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."
Beneo–Palatinit (Mannheim, Germany) markets a high-solubility grade of "galenIQ 721" (pharmaceutical-grade isomalt) for ODTs. Beneo–Palatinit
introduced galenIQ two years ago as a filler and binder. The product is derived from sucrose. Through enzymatic transglucosidation,
sucrose is converted to the disaccharide 6-O-α-D-glucopyranosyl fructose, a reducing compound, which is hydrogenated. This
process results in the stereoisomer disaccharide alcohol 1-O-α-D-glucopyranosyl-D-mannitol dihydrate and 6-O-α-D-glucopyranosyl-D-sorbitol
in an approximate equimolecular mixture, explains Bodo Fritzsching, head of pharmaceutical sales and technical services at
Beneo–Palatinit. Through additional processing, the ratio of the two molecular components can be varied, resulting in grades
with different solubilities. The lower soluble galenIQ 720 (solubility 24.5 g/100 g at 20 °C) is used in sublinguals that
dissolve slowly in the oral cavity or for swallowable tablets that erode within several minutes. The other grade, galenIQ
721 (solubility 41.5 g/100 g at 20 °C), shows good disintegration properties and can be used with crospovidone for fast and
very fast disintegrating tablets.
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"
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