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make the target- and high-hardness tablets increased. The DTs of target-hardness tablets compressed using the blend from low, target, and high roll pressures were 4:00, 4:57, and 6:13 (minutes:seconds), respectively. Also, the DTs of the high-hardness tablets compressed using the blend from low, target and high roll pressures were 5:33, 7:59, and 8:26, respectively. Overall, the roll pressure had a significant effect on the DT of the target- and high- hardness tablets, even though the hardness values were equal. These results suggest that it is important to opti- mize the roll pressure during product development and to control the roll pressure during product manufacture. The friability of the tablets from all groups was acceptable (0.2 percent or less). Dissolution profiles. Figures 1 to 3 illustrate the ef fect of roll pressure on the dissolution of indomethacin tablets compressed at low, target, and high hardness. The disso- lution profile of tablets compressed with a blend made using low roll pressure was faster at all three hardness lev- els. At the target hardness, the dissolution profile of tablets compressed with a blend made using low roll pres- sure was significantly higher than those made at the tar- get roll pressure (similarity factor, or f2, of 48) and the high roll pressure (f2 of 45). This may be due to the fact that the target- and high-hardness tablets required more force when compressed from blends made at the target and high roll pressures, possibly because of work harden- ing. At the target and high roll pressures, the solid fraction of the ribbons was found to be higher (Table 3). Fur ther - more, the higher tablet compression force used on the blend made at the target and high roll pressures might have decreased the porosity of the tablets; tablets contain- ing poorly soluble APIs such as indomethacin have slower dissolution profiles when tablet porosity is low. In general, the dissolution profiles of the tablets com- pressed with blends made at the target and high roll pres- sures were similar for all three hardness levels. This might be because the final blends had equal bulk densities when the target and high roll pressures were used. The dissolution at 5 minutes was significantly greater for tablets compressed from the blend made at low roll pressure. These results demonstrate that roll pressure has a significant effect on the dissolution of indomethacin tablets, even though the tablet hardnesses are equal. It should be noted that the force required to produce a particular tablet hardness was less for the blend made at low roll pressure than it was for blends made with the target and high roll pressure. The differences in the dissolution values at the earlier time points might indi- cate significant differences in the bioavailability of tablets containing poorly soluble APIs, such as indomethacin. These results suggest that roll pressure is a critical process parameter for tablets containing poorly soluble APIs and it needs to be optimized during product development and used as an in-process control during product manufacture. Figures 4 to 6 illustrate the effect of tablet hardness on the dissolution profile of tablets made from blends at the low, target, and high roll pressure. The dissolution of the high-hardness tablets showed the least dissolution at 5 minutes compared to the target- and low-hardness tablets. In general, the standard deviations of dissolution results for the tablets made from blends using high roll pressure were higher than those made with blends using low and 16 March 2014 Tablets & Capsules Figure 1 Effect of roll pressure on dissolution of tablets compressed at low hardness (7 kp) Minutes % indomethacin release 100 95 90 85 80 75 70 65 60 5 10 20 30 45 60 75 Low pressure (2 MPa), low hardness (7 kp) Target pressure (3.5 MPa), low hardness (7 kp) High pressure ( 5 MPa), low hardness (7 kp) Figure 2 Effect of roll pressure on dissolution of tablets compressed at target hardness (10 kp) Minutes % indomethacin release 105 95 85 75 65 55 45 5 10 20 30 45 60 75 Low pressure (2 MPa), target hardness (10 kp) Target pressure (3.5 MPa), target hardness (10 kp) High pressure ( 5 MPa), target hardness (10 kp) Figure 3 Effect of roll pressure on dissolution of tablets compressed at high hardness (13 kp) Minutes % indomethacin release 105 95 85 75 65 55 45 35 5 10 20 30 45 60 75 Low pressure (2 MPa), high hardness (13 kp) Target pressure (3.5 MPa), high hardness (13 kp) High pressure ( 5 MPa), high hardness (13 kp) c-Roblesart_8-17 copy_Masters 3/5/14 10:04 AM Page 16