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C 24 July 2017 Tablets & Capsules excipients A novel MCC for reducing segregation in direct-to-press blends Yosuke Honda and Syozo Kaneyama Asahi Kasei Stephen Turner Asahi Kasei America This article describes a novel MCC and presents a study in which it is shown to decrease segregation in a low-dose tablet compared to a tablet made using an industry-standard MCC. ontent uniformity of the active pharmaceutical ingre- dient (API) in tablets is critical because it ensures patients receive the same dose from tablet to tablet. But it becomes increasingly difficult to attain content unifor- mity as the API dose decreases because the API segre- gates more readily from the formulation's excipients. Wet and dry granulation limit segregation, but both techniques add time and cost to tablet manufacturing. Manufacturers would prefer to simply blend the ingredi- ents and send them to the tablet press. Such formulations are known as direct-to-press blends, and the process is called direct compression. This article describes a novel microcrystalline cellulose (MCC) that limits segregation of APIs in low-dose tablets, allowing formulators to more easily create direct-to-press blends [1]. It also presents the results of a study that show that the novel MCC pro- vided better content uniformity than an industry- standard MCC in tablets containing a low-dose API. Compactability and flowability Manufacturing a tablet by direct compression requires taking many factors into consideration, including the par- ticle size, shape, flow, and compressibility of the materi- als and how those properties affect content uniformity. The process itself must also be evaluated because segre- gation can often occur during blending and/or in the hopper and feed system of the tablet press. Figure 1 illustrates the tradeoff between compactabil- ity and flowability in all MCCs. The novel MCC dis- cussed here maintains a standard degree of compactabil- ity while improving flowability (repose angle of 34 degrees), which minimizes segregation during blending and enables manufacturers to gravity-feed blends during direct compression. Particle properties The compactability index was calculated using tablet hardness data from each MCC grade based on a common tablet formulation. The hardness of tablets containing PH-101 was set at 100. Each tablet comprised 70 percent acetaminophen and 30 percent MCC and was com- pressed to a target tablet weight of 500 milligrams on a static tablet press at 7 kilonewtons in a 11.3-millimeter- diameter die by a flat-faced punch. The flowability of each MCC was quantified based on its repose angle. See Figure 1. Table 1 lists some common tablet properties. The bulk density of the novel MCC is nearly equivalent to that of the PH-101 and shows the best repose angle of the MCCs tested. The micrograph in Figure 2 shows that the novel MCC comprises predominately round, aggregated particles. This particle shape greatly contributes to the novel MCC's superior flow. A cross-sectional view of the particle reveals its porosity (Figure 3). This porous struc- ture improves the MCC's plastic deformation, which allows it to provide good compactablity during direct compression. Figure 1 Compactability versus flowability of MCC Flowability (repose angle) Compactability index 250 200 150 100 50 0 58 53 48 43 38 33 KG-1000 KG-802 PH-101 PH-102 PH-302 PH-301 PH-200 Novel MCC [1]