Detailed Study on Synthesis, Characterization and Solubility Determination of 6-phenyl-pyridazin-3(2H)-one in Different Pharmaceutical Solvents

Abstract

This study proposed the synthesis, characterization, solubility determination and solution thermodynamic properties of a cardiovascular drug 6-phenylpyridazin-3(2H)-one (PPD) in twelve different pharmaceutical solvents at temperatures “T = 298.2-318.2 K” and pressure “p = 0.1 MPa”. The measured solubilities of PPD were regressed well with “van’t Hoff and Apelblat models”. The solid phases of pure and equilibrated PPD were characterized using differential scanning calorimetry and powder X-ray diffractometry and results indicated no transformation of PPD into solvates/hydrates/polymorphs after equilibrium. The solubilities of PPD in mole fraction at “T = 318.2 K” were found to be maximum in dimethyl sulfoxide [DMSO] (0.473) followed by polyethylene glycol-400 [PEG-400] (0.412), Transcutol^® (0.346), ethyl acetate [EA] (6.81 x 10^-2), 2-butanol (2.18 x 10^-2), 1-butanol (2.11 x 10^-2), propylene glycol [PG] (1.50 x 10^-2), isopropyl alcohol [IPA] (1.44 x 10^-2), ethylene glycol [EG] (1.27 x 10^-2), ethanol (8.22 x 10^-3), methanol (5.18 x 10^-3) and water (1.26 x 10^-5). Similar trends were also recorded at other temperatures studied. The results of thermodynamic evaluation showed an endothermic and entropy-driven dissolution of PPD in all pharmaceutical solvents. The results of activity coefficients indicated maximum interaction at molecular level in PPD-DMSO, PPD-PEG-400 and PPD-Transcutol compared with other combination of solute and solvents studied. In conclusion, the results of this study indicated that pharmaceutical solvents such as DMSO, PEG-400 and Tarnscutol could be successfully utilized in the solubilization of PPD.