Utilization of oriented crystal growth for screening of aromatic carboxylic acids cocrystallization with urea

• Oriented samples are used for co-crystal screening of urea with benzoic acid analogues.
• Proposed approach is efficient, robust, fast and cost-preserving.
• Validation of positive and negative cases confirms efficacy of proposed approach.
• New co-crystals of urea are identified based on PXRD and FTIR.
• Urea co-crystalize with 3-OH-, 2,4-diOH-, 2,5-diOH-, 2,6-diOH and 3,5-diOH-benzoic acids.

The possibility of molecular complex formation in the solid state of urea with benzoic acid analogues was measured directly on the crystallite films deposited on the glass surface using powder X-ray diffractometry (PXRD). Obtained solid mixtures were also analyzed using Fourier transform infrared spectroscopy (FTIR). The simple droplet evaporation method was found to be efficient, robust, fast and cost-preserving approach for first stage cocrystal screening. Additionally, the application of orientation effect to cocrystal screening simplifies the analysis due to damping of majority of diffraction signals coming from coformers. During validation phase the proposed approach successfully reproduced both positive cases of cocrystallization (urea:salicylic acid and urea:4-hydroxy benzoic acid) as well as pairs of co-formers immiscible in the solid state (urea:benzoic acid and urea:acetylsalicylic acids). Based on validated approach new cocrystals of urea were identified in complexes with 3-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid, 2,6-dihydroxybenzoic acid and 3,5-dihydroxybenzoic acid. In all cases formation of multicomponent crystal phase was confirmed by the appearance of new reflexes on the diffraction patterns and FTIR absorption band shifts of O–H and N–H groups.