(26h) Expanding the Mechanical Property Assessment of Pharmaceutical Tablet Dosage Forms to De-Risk Manufacturing

Following pharmaceutical tablet compression, physical forces from de-dusting, coating, and packaging can adversely affect tablet integrity, potentially introducing defects such as chipping, erosion, and fracturing that may result in broken tablets. For these reasons, the physical strength of compacted powder is critical to ensuring the quality of pharmaceutical tablets. Thus, its measurements help assess the friability of tablet formulations and the corresponding risk associated with each step of the tablet manufacturing process.

In pharmaceutical manufacturing, the strength of a tablet is most often quantified through its breaking force per USP <1217>. The method outline therein involves producing a tablet using a standard punch and die, placing the tablet between two parallel platens, and compressing the tablet with the platens until it breaks. The force observed at the point of breaking is then taken as the tablet breaking force. In this presentation, we expand upon the generally accepted means for assessing the strength of compacted pharmaceutical powders.

The first part of the presentation explores different methods of producing a tablet and its impact on the tablet strength. Here, we consider two different means of achieving tablet relaxation when it remains in the die following the maximum densification: uni-axial and tri-axial decompression. Taking the ratio of the strength of the tablet made under uni-axial decompression to that made under tri-axial decompression allows assessment of the material sensitivity to the unloading and ejection process during a standard compaction process.

The second part outlines different methods for assessing the quasi-static failure of compacted powder. Herein, we present the effects of anisotropy measured by the ratio between a compact’s shear strength and its tensile strength. In the case of inherently anisotropic materials whose shear strength is demonstrably lower than its tensile strength, we pose that the former quantity is a better indicator of strength for risk-assessment purposes. In addition, we also evaluate the tensile strength ratio of the tri-axially decompressed compacts made with and without a small pinhole (i.e. the brittle fracture index) to assess the effects of sensitivity to stress concentration on the tablet’s propensity to ejection-related defects (e.g. capping, lamination, etc.).

For both parts, we present the values for commonly used pharmaceutical excipients and show that significant deviations from these values result in tablet defects generally associated with the ejection process. Additionally, from our collection of experimental trends, we propose a regime map constructed using the three different ratios outlined above and demonstrate how this map may be used for assessing the risks of a tableting process.