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48 April 2014 Tablets & Capsules R&D groups are often under pres- sure to shorten a product's time-to- market, and are thus demanding more functionality and performance from excipients and coatings. This quest for performance is espe- cially important when the drug prod- uct includes one or more moisture-sen- sitive active pharmaceutical ingredients (APIs) because potential problems associated with these APIs include poor flow properties, variable dissolu- tion rates, and chemical/physical insta- bility (hydrolysis, color change, etc.). As a result, formulators are seeking cost-effective excipients for the tablet core that minimize moisture sensitivity and film coatings that provide a mois- ture barrier. In fact, the stability of moisture-sensitive drug products depends on how well R&D groups address key formulation and processing variables, including core excipients, film coatings, and process parameters, as well as packaging materials. Tablet core During excipient selection, it is crit- ical to differentiate water activity from moisture content. Core excipients with low water activity are preferred because they protect APIs from hydrolytic degradation by tightly binding moisture in the core. Total moisture content, typically measured by loss-on-drying, does not distinguish between bound moisture and unbound moisture. A better measure is water activity, also known as equilibrium rel- ative humidity, which quantifies the unbound water. For example, one of my company's products, Starch 1500 has a high moisture content but low water activity. Therefore, it equili- brates slowly when exposed to mois- ture and may, preferentially, bind the moisture and thereby prevent the water from interacting with the API. As a result, it is beneficial to use Starch 1500 in formulations that include moisture-sensitive APIs to ensure sta- bility. The resulting robust formula- tions help lower costs by reducing the need for special processing and/or expensive packaging. Process settings Parameters of the film coating process—spray rate, airflow, and inlet- air temperature—can all affect mois- ture content. Depend ing on the coat- ing setup, the process of applying an aqueous film coating may maintain or even decrease the mois ture content of the product, which shows that the process is suitable even for moisture- sensitive products. Research also shows that adding a pre-drying step to the pro cess significantly influences the fi - nal moisture content of coated tablets. Film coating chemistry Of course, the coating constituents are the major factor in protecting against moisture, and poly vinyl alco- hol (PVA) is gaining popu larity over HPMC as a film coating polymer because it: • Provides good film properties from the polymeric solution • Has global regulatory acceptance • Results in films with very good barrier properties, especially against moisture and oxygen • Supports relatively low-viscosity coating solutions, typically with >20 percent solids, enabling the polymer to be used at higher con- centrations and raising cost-effec- tiveness and productivity • Produces strong films that adhere well to tablet surfaces, enabling excellent logo definition, even with challenging tablet designs • Improves bulk tablet flow proper- ties, enhancing packaging speed and saving time. Indeed, PVA-based film coatings are optimized to provide the lowest possible moisture vapor transmission rate while providing all the conve- niences of a one-step film coating system. In addition, more recently developed PVA- and acrylic-based film coatings (Opadry 200, for example) can be used with solids concentrations as high as 25 percent, which ensures excellent coating productivity and moisture barrier properties. It has been proposed that hydrogen bonding of the -COOH groups of acrylic acid with the -OH group of the PVA pro- vides the mechanism for enhanced moisture barrier properties of the coat- ings. Furthermore, PVA- and acrylic- based film coatings can be made with- out polyethylene glycol (PEG), which addresses the instability and color fad- ing that certain APIs can induce due to the oxidation chemistry or mobility of PEG under high-temperature, high- humidity environments. Conclusion Selecting the right excipients can reduce a product's hydroscopicity and water activity, and low-water- activity excipients can help you for- mulate drug products that contain moisture-sensitive APIs into robust and stable tablets. Selecting the right excipients—including advanced film coating products—can also substan- tially reduce total process time and costs, enhance quality and, ulti- mately, meet stability challenges. T&C [Editor's note: To comment on the Back Page, visit www.tabletscap sules.com.] Pankaj R. Rege, Ph.D., MBA, is director for market development at Colorcon, 415 Moyer Boulevard, West Point, PA 19486. Email: prege@colorcon. com. Before joining Color- con, Rege held various positions in for- mulation development, technology trans- fer, and project management. b a c k p a g e Formulating tablets containing moisture-sensitive actives k-BP_48_q-Backpage_72 4/3/14 2:59 PM Page 48