Predicting the compressibility and compactibility profiles of pharmaceutical active ingredients for design of multi-component tablets

June 25, 2026, midnight - by Chuhong Cheng , Ke Wang , Walkiria Schlindwein , Carol Crean , Chuan-Yu Wu , Zhonggui He , Xiaohong Liu , Mingzhong Li

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Digital design of multi-component pharmaceutical tablets based on the properties of their individual constituents is a valuable approach for the rational development and optimization of pharmaceutical formulations. Most active pharmaceutical ingredients (APIs) used in tablet formulations are crystalline materials exhibiting diverse mechanical behaviours, including elastic, plastic, brittle, or combined deformation. These properties can contribute to manufacturing challenges such as capping and sticking or result in mechanically weak tablets, making the direct compaction and characterization of pure APIs difficult or even impractical. This study presents an approach for predicting the compressibility and compactibility profiles of APIs that cannot be directly compacted into tablets without excipients. The proposed method combines the assumption of additive volume fractions with a geometric mean mixing rule applied to the compactibility models of individual components. API compressibility and compactibility models were derived from out-of-die compaction data obtained from binary powder mixtures containing 50% API and 50% microcrystalline cellulose, compressed at different compaction pressures. Five APIs with diverse mechanical properties—aspirin, carbamazepine, metronidazole, paracetamol, and theophylline—were investigated. The proposed approach successfully predicted tablet solid fraction and tensile strength for both binary mixtures containing API and filler and ternary mixtures containing API, filler, and disintegrant. Predicted solid fractions were within ±5% of the measured values, while tensile strength predictions showed errors typically ranging from ±20% to ±50%, depending on the API, formulation, and compaction pressure. Overall, the proposed approach provides a practical digital design tool for predicting the compaction behaviour of multi-component pharmaceutical tablets based on the properties of their individual constituents, supporting more rational formulation development and optimization.

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