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Tablets & Capsules May 2016 29 • Compactibility: The ability to yield a compact of adequate deformation resistance when compressed. • Tabletability: Tablet tensile strength as a function of compaction pressure. To better understand powder compaction, we've undertaken a dynamic in-die analysis of both the com- pression event and the tablet dimensions. That enables us to record in real time how a tablet's solid fraction changes as a function of compaction pressure. Next, by combin- ing this information with fracture-stress data from the resulting tablet, we can accurately predict which of the formulation's specific properties needs to change in order to create an optimal tablet. This data also enable us to generate a full profile of the compressibility, compactibil- ity, and tabletability of a single sample. Furthermore, by entering this information—specific to both excipients and APIs—into a database, formulators can streamline their future efforts and be more prepared to undertake Quality-by-Design (QbD) initiatives. It's even conceivable that an at-line QC operation could use such a database to gain insight into the compression properties of in-process materials via a single-point mea- surement [3]. An example of how to collect and apply compaction data is discussed below. But first, let's review the principal component of the compaction triangle: tabletability. A brief review of tabletability Based on the work of Newton and Fell [4], tabletabil- ity is defined as the relationship between compaction pressure and tensile strength. In his pioneering paper of 1972 [5], Newton calculated tablet tensile fracture stress (TTFS) values using this formula: where t is the TTFS expressed in megapascals (MPa) P is the breaking load expressed in newtons (N) D is the tablet diameter expressed in millimeters (mm), and t is the tablet thickness expressed in mm. In practice, the TTFS is easy to measure. Simply apply a diametral load very slowly to a flat-faced tablet and measure the force required to break it (Figure 3). As long as your instrument is sufficiently sensitive, this technique can differentiate easily between small differences in TTFS. As you would expect, the formulation and/or process with the best tabletability—the material that results in the strongest tablet at a given pressure—is usually the best. That's because the tablet can be made at the lowest compaction pressure, which makes it easier to manufac- ture. This tablet would also have the lowest solid fraction (highest porosity) of the formulations studied, which typ- ically corresponds to the best dissolution behavior. In fact, measuring tabletability is recognized as a simple, highly sensitive, and effective way to characterize and t = 2P Dt compare the compaction properties of component mate- rials and powder formulations. Plus, the measurements are independent of both tablet size and shape. Because tabletability accounts for the effects of the formulation and the process, it offers formulators a practical and valu- able approach [3]. Assessing the compaction behavior of orally dispersible mini-tablets There are several good reasons for improving how we assess individual materials before defining the com- paction design space of a formulation. The best reason: It would minimize trial and error—thus saving valuable development time—by applying knowledge-based prin- ciples instead of relying on empirical observations and experience. This is particularly valuable when character- izing excipients, which are subject to batch-to-batch vari- ation. Many excipient variations are supplier-dependent and may be difficult or impossible to predict or control. Thus, implementing a protocol to evaluate the com- paction properties of incoming excipients can help you screen new batches before you incorporate them into a new tablet formulation. To illustrate how such tests can improve our assess- ment of tablets, we studied the effect of compaction pres- sure on the CQAs of orally dispersible mini-tablets (ODMTs). The study used a PCA-500 powder com- paction analyzer (Gamlen Tableting, Nottingham, UK) and a TTA tablet tensile analyzer (Gamlen Tableting). See Figure 4. The ODMTs were prepared using SmartEx (Shin Etsu, Tokyo, Japan), a coprocessed excipient that comprises low-substituted hydroxyproyl cellulose as the disintegrant, mannitol as the filler, and polyvinyl acetate as the binder. ODMTs are designed to disintegrate with- out water inside the buccal cavity. They are particularly useful for dosing pediatric and geriatric patients who have difficulty swallowing. The dissolution profile of an API delivered via ODMTs is easy to control by varying Figure 3 Diametral measurement of TTFS