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48 April 2016 Tablets & Capsules ent use levels in formulations that included three different active phar- maceutical ingredients (APIs): aceta- minophen (APAP), ibuprofen, and acetylsalicylic acid (aspirin). The results presented in Figure 1 show that as the use level of M-5P fumed silica increased, the flowability of all three powder formulations improved, going from "cohesive" to "passable flow" to "free flowing." Note: For highly hygroscopic materials or for materials that exhibit poor flow due to static charge, the amount of fumed silica required may increase by three to four times over what would other- wise be needed. Die filling One requirement of manufactur- ing uniform tablets is getting the powder into the dies in a repro- ducible manner. For that to occur, the powder must flow reliably and not clump, bridge, or build up a sta- tic charge. Adding fumed silica to a powder formulation makes it flow better. It also allows particles to rearrange within the die during die filling and in the early stages of com- pression. Figure 2 illustrates that the average weight of APAP tablets cor- relates positively to the use levels of M-5P fumed silica in the formulation and the length of mixing time. (More consistent tablet weights indicate an improvement in die filling.) The addition of fumed silica has also been shown to help tablet manu- facturers produce high-quality tablets of uniform weight at higher tablet press speeds than would be possible without fumed silica. This improves productivity and throughput. As Figure 3 shows, without the addition of fumed silica, the average weight of ibuprofen tablets decreased by 11 percent when made at high produc- tion speeds. This indicates that the powder had difficulty filling the die cavity. In contrast, tablets made from a powder that included 0.25 percent M-5P fumed silica exhibited more consistent weights at high press speeds. Indeed, when ibuprofen tablets are made at high speed, the addition of fumed silica to the formu- lation has been shown to reduce tablet weight variation by 30 to 40 percent compared to the same for- mulation without it. Furthermore, the addition of fumed silica has been shown to decrease the coefficient of variation of API content in a tablet batch. Tests showed that tablets made from a powder containing 0.5 percent of M-5P fumed silica—when mixed for 1, 5, and 15 minutes—had little vari- ation in API content. Tablets made from the same powder mixed for 15 minutes—but without the addition fumed silica—had a coefficient of variation of 6 percent. That is 12 times higher than the variation Figure 2 Effect of M-5P fumed silica on tablet weight at different use levels and mixing times 410 390 370 350 330 310 290 270 250 0.1 0.25 0.5 1 minute 5 minutes 15 minutes Average tablet weight (mg) / n=10 Note: Formulation includes 10 percent APAP and balance is lactose. Bars correspond to minimum and maximum tablet weight. Figure 3 Effect of M-5P fumed silica and press speed on tablet weight 0.34 0.33 0.32 0.31 0.3 0.29 0.28 Press speed (rpm): 11% decline in average tablet weight No glidant M-5P fumed silica 40 20 60 Average tablet weught (g) Note: Ibuprofen tablets with 0.25 percent fumed silica Usage level of M-5P fumed silica (weight %)