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how many mini-tablets are filled into a capsule. The compaction analyzer. The powder compaction analyzer used in this study produces tablets 2 to 15 mm in diameter and uses a computer that precisely controls and records both force and punch position in real time. This analyzer was recently upgraded to include a rotating die plate that enables it to automatically measure and record tablet detachment (take-off) force and tablet ejec- tion force. It also allows you to program a pre-set dwell or "hold" time after maximum compression is obtained. The hold time can last 90 milliseconds (ms) to 1 minute. Because the analyzer records both force and punch posi- tion in real time, it can also record in-die dynamic changes in real-time using Heckel and Kawakita parame- ters at all compression forces—not simply the maximum force—while simultaneously tracking real-time changes in tablet volume. This dynamic measurement capability offers a new avenue for exploring and understanding powder compaction. The tensile analyzer. The tensile tablet analyzer used in this study automatically records out-of-die weight, thickness, and diameter of tablets made using the powder compaction analyzer. It then measures the TTFS. The CQAs of an ODMT require that it be measured under controlled compaction pressure. In this case, the CQAs were solid fraction, friability, disintegration, and TTFS. (Dissolution test performance is not a CQA of ODMTs.) Figure 4 Powder compaction analyzer and tablet tensile analyzer used to assess tabletability The methodology for measuring these four CQAs included • Blending the formulation with a lubricant (1 percent magnesium stearate) for 3 minutes using a Turbula mixer (WAB, Muttenz, Switzerland). • Weighing out the resulting mixture and making tablets 3 mm in diameter, each weighing 25 milligrams (mg). The compaction, detachment, and ejection forces were recorded. • Testing friability. • Comparing the disintegration times of the compacts with respect to the different compaction forces. • Characterizing the compacts, which included mea- suring their weight, thickness, diameter, and TTFS. Solid fraction. Measuring the solid fraction is useful for comparing formulations with significantly different com- positions, and for a fair comparison, the formulations should be compared at similar solid fractions. The com- parison requires accurately measuring the true density of the formulation. This is not always available, so in many cases the optimization is based around the use of com- paction pressure measurements, as discussed in this article. The relationship of the TTFS to compaction pressure is fundamental and arises from the characteristics of a for- mulation or material. This relationship has been shown to extrapolate to compaction behavior during production. Thus, based on the results of a simple laboratory test, we can make reliable predictions about production behavior. Figure 5 shows the effect of compaction pressure on the TTFS of the ODMTs. This is generally a linear rela- tionship until high solid fractions are reached and thus provides a simple and objective way to compare tablet formulations and processes. Friability test. Seven ODMTs made at four com- paction pressures (139, 208, 278, and 345 MPa) were tested in a friabilator (Erweka, Heusenstamm, Germany) set for 100 revolutions (25 rpm for 4 minutes). Table 1 and Figure 6 show the results. Achieving friability limits can be difficult when formu- Figure 5 TTFS versus compaction pressure for ODMTs made from a coprocessed excipient 4.00 3.50 3.00 2.50 2.00 1.50 1.00 0.50 0.00 TTFS (MPa) Compaction pressure (MPa) 0.00 100.00 200.00 300.00 400.00 500.00 600.00 700.00 800.00 30 May 2016 Tablets & Capsules