Salicylamide Cocrystals: Screening, Crystal Structure, Sublimation Thermodynamics, Dissolution, and Solid-State DFT Calculations

A new
cocrystal of 2-hydroxybenzamide (A) with 4-acetamidobenzoic
acid (B) has been obtained by the DSC screening method. Thermophysical
analysis of the aggregate [A:B] has been conducted and a fusion diagram
has been plotted. Cocrystal formation from melts was studied by using
thermomicroscopy. A cocrystal single-crystal was grown and its crystal
structure was determined. The pattern of noncovalent interactions
has been quantified using the solid-state DFT computations coupled
with the Bader analysis of the periodic electron density. The sublimation
processes of A-B cocrystal have been studied and its thermodynamic
functions have been calculated. The classical method of substance
transfer by inert gas-carrier was chosen to investigate sublimation
processes experimentally. The lattice energy is found to be 143 ±
4 kJ/mol. It is lower than the sum of the corresponding values of
the cocrystal pure components. The theoretical value of the lattice
energy, 156 kJ/mol, is in reasonable agreement with the experimental
one. A ternary phase diagram of solubility (A-B–ethanol) has
been plotted and the areas with solutions for growing thermodynamically
stable cocrystals have been determined.