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eye on Defining the critical quality attrib- utes (CQAs) of tablets or capsules is integral to QbD, and identifying the elements that could put CQAs at high risk is part of the QbD design space. Historically, blending and compression rank among the high- risk operations. To assess risk and devise ways to mitigate it require a thorough examination of these oper- ations and their effects on the pro - cess and final product. That is the only way to acquire the data needed to determine whether tabletting or capsule filling has a negative effect on the CQAs. If it doesn't, we can consider the formulation robust. While risk assessment in QbD merits an article unto itself, here we are simply defining it as a measure of the likelihood that a process will yield excessive CQA deviation, with an eye on what we know about the variables in the process and what control measures are in place. Effect of lubricants Magnesium stearate (MgSt), a ubiq- uitous tablet lubricant, diminishes tablet hardness when used with MCC. Its effects vary with the amount of lubricant used and the duration of blending [1]. Studies show that blends of MCC and MgSt exhibit greater lubricant sensitivity and are more sensitive to tablet press speed than blends of sili- cified microcrystalline cellulose (SMCC) and MgSt [2]. On the other hand, compared to MgSt, sodium stearyl fumarate (SSF), another popu- lar lubricant, produces minimal nega- tive effects with respect to amount and blend time when blended with MCC [3]. Studies of SSF-SMCC and MgSt-SMCC blends show that the SSF-SMCC combinations form supe- rior capsule plugs [4]. Studies by Muzíková demonstrate that this effect holds true when various lubricants are combined with SMCC in placebo tablets [5]. In short, using HFEs such as SMCC in combination with SSF can reduce risk and dramatically sim- plify the design of experiments during formulation development. Surprisingly, there are few studies available like the one detailed in this article, which incorporate a model API into the evaluation of how lubricants (MgSt and SSF) and binders (MCC and SMCC) affect one another with respect to excipient amount and blend time (Table 1). The data from this study indicate that using quality materials such as HFEs prevents prob- lems and simplifies risk-mitigation studies, leading to superior dosage forms with less development time required. The placebo data suggest general trends, and the model API for- mulation with chlorpheniramine maleate (CPM) reinforces the patterns identified in the placebo models. The results of tests on the SMCC placebo formulation (Figure 1) illus- trate the effects of lubricant amount and blend time on tablet hardness. Tablets & Capsules May 2015 33 David Schaible and Louis Mejias JRS Pharma excipients Lubricants can have a negative impact on tablet hardness and other critical quality attributes. In this edition, our guest columnists discuss the results of a study that compared how blends made using silicified microcrystalline cellulose and microcrystalline cellulose and two differ- ent lubricants performed on a tablet press. In decades of troubleshooting for- mulations for customers, some of the most common issues we've encoun- tered involve lubricant sensitivity of microcrystalline cellulose (MCC) and, to a lesser extent, other excipi- ents. Lubricants often cause problems during development, scale-up, and production. In many cases, these problems could have been avoided by using high-functionality excipi- ents (HFEs). These may be defined as excipients which: serve more than one function (e.g., both binder and glidant or binder and disintegrant); have inherently high functional per- formance allowing larger batch sizes and/or higher drug loading even at relatively low usage levels; require no complex processing; and, impart their desirable performance characteristics to the overall formulation. Likewise, a more comprehensive understanding of the tablet-making process—as the FDA's Quality-by-Design (QbD) ini- tiative is intended to foster—would also have helped avoid formulation performance problems.