Melting points of one- and two-component molecular crystals as effective characteristics for rational design of pharmaceutical systems

Based on the review of the literature results the database of the fusion temperatures of two-component molecular crystals (1947 co-crystals) and individual components thereof was built up. To improve the design of co-crystals with predictable melting temperatures, the correlation equations connecting co-crystals and individual components melting points were deduced. These correlations were discovered for 18 co-crystals of different stoichiometric compositions. The correlation coefficients were analysed, and the conclusions about the main/determinative and slave components of a co-crystal were made. The comparative analysis of the melting points of co-crystals composed from the same components but with different stoichiometry showed a co-crystal melting temperature growth when increasing the content of a high-melting component. The differences in the melting temperatures were determined and discussed for the following: (a) monotropic polymorphic forms, (b) two-component crystals with the same composition and different stoichiometry, and (c) two-component crystals based on racemates and enantiomers. The database analysis revealed the active pharmaceutical ingredients (APIs) and co-formers (CFs) more particularly used for co-crystal design. The approach based on an efficacy parameter allowing the prediction of co-crystals with melting points lower than those of individual compounds was developed.</jats:p

Design of two-component molecular crystals with defined melting points

The approach proposed in this study disclosed opportunities to predict whether it is possible to obtain co-crystals/salts with melting temperatures above/below the melting temperatures of the individual components.</jats:p

Two-component molecular crystals: evaluation of the formation thermodynamics based on melting points and sublimation data

An approach to estimating co-crystal sublimation thermodynamic characteristics has been developed. The thermodynamic functions of the formation process of 281 co-crystals have been obtained and analyzed.</p