Pharmaceutical salts of emoxypine with dicarboxylic acids

Авторы публикации: 
Manin A. N., Voronin A. P., Drozd K. V., Churakov A. V., Perlovich G. L.
Acta Crystallographica Section C-Structural Chemistry
Год публикации: 
V. 74. -- P. 797-806.

New salt forms of the anti­oxidant drug emoxypine (EMX, 2-ethyl-6-methyl­pyridin-3-ol) with pharmaceutically acceptable maleic (Mlt), malonic (Mln) and adipic (Adp) acids were obtained {emoxypinium maleate, C8H12NO+·C4H3O4−, [EMX+Mlt], emoxypinium malonate, C8H12NO+·C3H3O4−, [EMX+Mln], and emoxypinium adipate, C8H12NO+·C6H9O4−, [EMX+Adp]} and their crystal structures determined. The mol­ecular packing in the three EMX salts was studied by means of solid-state density functional theory (DFT), followed by QTAIMC (quantum theory of atoms in mol­ecules and crystals) analysis. It was found that the major contribution to the packing energy comes from pyridine–carboxyl­ate and hy­droxy–carboxyl­ate heterosynthons forming infinite one-dimensional ribbons, with [EMX+Adp] additionally stabilized by hydrogen-bonded C(9) chains of Adp− ions. The melting processes of the [EMX+Mlt] (1:1), [EMX+Mln] (1:1) and [EMX+Adp] (1:1) salts were studied and the fusion enthalpy was found to increase with the increase of the calculated lattice energy. The dissolution process of the EMX salts in buffer (pH 7.4) was also studied. It was found that the formation of binary crystals of EMX with di­carb­oxy­lic acids increases the EMX solubility by more than 30 times compared to its pure form.

Колкер Римма Семеновна