Prediction of Mefenamic Acid Crystal Shape by Random Forest Classification

Abstract

Abstract Objective Particle shape can have a significant impact on the bulk properties of materials. This study describes the development and application of machine-learning models to predict the crystal shape of mefenamic acid recrystallized from organic solvents. Methods Crystals were grown in 30 different solvents to establish a dataset comprising solvent molecular descriptors, process conditions and crystal shape. Random forest classification models were trained on this data and assessed for prediction accuracy. Results The highest prediction accuracy of crystal shape was 93.5% assessed by fourfold cross-validation. When solvents were sequentially excluded from the training data, 32 out of 84 models predicted the shape of mefenamic acid crystals for the excluded solvent with 100% accuracy and a further 21 models had prediction accuracies from 50–100%. Reducing the feature set to only solvent physical property descriptors and supersaturations resulted in higher overall prediction accuracies than the models trained using all available or another selected subset of molecular descriptors. For the 8 solvents on which the models performed poorly (< 50% accuracy), further characterisation of crystals grown in these solvents resulted in the discovery of a new mefenamic acid solvate whereas all other crystals were the previously known form I. Conclusions Random forest classification models using solvent physical property descriptors can reliably predict crystal morphologies for mefenamic acid crystals grown in 20 out of the 28 solvents included in this work. Poor prediction accuracies for the remaining 8 solvents indicate that further factors will be required in the feature set to provide a more generalized predictive morphology model.