(51d) Quantification of Lubrication and Particle Size Distribution Effects on Tensile Strength and Stiffness of Tablets

We adopt a Quality by Design paradigm to better control the mechanical strength of tablets as a critical quality attribute by understanding the effects of critical process parameters and critical material attributes. To this end, the effect of particle size distribution, lubricant concentration, and mixing time on the tensile strength and stiffness of tablets were studied.

Two grades of lactose, lactose α-monohydrate and spray-dried lactose, were selected. Tablets were compressed to different relative densities ranging from 0.8 to 0.94 using an instrumented compactor simulator. We propose a general model, which predicts the elastic modulus and tensile strength envelope that a specific powder can obtain based on its lubrication sensitivity for different particle size distributions. This was possible by introducing a new parameter in the existing tensile strength and elastic modulus models. A wide range of lubrication conditions was explored and the model exhibited a good predictability. The mechanical properties of lactose monohydrate tablets were noticeably dependent on particle size, unlike spray-dried lactose where little to almost no sensitivity to initial particle size was observed. The model is designed in a general fashion that can capture all the possible mechanical integrity behaviors in response to different lubrication conditions and initial particle size. Our model can be extended to all the powders that undergo different deformation mechanisms and is applicable for more complex pharmaceutical formulations.