An Assessment Of Forcite Approaches In Predictiing Young’s Modulus From Crystal Structure

Abstract

Improving the efficiency of tablet manufacturing in pharmaceutical industry has always attracted great concern. The mechanical properties of drugs are important for successful tablet production Thus, the knowledge of mechanical properties of pharmaceutical compound in pre-formulation stage facilitates tablet formulation development. A fast and accurate computational method for predicting crystal mechanical properties from crystal structure is extremely valuable since the availability of pharmaceutical active ingredients (APIs) is usually very limited. Methods based on the potential surface energy simulation are fast but their accuracy has not been systematically evaluated using a large set of crystals. The goal of the current study was to evaluate accuracy of predicted Young’s modulus (E) using the Forcite module in commercial software, Material Studio. The predicted E values of 50 organic crystals were compared to experimental values obtained by nanoindentation to assess their accuracy. A method to predict the E values on specific crystal faces was established to improve correlation by accounting for anisotropy of crystal mechanical properties. The correlation with experimental values remained poor. Detailed analyses of calculated E map of three crystals still failed to produce accurate E. Thus, the current Forcite module in Materials Studio for routine crystal form screening should be used with caution.