Two-Component Molecular Crystals: What Is the Difference between Drug-Drug, Drug-GRAS, and CF-CF Databases? Evaluation of Melting Points and Ideal Solubility of Unknown Co-crystals

Based on literature analysis, we have built a database containing fusion temperatures and enthalpies of two-component molecular co-crystals and individual compounds (2170 co-crystals). The distribution functions of two-component crystals have been analyzed using their fusion temperatures, both for the database as a whole and separately for Drug-Drug, Drug-generally recognized as safe (GRAS), Drug-CF, and CF1-CF2 databases. A comparative analysis has been done of the co-crystal distribution by classes of compounds, I (Between), II (Higher), and III (Low), for the general database and six small databases. Correlation equations connecting the melting points of the co-crystals and individual components have been obtained, which has enabled us to design co-crystals with predictable melting temperatures. The effect of the difference between the melting temperatures of individual co-crystal components on the probability of formation of co-crystals of different groups (I-III) has been analyzed. An approach has been developed for evaluating the ideal solubility of co-crystals based on the knowledge of the ideal solubility of one of the co-crystal individual components only.

Automated summary

By analyzing the fusion temperatures and enthalpies of two-component molecular co-crystals, a database has been built for predicting co-crystals with predictable melting temperatures. The correlation equations connecting the melting points of co-crystals and individual components have been obtained. An approach for evaluating the ideal solubility of co-crystals based on the ideal solubility of one of the co-crystal individual components has been developed.