In a joint statement, the companies said, “This approach replaces complex logistic processes and ensures that in-house formulation knowledge remains confidential.”
Natoli Engineering Company of St. Charles, MO, makes no vitamins or dietary supplements-not even the ingredients they contain. Instead, since 1973, when it was founded by Carmelo Natoli, it has been delivering tablet-compression machines and services to pharmaceutical, nutritional, confectionery, industrial, and veterinary manufacturers around the globe. Along the way, it has amassed a wealth of understanding about tablet and capsule technology, and this knowledge is reflected in Natoli’s 184-page catalog, which includes more than 1500 items. Among products the company is currently showcasing is a light-induced fluorescence (LIF) sensor. During powder blending, it helps to ensure blend uniformity.
Recent product introductions from Natoli include the NP-500 Series, a double-sided, single-footprint rotary tablet press that’s designed to compress tablets requiring extra fill and extended dwell time; and the semiautomatic NP-RD10A, which, like the previous manually operated version, is a single-station, benchtop tablet press that can be used for laboratory research and development when only small samples are available for testing.
Dale Natoli, vice president, has called the Natoli TM-II punch inspection and tool management system “perhaps our most interesting product.” This efficient inspection system utilizes non-contact laser technology and accommodates multitip tooling. It also features a database that manages critical tooling information related to vendor inspection, measurements, wear analysis, tablet-production history, purchase orders, drawings, steel and machine type, storage locations, and more.
In a June 2011 interview that appeared in Innovation in Pharmaceutical Technology (IPT), Natoli suggested that the most common day-to-day problem encountered in tablet production is granulation adhering to the tool face, commonly known as “sticking.” It is not uncommon for tablet manufacturers to struggle through compressing a batch of sticky product and sometimes-due to the severity of the sticking-to be unable to compress any tablets at all, he indicated.
Natoli identified tablet-press cleanliness and proper maintenance as the most important factors needed for consistent tablet production. Conversely, he stated, the acceptance of multitip tooling has been the most important contributor to tableting speed. In the article, he said, “The first rotary tablet presses produced 400 to 600 tablets a minute, whereas the modern tablet presses of today can produce more than 100,000 tablets per minute. Innovation is simply matter of time.”