Quantification of lubrication and particle size distribution effects on tensile strength and stiffness of tablets

Abstract

We adopt a Quality by Design (QbD) paradigm to better control the mechanical properties of tablets. To this end, the effect of particle size distribution, lubricant concentration, and mixing time on the tensile strength and elastic modulus of tablets is studied. Two grades of lactose, monohydrate and spray-dried, are selected. Tablets are compressed to different relative densities ranging from 0.8 to 0.94 using an instrumented compaction 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 is possible by introducing a new dimensionless parameter in the existing tensile strength and elastic modulus relationships with relative density. A wide range of lubrication conditions is explored and a predictable model is calibrated. The mechanical properties of lactose monohydrate tablets are noticeably dependent on particle size, unlike spray-dried lactose where little to almost no sensitivity to particle size is observed. The model is designed in a general fashion that can capture mechanical quality attributes in response to different lubrication conditions and particle size, and it can be extended to powders than undergo different deformation mechanisms, complex mixtures, and doubly convex tablets. Therefore, the model can be used to map the achievable design space of any given formulation.