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paction is that it pre-compresses the material, reducing the compressibility of the formulation to be tabletted. The process also requires suitable dry powder flow, so direct-compression-grade excipients are often necessary. Direct compression is the ideal continuous processing option because it eliminates all granulation steps, further simplifying manufacturing (Figure 1). Moreover, in in - stances where die fill is critical—such as in the manufac- ture of multi-layer tablets or mini-tablets—a small quan- tity of the formulation must be precisely and reproducibly metered into the tabletting die. Filling powder into dies that contain pre-compressed tablet layers or that are very small can become inconsistent when the powder contains agglomerates of varying size. These agglomerates vary the volume of voids from one die fill to another, and that vari- ation in void volume leads to greater tablet-to-tablet weight variability. In such cases, it would be advantageous to use a powder blend instead of granules, but directly compressing a powder blend raises concerns about poor flow and segregation of the blend's components during processing. The latter is of particular concern with low- dose APIs because even minor segregation could result in major fluctuations of API content from tablet to tablet. A direct-compression grade of pharmacopeial HPMC 2208 has recently been developed [7]. Like the incum- bent HPMC, this new material is pure HPMC but has a different particle morphology that renders it more flow- able and amenable to roller compaction and direct com- pression. One objective of the study described here was to demonstrate the differences in the powder flow char- acteristics of two HPMCs—the new METHOCEL DC2 and the incumbent METHOCEL CR [8]. Another objective was to gauge how differences in pow- der flow of the two HPMC grades affected the processabil- ity of the powder blends and the properties of the resulting matrix tablets, including their weight and content unifor- mity. Direct-compression trials employing Methocel DC2 and Methocel CR were conducted using a model formula- tion containing metformin HCl. This high-dose, highly sol- uble API constituted half the tablet formulation, with a tar- get API dose of 500 milligrams (mg) per tablet. Comparison of physical properties Both HPMCs are pure, pharmacopeial-grade HPMC 2208. As shown in Figure 2, Methocel CR consists of thin, flattened, and elongated fibrous particles, while Methocel Tablets & Capsules October 2014 15 Figure 1 Process flow diagrams comparing wet granulation, dry granulation, and direct compression Wet granulation Dry granulation Direct compression Measure materials Measure materials Measure materials Mix additional ingredients Mix additional ingredients Mix additional ingredients Compress tablets Compress tablets Compress tablets Dedust and package Dedust and package Dedust and package Wet- mass Wet- screen Dry- screen Roll-compact Mill ribbons Screen Screen Screen Blend Blend Blend Dry Figure 2 Comparison of particle morphologies a. Methocel DC2 a. Methocel CR