Issue link: https://www.e-digitaleditions.com/i/446555
12 January 2015 Tablets & Capsules Another study presented at the AAPS meeting compared how hard capsules made from different polymers performed in drug delivery via the vagina [4], a method that, like ocular delivery, shows promise in overcoming the blood-brain barrier. The study's authors stated that many new products that employ hard capsules for vaginal applications failed to account for the capsule's nature or functionality. Their tests, conducted using a texture analyzer, showed that pullulan capsules— Capsugel's Plantcaps—provided rapid content release through quick disintegration. The pullulan also helped keep the capsule in place through strong bio-adhesion. Micro-dosing Capsules also have applications in pulmonary delivery, typically in dry powder inhalers (DPIs). Capsugel presented data about how different hard capsules performed in different DPIs [5], and Qualicaps, a capsule supplier based in Whitsett, NC, offered posters that evaluated how capsule composition (HPMC versus gelatin) and temperature affected puncture performance [6-8]. [Editor's note: For more information about nasal and pulmonary delivery, see Tablets & Capsules' sister magazine Inhalation: www.inhalationmag.com.] Whatever capsules are used in DPIs, it's critical that they contain the right powder dose. Until recently, that usually meant filling them using a dosator-style capsule filling machine, because tamping-style machines were not really suitable. Bosch, known best for tamping machines, will begin offering dosator-style machines this year. It has also developed a new technology, called a vacuum dosing wheel. It dispenses as little as 1 milligram of powder at a standard deviation of ±2 percent and can fill capsules with as much as 200 milligrams. It can also micro-dose other types of powders. "We see more and more applications in dosing pure APIs and in dosing very small formulations," Opitz said. "For [fills] up to 100 milligrams, it can be very accurate, this wheel technology. It's completely different from tamping pins," he said, noting that immediate-release formulations are an appropriate application. "If you have a good soluble API, why should you go the way of formulation, where you have to test the interactions between the excipients, API, and capsule shell? Why don't you fill the API directly into the capsule? More and more, we're seeing requests from formulators who are thinking about putting just API in the final product." Originally, filling capsules with neat API was a method to accelerate clinical trials, and one of the first micro- dosing systems to take hold was Xcelodose, a technology that Capsugel acquired in 2005. Another micro-dosing system, Quantos, was introduced in 2008 by Mettler- Toledo, Columbus, OH. Opitz, who worked at Capsugel until 2013, called the Xcelodose "fantastic," because it helps bring products to market quickly. But the dosing wheel is a better fit for scale-up and large-scale production, he said. "We improved the system so much in the last year, 2014, and it can handle a big range of different kinds of APIs or formulations in small amounts. The wheel allows you to adjust quantities, so during drug development, you can play around with different quantities by adjusting it." Softgel science Softgel capsules offer formulators additional flexibility. In October 2012, Patheon acquired Banner Pharmacaps, the world's second-largest pharmaceutical business dedicated to softgel formulations. "Banner gave us added value," said Anil Kane, executive director and global head of formulation sciences at Patheon. "We now can provide our clients with a softgel dosage form for delivery of immediate-release, controlled-release, as well as areas for pediatrics, geriatrics, and other special types of delivery, such as enteric-release softgels." Technologies include EnteriCare enteric-release softgels, Versatrol controlled- release softgels, Solvatrol softgels for enhanced solubility, LiquiSoft pediatric softgels, Chewels chewable forms, and twist-offs. The twist-off capsules can hold a large liquid dose, which is squeezed into the mouth. They help deliver medicine to pediatric and geriatric patients, as well as others who have difficulty swallowing tablets or capsules. Kane said the special equipment, excipients, and expertise that softgels require aren't an issue for customers. "They prefer to outsource this to specialized groups. I don't think it's the best use of a firm's in-house skill sets to develop a small number of products in a specialized dosage like a softgel. I think it's advantageous to outsource to a specialist rather than training individuals and investing in this in-house." It may even be faster to use a softgel instead of a liquid- filled hard capsule to get new products to market. "We can do a very small, benchtop, proof-of-concept in softgels," Kane said. "We can also take softgels from phase 1 through to later phases of development and on to commercial much faster because the vehicle is the same," he said. "So the scalability is much faster, and the output can be much higher than the two-piece liquid-filled hardshell, which needs additional steps, such as banding, sealing, and drying. We see a lot more benefits with the softgel." Bosch's vacuum dosing wheel dispenses as little as 1 milligram of powder at a standard deviation of ±2 percent. Photo courtesy of Bosch