Issue link: https://www.e-digitaleditions.com/i/648486
that they disintegrated in 20 to 30 seconds, about the same time required for ODTs made using Granfiller-D. However, when compressed to a higher hardness range, only tablets made using Granfiller-D retained their short disintegration times. This supe- rior hardness-disintegration property enables formulators to incorporate a wider variety of APIs into ODTs (Figure 2). The way that our company's excipi- ent disintegrates also differs from that of many ODT excipients. As ODTs that use conventional excipients disin- tegrate, they divide into block-like pieces. But when ODTs made using Granfiller-D disintegrate, they exhibit a cream-like consistency, which improves mouth-feel (photos). The following sections illustrate some of the excipient's important attributes. Examples of attributes High dose capacity. Even if an API accounts for 30 to 70 percent of a tablet's weight, trial ODTs made with Granfiller-D exhibited satisfactory hardness (greater than 40 to 50 new- tons) and rapid disintegration (less than 20 to 30 seconds). This result suggests that the excipient's particles function as the water-intake route regardless of tablet porosity and the amount of API. Even when the ODTs contained poorly water soluble APIs (e.g., ethenzamide and acetamino- phen) they exhibited excellent hard- ness-disintegration properties at doses of 50 to 70 percent (Figure 3). Disintegration time. For this test, Granfiller-D GNF-D211 and 6 to 18 milligrams of a model API were tablet- ted into 60-milligram, 6-millimeter- diameter ODTs with a hardness of 20 to 30 newtons. Oral disintegration time was 4 to 6 seconds and friability was less than 0.3 percent. No chipping or cracking was observed when the ODTs were removed from a press- through blister (Figure 4). Stress-strain. Many ODTs made using conventional excipients show a clear fracture point when compression force is applied in the radial direction. ODTs made using Granfiller-D, how- ever, show gradual distortion just before reaching the fracture point (Figure 5). They also exhibit a restora- tive force, meaning that the distortion is reversible before the fracture point is reached. These stress-strain character- istics may reduce the occurrence of breakage and chipping of ODTs, even when they are manufactured at low compression force. Stability outside the package. To 38 March 2016 Tablets & Capsules Figure 1 Hardness, disintegration time, and friability of placebo ODTs 40 60 80 100 120 Tablet harndess (N) GNF-D211 GNF-D215 Tablet harndess (N) Friability (%) 0.6 0.4 0.2 0.0 0.6 0.4 0.2 0.0 30 20 10 0 30 20 10 0 Friability (%) Disintegration time (pharmacopoeia) Oral disintegration time (in vivo) Oral disintegration time (in vitro) Friability 40 60 80 100 120 Note: Flat, 8-millimeter-diameter tablets of 250 milligrams made on a rotary tablet press from blend of Granfiller-D (99.5 percent) and magnesium stearate (0.5 percent). Disintegration time (s) Disintegration time (s) As the ODT disintegrates, it exhibits a cream-like consistency. Figure 2 Comparison of disintegration times of high-hardness ODTs 40 60 80 100 120 140 Tablet harndess (N) 50 40 30 20 10 0 Note: Flat, 8-millimeter-diameter tablets of 250 milligrams made on a rotary tablet press from blend of ODT excipient (99.5 percent) and magnesium stearate (0.5 percent). Disintegration time (s) ODT Excipient B ODT Excipient A ODT Excipient C Granfiller-D