Choosing the Best Dosage Form

If necessity is the mother of invention, then it’s easy to understand the recent wave of improvements in dosage form technology. Most nutritional supplements must be taken regularly to be effective, so products that taste bad or spoil are likely to fade from store shelves in no time. Fortunately, new technology is helping manufacturers make tablets, capsules, and liquids that offer nutritional benefits without sacrificing taste and quality.

A BEADING FRENZY

Tablets, one of the world’s most popular dosage forms, are leading the way. Manufacturers and ingredient suppliers have been busy creating directly compressible (DC), beadlet, controlled release, and even effervescent forms of popular supplement components. Manufacturers increasingly favor DC and beadlet ingredients because they usually require fewer processing steps than other forms of materials and help manufacturers create smaller tablets, which improves compliance.

Raw materials often exist in forms that are difficult to put into tablets. Manufacturers have a range of processes at their disposal that alter the physical characteristics of powdered ingredients. But these processes also have their drawbacks. Granulation, for instance, improves flow and bulk density, but it can also be time consuming and labor intensive or require specialized equipment. Alternatives, such as DC and beadlet ingredients, are often seen as solutions because they don’t require additional modification and they reduce the need for overage, making products more cost-effective. The current selection of DC and beadlet ingredients, while limited, is growing.

For instance, BASF Corp.’s (Florham Park, NJ) new CoQ10 ingredient, a stable and fast-acting 10% DC powder, is intended to help manufacturers create formulas using this notoriously hard-to-handle nutrient. The company, which launched the ingredient in May at this year’s SupplySide East show in Secaucus, NJ, also released a solubilizate form of CoQ10 for use in softgels. “By offering two new formulations for multivitamin tablets and softgel capsules, BASF is uniquely positioned to serve the needs of the dietary supplement industry,” said Martin Jager, PhD, BASF’s director of strategic marketing and human nutrition.

Direct compression isn’t just for vitamins. In 2002, Finzelberg (Andernach, Germany) and Penwest (Danbury, CT) created RediRun, a line of DC botanical extracts that includes St. John’s wort, ginkgo, and horse chestnut. JRS Pharma (Patterson, NY) acquired RediRun as part of Penwest’s excipient business in 2003. Newer examples of DC herbs include SoyLife DC from Acatris (Minneapolis), which launched in January, and Kemin Europe’s (Herentals, Belgium) tablet-grade version of FloraGlo lutein.

Beadlets are also proving to be popular dosage vehicles. In the past, beadlets were often composed of gelatin, but the current interest in vegetarian ingredients has led to many new offerings. For example, BetaTab 20% S, a vegetarian beta-carotene beadlet from DSM Nutritional Products (Parsippany, NJ) launched in January, and AstaPure, a vegetarian astaxanthin beadlet from Algatechnologies (Eilot, Israel), debuted in March. The latest step in beadlet technology may be the cobeadlet, which embeds several nutrients within a single protective matrix. According to Udi Alroy, marketing director for LycoRed (Beer Sheva, Israel), which offers cobeadlets that contain multiple carotenoids, the new technology lets manufacturers create smaller and less-expensive tablets by eliminating the need for overages that are normally factored in for unstable ingredients. “Cobeadlets simplify the manufacturing process, since only one product needs to be handled, whether it is weighing, inventory management, or accounting,” Alroy explains.

Other improvements, such as controlled-delivery and effervescent technology, are also making tablets more palatable to consumers. In May, researchers at the North American Research Conference on Complementary and Integrative Medicine held in Edmonton, AB, Canada, reported that they were able to detect immune system changes in volunteers after consumption of Immunobiotix tablets manufactured by Nutraceutix (Redmond, WA). Those tablets use the company’s Bio-Tract controlled-delivery technology to safely convey probiotics into the gastrointestinal tract. Like CoQ10, probiotic supplements can be difficult to formulate because they are sensitive to changes in light, moisture, and acidity.

Meanwhile, effervescent tablets, which are also sensitive to environmental changes, are benefiting from new “can-do” technology developed by Süd-Chemie (Belen, NM). Süd-Chemie recently created new, scented canisters that protect fragile tablets while disguising any objectionable odors with pleasant scents like orange and lemon. According to Mark Florez, marketing manager at Süd-Chemie, the company’s Aroma-Can canisters are manufactured using generally recognized as safe (GRAS) materials. The canisters are intended for use with or without desiccants and may be inserted using standard equipment.

HARD SHELLS FOR LIQUIDS

Thanks to the popularity of products like omega-3s and cold medicines, liquid-filled capsules are making a comeback. While their ascendancy is relatively recent, liquid-filled capsules are actually among the earliest dosage forms for pharmaceuticals. According to Brian Jones, a scientific advisor for Shionogi Qualicaps (Whitsett, NC), a French scientist patented the first medicinal capsule in 1834. The capsule, a gelatin bubble injected with liquid, was later superseded by the invention of the first hard-shell capsule in Paris in 1846. Jones notes that early capsules were intended to hold liquids and pastes, rather than powders, which didn’t become common until the early 20th century. Now, things have come full circle, as consumers and manufacturers alike tend to prefer the increased bioavailability of liquid ingredients.

The resurgence of liquids has led to improvements in capsule-filling equipment. For instance, the Liqfil Super 40, featured by Qualicaps at this year’s Interphex convention in March in New York City, was redesigned to offer several new options. The machine, which fills powders, pellets, beads, pastes, oils, and liquids at speeds of 40,000 capsules per hour, now has a hot-air purge system to prevent leakage and bubbles, along with an add-on cooling tower to protect capsules.

Machines that combine filling and sealing operations are one of the newest developments for capsules. At Interphex, Qualicaps unveiled a new lab-scale machine that fills and seals liquids into two-piece capsules at speeds of up to 3000 capsules per hour. For larger projects, Capsugel’s (Greenwood, SC) Liquid Encapsulation Microspray Sealing (LEMS) production-scale machine seals up to 30,000 capsules per hour.

No discussion of capsules can be complete without mentioning softgels, however. Last year, Soft Gel Technologies (Los Angeles) announced that it had developed CoQsol-CF, a crystal-free, patent-pending softgel formulation of CoQ10. The CoQ10 ingredient joined the company’s growing line of products created specifically for softgels, including Injuv, a low-molecular-weight form of hyaluronic acid, and a softgel version of the cardiovascular health ingredient Sytrinol.

A CHIP OFF THE OLD BLOC

Finally, purely liquid supplements pose several challenges for beverage manufacturers, who often are forced to juggle competing demands for improved flavor, longer shelf life, and the extra space required for filling equipment.

Krones AG (Neutraubling, Germany) kept those concerns in mind when it constructed a cold-temperature aseptic filling system, dubbed the Rainbow, for Bavarian dairy Molkerei Heinrich Gropper (Bissingen, Germany). At an April 4 ceremony at the Anuga FoodTec trade fair in Cologne, Krones received the prestigious FoodTec Gold Award from the German Agricultural Society (Frankfurt/Main, Germany) for its scientific efforts.

Krones designed the Rainbow to fill up to four flavored dairy products simultaneously. Four gas-pressurized product tanks hold the beverages, which enter the filling valves via a four-channel rotary media manifold. The filler assigns one flavor to every fourth valve, enabling Gropper and other beverage producers to keep up with demand for dairy-based drinks, which are expected to hit $3 billion in U.S. sales alone in 2006.

The filler’s aseptic design helps prolong shelf life, an important consideration for dairy beverages. Krones based the Rainbow on an existing volumetric filling system but added two improvements: a weighing cell that defines fill quantity by weight, and a BLOC synchronization of the filler with a disinfection module that uses gaseous hydrogen peroxide to sterilize the bottles. A visual inspection system reinforces quality control, further ensuring shelf life, by verifying fill levels and closure applications.

The system’s efficiency is enhanced by the addition of a Krones Sleevematic labeler, which applies four different shrink film sleeves at a speed of up to 18,700 containers per hour. In the shrink tunnel, special quick-release steam nozzles, also designed by Krones, can be matched to various bottle contours and require minimal changeover time. The sleeves enhance bottle appearance while also acting as a tamper-evident seal.

One of the filler’s most valuable assets is the efficient way it conserves space. The Rainbow fills and labels up to four different kinds of products simultaneously but requires fewer pieces of equipment and less manufacturing area than other filling systems. Moreover, a Krones Accutower buffering system that activates in the event of a bottling-line malfunction helps preserve a small footprint by temporarily storing bottles in a coaxial track that spirals upward.

Germany is a long way from Ireland. But as consumer interest in flavored dairy beverages and other liquid supplements continues to grow, manufacturers looking for a pot of gold may find it-or something close-underneath the Rainbow.