Nucleation control and separation of ethyl maltol polymorphs under different growth conditions through solution crystallization process in selected solvent environments

Abstract

The nucleation control, separation, and growth of three different polymorphic forms of ethyl maltol – a promising flavor enhancer in food materials and an intermediate in pharmaceutical materials – have been achieved through solution crystallization processes for the first time. To attain the required levels of supersaturation, solutions with selected solvents saturated at different temperatures were used, and various crystallization processes such as fast evaporation, slow evaporation, and quench cooling methods were employed. The solution with a high supersaturation level (σ ∼ 9.52) yielded crystal nucleation of the highly energetic monoclinic Form-I polymorph, which had a needle-like morphology. In comparison, the intermediate supersaturation level (σ ∼ 0.16) yielded the intermediately energetic trigonal Form-II polymorph, which had a prismatic-like morphology, and the low supersaturation level (σ ∼ 0.10) yielded the less energetic triclinic Form-III polymorph, which had a platy-like morphology. The experimentally identified morphologies of the nucleated polymorphs through in situ optical microscopic analysis were verified with the theoretically derived and predicted morphologies using Shape software and the Bravais–Friedel–Donnay–Harker (BFDH) model, respectively. The crystallographic structural confirmation of the grown polymorphs was carried out through powder X-ray diffraction and single-crystal X-ray structural refinement analyses. The thermal stability and polymorphic phase transformations between the grown polymorphs were studied through differential scanning calorimetry.