Solubility and Thermodynamics of 6-Phenyl-4,5-dihydropyridazin-3(2H)-one in Various (PEG 400+Water) Mixtures

Abstract

The aim of this study was to determine the solubility of pyridazinone derivative 6-phenyl-4,5-dihydropyridazin-3(2H)-one (PDP-6) in different “polyethylene glycol 400 (PEG 400)+water” mixtures at temperatures “T=293.2 K to 313.2 K” and pressure “p=0.1 MPa”. The solubilities of PDP-6 were determined using an isothermal method and correlated with Apelblat, van’t Hoff and Yalkowsky–Roseman models. The maximum solubilities of PDP-6 in mole fraction were obtained in neat PEG 400 (8.46×10−2 at T=313.2 K). However, the minimum one was recorded in neat water (7.50×10−7 at T=293.2 K). Apparent thermodynamic analysis showed an endothermic dissolution of PDP-6 in all (PEG 400 water) mixtures. Based on the solubility data of the current study, PDP-6 has been considered as practically insoluble in water and soluble in PEG 400.

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

“…The solubility values of a similar pyridazinone derivative, i.e., 6-phenyl-4,5-dihydropyridazin-3(2 H )-one, in eleven different pure solvents, namely “water, ethanol, IPA, EG, PG, PEG-400, 1-butanol, 2-butanol, EA, Transcutol and DMSO” at “ T = 293.2 K to 313.2 K” and “ p = 0.1 MPa”, have been reported elsewhere [20]. The solubilities of 6-phenyl-4,5-dihydropyridazin-3(2 H )-one in various “Transcutol + water” and “PEG-400 + water” binary solvent systems at “ T = 293.2 K to 313.2 K” and “ p = 0.1 MPa” were also reported [21,22]. Nevertheless, the solubilities of the investigated compound PPD in any of the neat solvent or binary solvent mixtures have not been reported.…”

“…The “Apelblat solubility ( x Apl )” of PPD was estimated using Equation (5) [30,31]:ln xApl= A+BT+ Cln(T), Here, A, B and C = model parameters of the “Apelblat model”. The values of A, B and C were estimated by applying a “nonlinear multivariate regression analysis” of the x e values of PPD, tabulated in Table 1 [22]. The correlation between the x e and x Apl values of PPD was conducted in terms of “root mean square deviations ( RMSD ) and the coefficient of determination ( R 2 )”.…”

“…However, the solubilities of a similar compound, 6-phenyl-4,5-dihydropyridazin-3(2 H )-one, have been recently reported by our research group in eleven different neat solvents including water, ethanol, isopropanol (IPA), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), 1-butanol, 2-butanol, ethyl acetate (EA), Transcutol and dimethyl sulfoxide (DMSO) at “ T = 293.2 K to 313.2 K” and “ p = 0.1 MPa” [20]. The solubilities and solution thermodynamic properties of 6-phenyl-4,5-dihydropyridazin-3(2 H )-one in different “Transcutol + water” and “PEG-400 + water” binary solvent systems at “ T = 293.2 K to 313.2 K” and “ p = 0.1 MPa” have also been reported [21,22].…”

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

“…The highest γ i of ECT in pure water could be possible due to the lowest solubility of ECT in water and higher dielectric constant/polarity of water compared with the highest solubility of ECT in PEG-400 and lower dielectric constant/polarity of neat PEG-400 [15,17]. The results of activity coefficients for ECT in various "PEG-400 + water" mixtures were found in accordance with their dielectric constants and mole fraction solubility [15]. Based on these results, the maximum solute-solvent interactions were found in ECT-PEG-400 compared with ECT-water.…”

“…"Polyethylene glycol-400 (PEG-400)" has been reported as an efficient cosolvent in solubilization of drugs in aqueous media and it is miscible with water in all proportions [9][10][11]. The potential of PEG-400 has been studied extensively in solubility enhancement of various drugs [9][10][11][12][13][14][15][16][17][18]. Several formulation approaches including "3D printed controlled release tablets [4], film coated tablets [19], rapidly disintegrating vaginal tablets [20], immediate release tablets [21], vaginal gels [22], liposomal gels [23], microparticulate drug delivery system [24], nanosuspensions [25,26] and polymeric nanoparticles [5,27,28]" were reported to improve antiviral therapy and pharmacokinetic profile of ECT.…”