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Tablets & Capsules May 2014 23 Characterizing the individual layers Before jumping into bi-layer tabletting, understand the characteristics of each tablet layer. How do you deter- mine which layer is going to be the first layer and which second? Due to the design of bi-layer tablet presses, it may be better to designate the material requiring a higher fill depth as layer one. But when the material can be formed as either layer, use the material that benefits more from pre-compression as layer one. Pre-compression is essentially a de-aeration stage that consolidates the parti- cles and helps produce a more robust tablet. The graph in Figure 1 shows the results of a compaction profile study of individual layers. Compaction profiles are a very effective tool for developing formulations because they help you understand the physical properties of the materials and tablets when compressed at different force levels. The conventional way of presenting compaction data is to show the relationship be tween the applied com- pression force and the resulting breaking force, which is erroneously but commonly referred to as tablet hardness. This relationship between compression force and breaking force changes, however, as the geometry of the tablet changes. Thus, a more meaningful approach is to convert the applied compression force to compression pressure and convert breaking force to tensile strength. In Figure 1, Material A reaches its maximum com- pactability at 218 megapascals (MPa) of compaction pres- sure, and during breaking force tests, capping was observed in tablets produced at higher pressures. Capping refers to tablet failure on the horizontal plane (not the diametrical aspect). There are many causes of capping, including excessive fines, entrapped air, and too much lubricant. In a repetition of the study that included the addition of a small amount of pre-compression pressure, Material A performed better. Compactability increased and capping was not observed until force exceeded 255 MPa. Material B showed higher compactability and did not benefit from the addition of pre-compression force. In this case, Material A is the clear choice for layer one since it will undergo two compression events, with the layer-one compression rollers providing the pre-compression. Figure 2 shows the results of a strain rate study per- formed on individual layers. The strain rate study helps you understand the compaction properties of materials compressed at different loading rates or dwell times. Tablets made from some excipients and APIs are accept- able (i.e., good mechanical strength) when made on a small R&D press, but fail when made on a high-speed, large-scale manufacturing press. Such materials are said to be strain-rate sensitive. Studying strain rate is helpful because it can indicate the potential for problems when you scale up to a commercial press. In the graph in Figure 2, the bottom axis is normalized for the turret's pitch circle diameter, which allows you to compare data from studies that used different turret sizes. The left axis is the tablet strength, and the results have been normalized for any weight loss stemming from shorter feeder dwell times. The red trace represents a material that is strain-rate sensitive. This material is characterized as a plastic or ductile-dominant material. The material represented by green trace does not show significant adverse effects and can be characterized as a material in which brittle fracture dominates. In this case, the plastic material would per- form better as the first layer because it would benefit from pre-compression. Most modern bi-layer tablet presses have compression rollers of equal diameter but in the past most used a smaller roller for layer one (pre-compression). Today's larger rollers increase the loading rate and can help make good tablets from a strain-rate sensitive material because they allow more time for the material's particles to con- solidate and for interstitial air to be tamped out. Proper setup maximizes yield The fill cam is one variable among many that influence product yield and it is often overlooked. Located under the lead section of the feeder, the fill cam pulls the lower punch down to enable the feeder to deliver powder into the die. The size of the fill cam (photo) indicates the maximum Figure 1 Compaction profile study of individual layers: compression force vs. tensile strength 2,000 1,900 1,800 1,700 1,600 1,500 1,400 1,300 1,200 1,100 1,000 900 800 700 600 500 400 300 200 A A (Pre) B B (Pre) 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 Compression force (MPa) Figure 2 Strain rate study of individual layers 8 7 6 5 4 3 2 A B 150 200 250 300 350 400 450 500 550 600 Tangential velocity (mm/sec) Breaking force/compression force ( 1 ⁄1000) Tensile strength (MPa) g-Sedlockart_22-27_Masters 5/14/14 10:16 AM Page 23