(657d) Mechanistic Tablet Breaking Force Prediction from Particle Scale Adhesion Force and Bonding Number

Tablets are widely used in the pharmaceutical industry, yet the current formulation development relies heavily on previous expert knowledge and empirical design of experiments. As a result, there is a need for predictive and computer-based design models that could use mechanistic approaches for faster formulations development based on material properties and smaller number of particle-scale experiments. Existing prediction models are limited in the sense that they require empirical fitting of a model based on powder properties such as particle size, morphology, true density, surface roughness, bonding strength and bonding area, compaction speed and pressure, and tablet porosity. Such models may only work under specific circumstances and do not provide any fundamental insight of particle interactions. Here, we propose a mechanistic model to predict tablet breaking force/tensile strength for single and binary component formulations based on material properties, specifically, bonding strength and bonding number, which is the number of particle bonds per area. This 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. Further, we employ a dimensionless properties averaging approach for prediction of the properties of binary component tablets from those of single-component properties. The proposed model shows good correlation between predicted and experimental results with different active pharmaceutical ingredient (API) powders, compression pressures, and particle sizes. The experiments used to validate the model include 8 single component and 9 binary component formulations. The proposed mechanistic model has the potential to greatly simplify the tablet formulation process for binary and eventually multi-component tablets, only requiring properties assessment for individual/single components. The proposed approach would facilitate faster and more efficient design of tablet formulations for the pharmaceutical industry.

References

1. Eriksson M, Alderborn G. The effect of particle fragmentation and deformation on the interparticulate bond formation process during powder compaction. Pharmaceutical research. 1995;12:1031-9.
2. Sun CC. Decoding Powder Tabletability: Roles of Particle Adhesion and Plasticity. Journal of Adhesion Science and Technology. 2011;25(4-5):483-99.
3. Ryshkewitch E. Compression strength of porous sintered alumina and zirconia: 9th communication to ceramography. Journal of the American Ceramic Society. 1953;36(2):65-8.
4. Wu C-Y, Best SM, Bentham AC, Hancock BC, Bonfield W. A simple predictive model for the tensile strength of binary tablets. European Journal of Pharmaceutical Sciences. 2005;25(2-3):331-6.
5. Sebhatu T, Alderborn G. Relationships between the effective interparticulate contact area and the tensile strength of tablets of amorphous and crystalline lactose of varying particle size. European journal of pharmaceutical sciences. 1999;8(4):235-42.
6. Capece M, Huang Z, To D, Aloia M, Muchira C, Davé RN, et al. Prediction of porosity from particle scale interactions: Surface modification of fine cohesive powders. Powder technology. 2014;254:103-13.
7. Johnson KL, Kendall K, Roberts AD. Surface Energy and the Contact of Elastic Solids. Proceedings of the Royal Society A, Mathematical, physical, and engineering sciences. 1971;324(1558):301-13.
8. Capece M, Silva KR, Sunkara D, Strong J, Gao P. On the relationship of inter-particle cohesiveness and bulk powder behavior: Flowability of pharmaceutical powders. International journal of pharmaceutics. 2016;511(1):178-89.