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eye on forces that would—if applied to con- ventional ODT excipients—reduce porosity and thus diminish tablet per- formance. In addition, Granfiller-D (grade GNF-D211) has a US drug master file (DMF) and is used in mar- keted drug products in Japan. Powder properties and basic characteristics Granfiller-D includes four excipi- ents listed in the USP, EP, and JP: man- nitol, crospovidone, carmellose, and microcrystalline cellulose. These are coprocessed using a water-based gran- ulation method, resulting in two grades of the excipient that differ only in particle size: GNF-D211 has parti- cles of 100 microns, and GNF-D215 has particles of 160 microns (Table 1). To make ODTs using this copro- cessed excipient, you add one or more active pharmaceutical ingredients (APIs), a flavoring agent, a sweetener, and a lubricant; blend them; and then compress the mixture on a standard tablet press. Tablet formation and dis- integration are typically satisfactory without the addition of binders or dis- integrants, which simplifies ODT for- mulation and manufacture (Figure 1). Differences from conventional concept The coprocessed excipient also accepts large doses of API while main- taining high hardness and rapid disin- tegration. Due to this high dose capacity, the excipient also gives you the flexibility to formulate controlled- release tablets, mask bitter tastes, and stabilize APIs. Of course, the excipient also disin- tegrates rapidly. That's because the particles themselves act as the water- intake route—a new concept for ODT excipients—as does tablet porosity, which is the conventional approach and which requires tabletting at low compression force. No other direct- compression ODT excipient provides faster disintegration. In one case, the disintegration time of small ODTs made with Granfiller-D was equivalent to that of lyophilized ODTs that disin- tegrated in 5 seconds. The excipient also allows the appli- cation of high compression force, although high force is not required to form a proper tablet. An assessment of placebo tablets made using conven- tional ODT excipients and com- pressed at 40 to 50 newtons showed Tablets & Capsules March 2016 37 Takahiro Hiramura and Makoto Narushima Daicel excipients This edition of the column assesses the attributes and applications of a copro- cessed excipient for the direct compression of orally disintegrating tablets . Developing orally disintegrating tablets (ODTs) is a worldwide trend, but it's particularly popular in Japan, where formulators at innovator com- panies, generic drug companies, and contract manufacturers compete to develop new ODTs. In fact, Japan accounts for the largest share of ODTs in the world [1]. Traditionally, manufacturing ODTs was a wet process that required special manufacturing equipment. Lyophili- zation is one example. In recent years, however, new excipients and excipient blends have enabled manufacturers to produce ODTs using conventional equipment, i.e., blenders and tablet presses. When compressing ODTs, the main concern is ensuring the forma- tion of water absorption routes, which typically means tabletting at a low compression force to create highly porous tablets that retain sufficient hardness to withstand handling. Meeting these seemingly contradic- tory product attributes—high porosity and high tablet hardness—requires using excipients that can achieve high tablet hardness even when compressed with low compression force. One such product is Granfiller-D, a coprocessed excipient that comprises a specific ratio of compendial excipients that have undergone a proprietary granulation method [2, 3]. Because Granfiller-D's particles themselves pro- vide the water-intake route, the excipi- ent can be tabletted at compression Table 1 Properties Median particle size (microns) 100 160 Density (g/cm 3 ) 0.30 (bulk), 0.44 (tapped) 0.30 (bulk), 0.44 (tapped) Angle of repose (degrees) 41 41 Orifice diameter (mm) 6.3 4.0