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Tablets & Capsules September 2020 51 and the thickness increased by only 0.09 millimeter, indicating that the co-processed excipient seems to maintain the practical hygroscopic stability of ODTs. decrease in tablet hardness seems suf- ficiently small for practical use. The increase in tablet thickness was also sufficiently small at only 0.07 milli- meter. The results of a stability test at 40°C/75 percent RH are shown in Figures 4a and b. The tablet hard- ness decreased by only 30 percent, are co-processed into nonspheri- cal-shaped particles with a mean par- ticle size of 106 microns. The non- spherical shape is purposely designed to enable better content uniformity in tablet form. A scanning electron microscope (SEM) image of sample particles is shown in Figure 1. Disintegrability and compactability of placebo ODTs To prepare the ODTs, the co-pro- cessed excipient is blended with one or more active pharmaceutical ingre- dients (APIs), flavors, sweeteners, and lubricants and then compressed using a conventional tablet press. Placebo ODTs showed satisfactory rapid disintegration and compacta- bility without the addition of dis- integrants or binders. The disinte- gration time is plotted against tablet hardness in Figure 2a, with the dis- integration time measured both by sensory evaluation (in vivo) and the pharmacopoeia test method (phar- macopoeia). Even at a tablet hardness of around 100 newtons, the ODT tablets maintained a short disintegra- tion time (<20 seconds). Moreover, the co-processed excipient showed excellent compactability. As shown in Figure 2b, the tablet hardness reached around 100 newtons under a compression force of only 5 ki lo new- tons, demonstrating that the excipi- ent might be suitable for application with poorly compressible APIs. Hygroscopic stability of placebo ODTs As a small amount of water is a trigger for the disintegration of ODTs in the oral cavity, it is gen- erally difficult to maintain robust hygroscopic stability in terms of tab- let hardness for ODTs. However, the co-processed excipient provided satisfactory stability in placebo tab- lets. Placebo ODTs were stored open at 25°C/75 percent relative humidity (RH) for 3 months, with the tablet hardness, disintegration time, tablet thickness, and tablet weight evalu- ated at intervals, as shown in Figures 3a and b. Tablet hardness decreased gradually, but the difference was only 25 percent after 3 months. This Figure 3 Stability when stored open at 25°C/75% RH of placebo ODTs containing co-processed excipient (99.0%) and sodium stearyl fumarate (1.0%) (Rotary tablet press, 200 mg, 8 mm diameter, flat beveled-edge shape) a. Tablet hardness and disintegration time versus storage time b. Tablet thickness and tablet weight increase rate versus storage time Tablet hardness (newtons) 140 120 100 80 60 40 20 0 Time 3 months 3 months 2 months 2 months 1 month 1 month 2 weeks 2 weeks 1 week 1 week Initial Initial Disintegration time (seconds) 35 30 25 20 15 10 5 0 Tablet hardness Disintegration time Tablet thickness (millimeters) 3.20 3.15 3.10 3.05 3.00 Time Tablet weight increase rate (%) 2.0 1.5 1.0 0.5 0.0 Tablet thickness Tablet weight increase rate Figure 4 Stability when stored open at 40°C/75% RH of placebo ODTs containing co-processed excipient (99.0%) and sodium stearyl fumarate (1.0%) (Rotary tablet press, 200 mg, 8 mm diameter, flat beveled-edge shape) 2.0 1.5 1.0 0.5 0.0 a. Tablet hardness and disintegration time versus storage time b. Tablet thickness and tablet weight increase rate versus storage time Tablet hardness (newtons) 140 120 100 80 60 40 20 0 Time Time 3 months 3 months 2 months 2 months 1 month 1 month 2 weeks 2 weeks 1 week 1 week Initial Initial Disintegration time (seconds) 35 30 25 20 15 10 5 0 Tablet thickness (millimeters) 3.20 3.15 3.10 3.05 3.00 Tablet weight increase rate (%) Tablet hardness Disintegration time Tablet thickness Tablet weight increase rate