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Tablets & Capsules September 2014 11 differences in thickness—as little as a few tenths of a millimeter—can have a dramatic effect on other tablet properties. That's why instead of thickness, it would be more prac- tical to compress a series of tablets at different forces under otherwise similar conditions. By so doing, you could determine how compaction affects the tablet over a mea- sured range of forces or pressures, which would enable you to fully characterize the material being compressed. Full characterization requires measuring three tablet para- meters: compaction pressure, tensile fracture stress, and solid fraction. These three parameters form the "com- paction triangle" shown in Figure 1 [2]. Each should be measured from the earliest stages of formulation and con- tinuously throughout the tablet development process. The importance of an instrumented press Determining tensile fracture stress (sometimes simply called tensile strength) entails measuring the load required to break the tablet under controlled conditions. Knowing the tablet's tensile strength is useful because the value is a linear function of compaction pressure [3] up to a limiting value of pressure. As a result, once a formula- tion has been characterized, compacting a single tablet at a known pressure enables you to determine its compres- sion properties. Likewise, the solid fraction of a tablet increases as compaction pressure increases, although that relationship is not linear. There are many cases cited in the literature of tablets with extremely high solid frac- tions: 0.95 or greater. Compaction under those condi- tions is likely to cause capping or delamination, and water penetration of the tablets will be poor. A solid frac- tion of 0.85 to 0.90 is optimal. Pitt et al. [4] provide additional guidance for optimum performance, including a recommendation that tablets have a minimum strength of 2 megapascals (MPa) when compressed at a compaction pressure of 200 MPa, the maximum pressure that most tablet manufacturing opera- tions recommend. The same study also recommends an ejection stress—calculated from the force needed to eject the tablet from the die—of not more than 5 MPa. As Pitt's study and other recent data demonstrate, tablet development should follow a continuous, iterative process in which the formula and processing variations are systematically evaluated, in some cases using designed experiments, which the FDA has dubbed Quality by Design (QbD). But that's a difficult task for pharmaceutical scientists, most of whom have limited access to sophisti- cated compaction simulators and lack the expertise re - quired to use them. Most of these simulators are found in a manufacturing environment, not the development lab. This lack of access and expertise led us to develop a bench- top laboratory tablet press (photo) [5]. It is a relatively inexpensive and easy-to-use lab-scale and at-line simulator that helps product development scientists and others who seek to optimize the process of making solid-state formula- tions. It also helps control quality and enables you to trou- bleshoot ingredient and batch-to-batch variations that contribute to tablet failures during manufacture. By using a benchtop tablet press, you can specify and control the force applied while the instrument records both the force and the punch position during compaction and ejection. It can display those parameters in real time. Table 1 Causes of capping problems and methods of resolving them, as identified by Wood in 1906 [1]* Cause Solution Imperfect upper punch Replace Imperfect or worn die Replace Imperfect alignment of punches or dies Remedy machine setup Too much pressure Reduce pressure Damp granulation Reduce moisture content Too much fine powder in granulation Remove fines or increase granule size Granulation too soft Granulate to correct endpoint Wrongly proportioned excipients Correct over- or under-granulation. Re-granulate to form proper granules using a better binder. If formulation is too soluble, switch to solvent with lower solubility. * At the time, all products were made by wet granulation. Figure 1 The compaction triangle [2] Compaction pressure Solid fraction Compressibility Tensile strength Compactibility Tabletability Benchtop tablet press and material tester [5]