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

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.

Solubility, Hansen Solubility Parameters and Thermodynamic Behavior of Emtricitabine in Various (Polyethylene Glycol-400 + Water) Mixtures: Computational Modeling and Thermodynamics

“…The diffraction angle (2θ) range for this analysis was set at 3 • −120 • with a scan speed of 1.0 • min −1 for both samples. The rest of the operation and condition was similar to those reported in our previous article [29].…”

“…The results of XRD analysis also showed that ECT was not transformed into polymorphs/hydrates/solvates after saturation. Overall, the XRD spectra of pure and equilibrated ECT suggested that the physical form of the ECT remained unchanged after solubility experiments [29]. .…”

“…Highest x e of ECT was recorded in pure PEG-400 (1.45 × 10 −1 at "T = 318.2 K"), whereas, the lowest one was observed in pure water (7.95 × 10 −3 at "T = 298.2 K"). Highest x e of ECT in pure PEG-400 could be possible due to lower polarity and lower Hansen solubility parameter (HSP) of PEG-400 in comparison with same physicochemical parameters of water [7,29]. The impact of mass fraction value of PEG-400 (m) on the solubility of ECT at "T = 298.2 to 318.2 K" was also investigated and resulting data is summarized in Figure 3.…”

“…The effect of pressure on ECT solubility was not evaluated in the current work and; therefore, current work was performed at fixed air pressure (i.e., "p = 0.1 MPa"). The investigated temperature ranges of "T = 298.15 K to 318.15 K" were selected randomly with the interval of 5.0 K in such a manner that the highest studied temperature (i.e., "T = 318.2 K") should not exceed the fusion temperature of ECT and boiling points of the investigated solvents (i.e., water and PEG-400 in this case) [6,29]. The fusion temperature of ECT was obtained as 427.80 K by thermal analysis.…”

Experimental and Computational Approaches for Solubility Measurement of Pyridazinone Derivative in Binary (DMSO + Water) Systems

“…The solubility data and other physicochemical properties of PPD have been reported poorly in the literature. The solubility of PPD in neat DMSO and neat water has been reported recently [17]. The solubility and solution thermodynamic properties of PPD in various DMSO + water systems are not reported elsewhere.…”