Issue link: https://www.e-digitaleditions.com/i/1371139
28 May/June 2021 Tablets & Capsules Tabletability As set out in USP <1062>, a tabletability profile describes how tablet tensile fracture strength (TFS) changes with compaction pressure. Tablet tensile frac- ture stress is calculated from the tablet breaking strength, often referred to as tablet hardness, accounting for the dimensions of the tablet. Tablet tensile fracture stress = 2 (Breaking stength) π (Diameter) (Thickness) TFS is often the most discriminating and useful piece of data generated by compaction analysis. The higher the TFS, the better the product is able to withstand handling and processing. The recommended minimum TFS is 2 megapascals at compaction pressure of 200 megapascals. The example tabletability profile in Figure 2a shows significant differences in tablet strength between the three formulations, with F2>F1>F3. The F3 tablets are the weakest by far, with tablet tensile fracture stress val- ues falling in the "poor" region of the plot. If selected for use, this formulation can be expected to generate major production issues associated with low tablet hardness. The data for the other two formulations fall within the borderline region and do not achieve the recommended strength values. These formulations can also be expected to lead to compaction problems, including high friability and erosion during film coating. Compressibility A compressibility profile shows how the solid fraction of the tablets changes with increasing compaction pres- sure. The solid fraction of a tablet is the inverse of its porosity. A tablet with a high solid fraction will have a low porosity. For example, a tablet with a solid fraction of 0.9 has a porosity of 0.1. Solid fraction is calculated as: Solid fraction = Tablet density Material true density A tablet's maximum recommended solid fraction depends on the properties of its principal component. For most materials, a maximum solid fraction of 0.95 is recom- mended, but some materials (notably calcium salts) require higher values to achieve acceptable tablet properties. High solid fraction values are linked to capping issues in production and can also result in long dissolution times, as the low porosity prevents liquid from penetrating into the tablet. In the example compressibility profile shown in Fig- ure 2b, the solid fraction values for all formulations across all compaction pressures are between 80 and 95 percent. However, as the compaction force increases, Formulation 3 shows very little change in density. This is a warning sign of possible problems. A good formulation shows a progressive increase in density with increasing com- paction pressure. Formulations that have plateaued at a particular density are prone to capping, as the limits of tion measurements and tablet elastic recovery. A set of example data for three formulations is provided for illus- trative purposes. The data was generated using a Gamlen compaction analyzer. Fifteen tablets were manufactured from each formulation using five different compaction pressures (three tablets at each pressure). The tablets were then weighed, and their dimensions measured before their breaking strength was measured using a Gamlen Tablet Tensile Analyser. Figure 2 Example USP <1062> compaction data comparing three formulations Formula 1 Formula 2 Formula 3 Good Borderline Poor a. Tabletability profile Tablet tensile fracture stress (megapascals) 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 Compaction pressure (megapascals) 0 50 100 150 200 250 b. Compressibility profile Solid fraction 0.95 0.90 0.85 0.80 0.75 0.70 0.65 0.60 Compaction pressure (megapascals) 0 50 100 150 200 250 c. Compactibility profile Tablet tensile fracture stress (megapascals) 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 Solid fraction 0.80 0.94 0.92 0.90 0.88 0.86 0.84 0.82