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

6-苯基哒嗪-3(2H)-酮的合成、表征及在不同药物溶剂中的溶解度测定

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作者:Faiyaz Shakeel, Mohd Imran, Nazrul Haq, Sultan Alshehri, Md Khalid Anwer

Abstract

The current research work proposed the solubility data and solution thermodynamic properties of the cardiovascular agent 6-phenylpyridazin-3(2H)-one [PPD] in twelve pharmaceutical solvents at "T = 298.2 K to 318.2 K" and "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 differactometry, and the results suggested no transformation of PPD into solvates/hydrates/polymorphs after equilibrium. The solubilities of PPD in a mole fraction at "T = 318.2 K" were noted at a maximum in dimethyl sulfoxide (DMSO, 4.73 × 10-1), followed by polyethylene glycol-400 (PEG-400, 4.12 × 10-1), Transcutol® (3.46 × 10-1), ethyl acetate (EA, 81 × 10-2), 2-butanol (2.18 × 10-2), 1-butanol (2.11 × 10-2), propylene glycol (PG, 1.50 × 10-2), isopropyl alcohol (IPA, 1.44 × 10-2), ethylene glycol (EG, 1.27 × 10-2), ethanol (8.22 × 10-3), methanol (5.18 × 10-3) and water (1.26 × 10-5). Similar tendencies were also noted at other studied temperatures. The results of the "apparent thermodynamic analysis" showed an endothermic and entropy-driven dissolution of PPD in all pharmaceutical solvents. The results of the activity coefficients suggested a maximum interaction at the molecular level in PPD-DMSO, PPD-PEG-400 and PPD-Transcutol, compared with other combination of the solute and solvents.

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