Fast-melt or quick-dissolving formulations pose certain challenges in excipient selection. "APIs that have an extreme sensitivity to water may pose problems for API stability since the excipients usually contain water in the amount of 4–5% by weight," says Widmaier. "In this case, it can help to coat the API to protect it from the water present in the excipient."

The pressure on the API during tableting is another consideration. "The excipient should diminish the pressure on the coated API granules, so that these granules are not being damaged during compression to the final tablet," says Widmaier.

The filler and binder may also affect the ODT. The filler should dissolve readily in water and saliva without increasing the solution's viscosity. "Otherwise, the entrance of water into the tablet will be delayed, and the disintegration time increases," explains Widmaier. "For the binder, quick dissolution diminishes the speed of disintegration."

Isomalt is used with ODTs formulated through direct compression. "The number of fillers and binders in this area is limited because these bulk excipients have to fulfill special requirements from a technology and sensorial view," says Fritzsching. Because galenIQ is based on sucrose, it offers taste-masking potential, thus adding functionality to the formulation.

Other producers point to limitations in attaining multifunctionality. "The concept of an excipient product that provides two functions, such as binder and disintegration, is appealing," says Bee. "However, there are usually compromises in the overall performance and a loss in formulation flexibility. The excipient is not as effective at doing one of the functions as effectively as an excipient that provides a single function." ISP provides "Polyplasdone" (crospovidone) for ODTs.

Controlled-release formulations. Excipient producers are also targeting excipients to improve the performance of controlled-release formulations. "Direct compression is the lowest cost, quickest-to scaleup process for controlled-release formulations," says Kacee Ender, pharmaceutical applications development specialist in the pharmaceutical excipient research and development group of Dow Wolff Celullosics, a business unit of the Dow Chemical Company (Midland, MI). Dow Wolff Celullosics recently introduced two new hypromellose products for direct compression of controlled-release matrix oral dosage forms. "Methocel" K4M and "Methocel" K100M premium DC grades are viscosity grades designed to improve powder flowability while maintaining compressibility, tablet hardness, and controlled-release performance, says Ender.

JRS Pharma's "ProSolv SMCC" (silicified microcrystalline cellulose (MCC) is a multifunctional exicipient that can be used in controlled-release applications. "The surface roughness and colloidal silicon dioxide (CSD) adds flow, but it allows the excipient to be more effective in producing dry-blended, ordered mixtures, which in turn improves content uniformity," explains Guy. "The product is differentiable from MCC–CSD blends in its interaction with water. Several companies have used this property for matrix-controlled release systems."

Patricia Van Arnum is a senior editor at Pharmaceutical Technology, 485 Route One South, Bldg F, First Floor, Iselin, NJ, 08830, tel. 732.346.3072, pvanarnum@advanstar.com

References

1. "Excipients in Pharmaceuticals" Report No. PHM010E, BCC Research (Norwalk, CT, 2006).

For more on innovation in excipients, see the online exclusive: "Tracking the Potential of Excipients"