Racemic salts and solid solutions of enantiomers of the antihypertensive drug carvedilol
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Universidade Federal de Minas Gerais
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Artigo de periódico
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Resumo
The R and S enantiomers of the antihypertensive drug carvedilol (CVD) can display remarkable miscibility in the crystalline state allowing this active pharmaceutical ingredient (API) to form a solid-solution of enantiomers (SSEs) as well as racemic compounds. Although rare and still little explored, these intriguing systems can also be used to design racemic multicomponent crystal forms toward the improvement of undesirable pharmaceutical properties of APIs. In this study, aiming to understand why there is miscibility between the enantiomers during the supramolecular recognition and crystallization processes of the CVD in the presence of salt formers, two SSEs and one racemic salt were prepared from the reaction of CVD with pharmaceutically acceptable HCl, HBr, and oxalic acids. Two monohydrated isostructural salts, hydrochloride (CVD-HCl-H2O) and hydrobromide (CVD-HBr-H2O), crystallize as racemic SSEs. These unique systems are formed from the miscibility of the R···R and S···S homochiral units that propagate into enantiomerically enriched one-dimensional chains through H-bonds with water molecules along the crystal. The oxalate salt (CVD-OXA), in turn, crystallizes as a standard racemic compound since the oxalate anions, which lie in the inversion center, are directly H-bonded to both R and S CVD enantiomers, forming racemic ionic units that extend along the structure. Complementary to the crystallographic study, conformational and Hirshfeld surface analysis were also performed based on the single-crystal X-ray diffraction data. The salt formations were confirmed from the Fourier transform infrared spectroscopy as well as powder X-ray diffraction patterns, and their thermal behaviors were investigated by a combination of differential scanning calorimetry, thermogravimetric, and hot-stage microscopy techniques.
Abstract
Assunto
Química analítica, Ácido tartárico, Ácido oxálico, Enantiômeros, Agentes hipotensores, Cristalografia, Análise conformacional, Raios X - Difração, Fourier, Espectroscopia de infravermelho por transformada de, Microscopia, Termogravimetria, Calorimetria, Deposição química de vapor, Estrutura molecular, Cristais, Farmacologia, Medicamentos - Análise
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Carvedilol, Solid solutions, Enantiomers, X-ray diffraction, Crystal structure, Chemical vapor deposition, Crystals, Molecular structure, Salts
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https://pubs.acs.org/doi/10.1021/acs.cgd.9b00263