Abstract
Cocrystals of acemetacin drug (ACM) with nicotinamide (NAM), p-aminobenzoic acid (PABA), valerolactam (VLM) and 2-pyridone (2HP) were prepared by melt crystallization and their X-ray crystal structures determined by high-resolution powder X-ray diffraction. The powerful technique of structure determination from powder data (SDPD) provided details of molecular packing and hydrogen bonding in pharmaceutical cocrystals of acemetacin. ACM-NAM occurs in anhydrate and hydrate forms, whereas the other structures crystallized in a single crystalline form. The carboxylic acid group of ACM forms theacid-amide dimer three-point synthon R32(9)R22(8)R32(9) with three different syn amides (VLM, 2HP and caprolactam). The conformations of the ACM molecule observed in the crystal structures differ mainly in the mutual orientation of chlorobenzene fragment and the neighboring methyl group, being anti (type I) or syn (type II). ACM hydrate, ACM-NAM, ACM-NAM-hydrate and the piperazine salt of ACM exhibit the type I conformation, whereas ACM polymorphs and other cocrystals adopt the ACM type II conformation. Hydrogen-bond interactions in all the crystal structures were quantified by calculating their molecular electrostatic potential (MEP) surfaces. Hirshfeld surface analysis of the cocrystal surfaces shows that about 50% of the contribution is due to a combination of strong and weak O⋯H, N⋯H, Cl⋯H and C⋯H interactions. The physicochemical properties of these cocrystals are under study.
Highlights
Cocrystallization is a standard strategy to tailor physicochemical properties of drugs based on their chemical constituents (Childs et al, 2004; Duggirala et al, 2016; Bolla & Nangia, 2016) and supramolecular structure through crystal engineering (Desiraju et al, 2011; Desiraju, 2013)
acemetacin drug (ACM) tends to form a hydrate during any kind of solution- fore, high-resolution powder diffraction data were collected to based cocrystal preparation, and so its crystallization was solve the crystal structure of ACM–p-aminobenzoic acid (PABA) and nicotinamide carried out in strictly anhydrous melt conditions. cocrystals
We report crystal structures of acemetacin cocrystals listed in Scheme 1 from high-resolution powder diffraction data
Summary
Cocrystallization is a standard strategy to tailor physicochemical properties of drugs based on their chemical constituents (Childs et al, 2004; Duggirala et al, 2016; Bolla & Nangia, 2016) and supramolecular structure through crystal engineering (Desiraju et al, 2011; Desiraju, 2013). Structure solution from powder diffraction data for acemetacin cocrystals is reported in this paper as part of our continuing studies on this system (Sanphui et al, 2013, 2014). ACM tends to form a hydrate during any kind of solution- fore, high-resolution powder diffraction data were collected to based cocrystal preparation, and so its crystallization was solve the crystal structure of ACM–PABA and nicotinamide carried out in strictly anhydrous melt conditions (solventless). 0.0183/0.0236/0.0173 1.365 with three-dimensional coordinates determined have been reported using high-resolution powder data (David & Shankland, 2008; Braga et al, 2012; Chernyshev et al, 2013) In this background, we report crystal structures of acemetacin cocrystals listed in Scheme 1 (part b) from high-resolution powder diffraction data
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