The influence of molecular properties on the mean yield pressure of drugs - are issues of compressibility predictable based on chemical structure?

This article aims to predict the mean yield pressure during tableting using solely the chemical structure. Diverse chemical predictors were calculated using molecular modeling tools and the mean yield pressure was estimated by a partial least square analysis. The model revealed the relevant parameters for plastic deformation during tableting. Accordingly, the number of torsional bonds, molar volume, molecular weight, melting point, and cohesive energy had greatest impact on the mean yield pressure. The response surface plots of these predictors indicated that mainly drugs of lower molecular weight (< 200), higher melting point (> 200 °C), and having a low number of torsional bonds (< 4) result in high mean yield pressures. Such a lack of plastic deformation could lead to issues of compressibility, especially if tablets with a high drug load are targeted. These findings could be used in the future with regards to drug candidate selection and in view of planning the technical drug development.