(303l) On the Relationship of Interparticle Force and Bonding Number: Predicting Breaking Force of Pharmaceutical Powders and Blends

Tablets are a widely used pharmaceutical dosage form, but their formulation development is heavily reliant on empirical design of experiments and previous expert knowledge. This creates a need for predictive and mechanistic computer-based design models that could enable faster formulation development based on material properties and fewer particle-scale experiments. However, existing prediction models have limitations in terms of empirical fitting of models based on powder properties, which may not provide fundamental insights into particle interactions. To address this, we propose a mechanistic model that predicts tablet breaking force/tensile strength for single and binary component formulations based on bonding strength and bonding number, which is the number of particle bonds per area. This model allows for simplified estimation of rearrangement and fragmentation. To estimate the bonding number, we derive an estimation from JKR model and adopt our previously proposed adhesion force model into bonding force estimation. We further use a dimensionless properties averaging approach for predicting the properties of binary component tablets from those of single-component properties. The proposed model shows good correlation with experimental results for different active pharmaceutical ingredient powders, compression pressures, and particle sizes. The experiments used to validate the model include eight single-component and nine binary-component formulations. Our mechanistic model has the potential to simplify the tablet formulation process for binary and multi-component tablets, requiring only properties assessment for individual/single components. This approach could enable faster and more efficient design of tablet formulations in the pharmaceutical industry.

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