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
German L. Perlovich
Abstract
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.