title: Cocrystal screening of hydroxybenzamides with benzoic acid derivatives: a comparative study of thermal and solution-based methods.
abstract: The main problem occurring at the early stages of cocrystal search is the choice of an effective screening technique. Among the most popular techniques of obtaining cocrystals are crystallization from solution, crystallization from melt and solvent-drop grinding. This paper represents a comparative analysis of the following screening techniques: DSC cocrystal screening method, thermal microscopy and saturation temperature method. The efficiency of different techniques of cocrystal screening was checked in 18 systems. Benzamide and benzoic acid derivatives were chosen as model systems due to their ability to form acid-amide supramolecular heterosynthon. The screening has confirmed the formation of 6 new cocrystals. The screening by the saturation temperature method has the highest screen-out rate but the smallest range of application. DSC screening has a satisfactory accuracy and allows screening over a short time. Thermal microscopy is most efficient as an additional technique used to interpret ambiguous DSC screening results. The study also included an analysis of the influence of solvent type and component solubility on cocrystal formation.
authors.affiliation: G.A. Krestov Institute of Solution Chemistry of the Russian academy of Sciences, 1, Akademicheskaya, 153045 Ivanovo, Russian Federation.
authors.forename: Alex N
authors.initials: AN
authors.lastname: Manin
authors.affiliation: G.A. Krestov Institute of Solution Chemistry of the Russian academy of Sciences, 1, Akademicheskaya, 153045 Ivanovo, Russian Federation.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Voronin
authors.affiliation: Ivanovo State University, 39, Ermaka, 153025 Ivanovo, Russian Federation.
authors.forename: Ksenia V
authors.initials: KV
authors.lastname: Drozd
authors.affiliation: G.A. Krestov Institute of Solution Chemistry of the Russian academy of Sciences, 1, Akademicheskaya, 153045 Ivanovo, Russian Federation.
authors.forename: Nikolay G
authors.initials: NG
authors.lastname: Manin
authors.affiliation: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
authors.forename: Annette
authors.initials: A
authors.lastname: Bauer-Brandl
authors.affiliation: G.A. Krestov Institute of Solution Chemistry of the Russian academy of Sciences, 1, Akademicheskaya, 153045 Ivanovo, Russian Federation. Electronic address: glp@isc-ras.ru.
authors.forename: German L
authors.initials: GL
authors.lastname: Perlovich
mesh_terms: D001549:Benzamides / Q000737:chemistry*; D019817:Benzoic Acid / Q000737:chemistry*; D003460:Crystallization / Q000379:methods; D033362:Powder Diffraction / Q000379:methods; D012995:Solubility; D012996:Solutions / Q000737:chemistry*; D013696:Temperature; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D001549:Benzamides; D012996:Solutions; D019817:Benzoic Acid
keywords: Cocrystal; Melting process; Screening; Solubility