INVESTIGADORES
CHATTAH Ana Karina
artículos
Título:
Solution and solid state properties of a set of procaine and procainamida derivatives
Autor/es:
M.E. OLIVERA; M. RIGO; A.K. CHATTAH; P.R. LEVSTEIN; M. BASCHINI; R.H. MANZO
Revista:
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Editorial:
Elsevier
Referencias:
Año: 2003 vol. 18 p. 337 - 348
ISSN:
0928-0987
Resumen:
A set of potential Class III antiarrhythmic agents of structure p-HOOCRCONHC6H4 COXC2H5 N(C2H5)2 were isolated as crystalline solids of the amide and ester derivatives, I: succinylprocainamide (X =NH, R = C H); II: succinylprocaine (X =O, R =C2H4); III: maleylprocainamide (X=NH, R=C2H2) and IV: maleylprocaine (X= O, R= C2H2). Although compounds IIV exhibit similar solution properties (i.e. acidbase speciation, with zwitterionic (+-) to neutral form (00) ratios higher than 10^4 ), aqueous solubility of NH derivatives is significantly higher than that of O derivatives and also, solvent effects on solubility (i.e. the change of water by ethanol) is clearly different in both series. Solution and solid-state properties of IIV were characterized to account for the observed differences. Results indicate that procainamide derivatives I and III crystallizes as (+-) but procaine derivatives II and IV s as (00) . Besides, I is anhydrous but IIIV are hydrates. Aqueous solubility and solvent effect on solubility are controlled by the intrinsic s solubility of the species (+-) in I and III and (00) in II and IV. The rise of hydrophilicity of species (00) due to the structural change from O to NH would determine the change in the structure of the precipitating crystals from (00) to (+-) . Solid structures (zwitterionic or neutral), as well as composition (anhydrous or hydrated) may be recognized as the main factors in determining the rank of aqueous solubility of the set.