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34 April 2017 Tablets & Capsules Figure 1 shows the profiles of two formulations, one with poor compaction characteristics and one with acceptable compaction characteristics. The direct-com- pression blend (DB), shows an increase in tablet strength up to 100 megapascals of compaction pressure, after which it loses strength due to capping. The wet-granu- lated blend (WG) shows a continuous increase in tablet strength as compaction pressure increases. If those two blends are to be used in a bi-layer tablet, the DB blend is clearly the better candidate for layer one. In bi-layer tabletting, layer-one compaction involves a tamping force only—consolidating the material and reducing its volume in the die—which leaves room for the second-layer material. The light amount of force also reduces air entrapment and creates more particle- to-particle contact sites that are favorable for bond- ing when the final compression event occurs. The profile in Figure 2 is for a material that is strain-rate sensitive, which means it's affected by turret speed, dwell time, or both. As turret speed increases, the robustness of tablets made from the DB blend suffers, whereas tablets made from the WG blend are insensitive to speed. In this case, too, the DB blend would be better as layer one. Weight measurement Another challenge associated with bi-layer tabletting is controlling and measuring each layer's weight, which pharmaceutical manufacturers typically achieve by sam- pling or separating the layers and measuring them inde- pendently. A high-quality force-instrumentation system designed for bi-layer tabletting can provide real-time mea- surement of each layer's weight. Using that data, you can establish a force-weight profile for each layer's material and set force limits based on acceptable weight tolerances. Look for a force-instrumentation system that accom- modates custom sensors with a high-sensitivity output at the required measured force. A typical 100-kilonewton button load cell for layer one does not fit that criterion because the required tamping force for bi-layer tabletting is typically less than 1 kilonewton, which is less than 1 percent of the button load cell's full-scale loading. With that range, it cannot provide the accuracy and high-sensi- tivity output required. A 10-kilonewton full-scale, roll-pin sensor is a better fit for the application. It can be used to measure the force at each punch station for each layer, identify weight issues for individual layers, and alleviate the need for frequent sampling. Cross-contamination Bi-layer tabletting also poses the challenge of prevent- ing cross-contamination between layers, necessitating proper press setup and an efficient vacuum system. A high-quality tablet press with tight tolerances is also very important. Worn die pockets and excessive turret runouts are common causes of cross-contamination. Even with a high-quality tablet press, cross-contamination can occur from the chamfer where the punch enters the die. Powder can accumulate in the chamfer and contami- nate the other layer. To prevent that, use dies with a radius edge at the die bore instead of a chamfer. This is called a multi-layer lead-in and will eliminate powder accumulation. T&C References 1. Sedlock R. Powder die filling process essential for quality tablets. Natoli Engineering, St. Charles, MO, 2016. Available at www.natoli.com. 2. Sedlock R. Detailed formulation development helps avoid production problems. Natoli Engineering, St. Charles, MO, 2016. Available at www.natoli.com. Robert Sedlock is the director of technical training and devel- opment at Natoli Engineering, 28 Research Park Circle, St. Charles, MO 63304. Tel. 636 926 8900. Website: www.natoli.com. The company manufactures tablet tooling. Figure 1 Compaction profiles 1.4 1.2 1 0.8 0.6 0.4 0.2 0 50 100 125 150 175 200 250 300 Compaction pressure (MPa) Tensile strength (MPa) DB WG Figure 2 Strain-rate-sensitivity profiles 1.4 1.2 1 0.8 0.6 0.4 0.2 0 Tensile strength (MPa) DB WG 39.70 26.47 19.85 15.88 13.23 Dwell time (ms) Establish a force-weight profile for each layer's material and set force limits based on acceptable weight tolerances.