(W0930-06-34) Explaining Deviant Behaviors in the Tabletability of Mixtures

Purpose: Tabletability represents the relationship between tensile strength and compaction pressure. A tabletability classification system has been proposed previously to distinguish different tabletability behaviors of binary mixtures. In this system, “ideal” or type A behavior is associated with a linear relationship between tensile strength and mixture composition. Type B behavior involves a negative deviation from ideality, and type C involves positive deviations [1,2]. At present, the reasons underlying these behaviors have not been described. The objective of this study was to elucidate why different mixtures fall into different classes.

Methods: Six Common tableting excipients were compressed on a Presster (Natoli, MO – formerly MCC, NJ) emulating a HATA 38 station rotary press at compression speed of 20 rpm. Binary combinations of the same excipients were blended at different compositions and compressed under the same conditions. The compacts were stored at ambient temperature over a saturated MgCl₂.H₂0 solution (32-33% RH), and the final dimensions of the tablet were used to calculate the final solid fraction produced at each compaction pressure. The tensile strengths of dimensionally relaxed tablets were determined by a diametral compression test (Instron, MA). Tensile strength was plotted against volume fraction to classify the behavior of each combination, and the behaviors were compared to the properties of the individual excipients in each mixture.

Results: The tabletability classification system compares the strengths of compacts with different compositions when they are formed under the same compaction pressure [1,2]. Figure 1 shows strength-composition plots for 3 different mixtures characteristic of each tabletability class. CombiLac-Emcompress mixtures at 100 MPa exemplify type A behavior (Fig. 1a). This behavior was observed when the components displayed similar compressibilities (∆SF ≤ 0.06) and similar strengths (∆Tensile strength ≤ 0.8 MPa) at a given pressure in our data. This behavior was not common in the materials studied. The vast majority of mixtures displayed negative deviations with profiles that favored the weaker components. Avicel-Lactose mixtures (Fig. 1b) and CombiLac-Emcompress mixtures at 150 and 200 MPa (Fig. 1a) exemplify this behavior. The negative deviations were observed when the individual components showed similar compressibilities (∆SF ≤ 0.06) but different strengths (∆Tensile strength ≥ 0.8 MPa) at a given pressure. The largest deviations were observed in mixtures where the individual components showed the largest differences in strength. Figure 2 shows that the negative deviation increases in magnitude as the strength difference between the individual components increases. A single example of positive deviation was observed in a binary mixture composed of components with different compressibilities and compactibilities. Specifically, this behavior was observed when more compressible HPC was combined with stronger Avicel PH102 (Fig. 1c). It was observed that this behavior, and all the tabletability behaviors, in fact, could be predicted from the individual component’s properties if the differences in compressibility were taken into consideration. Figure 3 shows compactibility plots for each behavior type with the points from each tabletability profile highlighted with different colors. The tensile strengths of each mixture at a given compaction pressure can be explained using the differences in the solid fraction that occur when mixtures with different compositions are compressed to the same pressure. For example, when compressed at 50 MPa, Avicel PH102 has a final solid fraction much lower than the mixture that incorporates just 25 % HPC (DSF >0.10). Even though HPC is the weaker component, the increased density it creates in the mixtures allows the mixtures to have higher tensile strengths than either component at that same pressure.

Conclusion: The relationship between tensile strength, compaction pressure, solid fraction, and mixture composition is critical to the tablet formulation. So-called ideal behavior is observed when components have similar compressibilities and strength at a given pressure. Negative deviations are expected when compressibilities of the components aren’t dramatically different, with larger deviations expected as the differences in individual component strength increases at a given pressure. A combination of components with drastically different compressibilities and compactibilities gives a positive deviation in tabletability that can be completely accounted for by considering the different solid fractions that are produced by the compaction pressure used. Despite being labeled as ideal or deviant, all three tabletability classification behaviors directly reflect the compressibility and compactibility profiles of the components.

References: 1. Fell J.T., ’Compaction Properties of Binary Mixtures’, In Alderborn, G. and Nystrom, C., 1996. Pharmaceutical Powder Compaction Technology. Marcel Dekker, Inc., pp. 501-515.
2. Sun, C.C., 2016. A classification system for tableting behaviors of binary powder mixtures. Asian J. Pharm. Sci., 11(4),
pp.486-491.
3. Duckworth, W., 1953. Discussion of Ryshkewitch paper by Winston Duckworth. J. Am. Ceram. Soc., 36, p.68.


Figure 1. The observed tabletability behaviors for binary mixtures. The tensile strength points at specific pressures were obtained by interpolation between values measured at other pressures. The dotted colored line represents the ideal behavior at the corresponding pressure.


Figure 2. Magnitude of negative deviation from ideality at 50 % compositions displayed by type A and B combinations as a function of strength difference at 150 MPa.


Figure 3. Compactibility overlays for binary mixtures: a) CombiLac – Emcompress, b) Avicel – Lactose 316, and c) Avicel-HPC. The profiles shown are Ryshkewitch-Duckworth fit to tensile strength & solid fraction data. The squares represent the solid fraction at corresponding compaction pressure.