Neat Solvents Research Articles

Comments on “Assessment of solubility and Hansen solubility parameters of rifampicin in various permeation enhancers: Experimental and computational approach”

A polemic is given regarding the published curve-fit equation coefficients for both the van’t Hoff and Modified Apelblat equations, as well as for the published apparent thermodynamic properties of dissolution of rifampicin in several neat permeation enhancers and in several neat organic solvents.

Solubility Behavior of Ethyl l-Thiazolidine-4-carboxylate Hydrochloride in 15 Neat Solvents and Ethanol + Methyl Acetate Binary Solvent from 283.15 to 323.15 K

The solubility (mole fraction) of ethyl l-thiazolidine-4-carboxylate hydrochloride in 15 individual solvents including water, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-...

Effect of the weak intermolecular C-H···O=C hydrogen bonding, solvent polarity and concentration on the frequency of the C=O stretch mode of 2-thiophenecarboxaldehyde

The vibrational frequency shift in the C=O stretch mode of 2-thiophenecarboxaldehyde (2TC) in the condensed phase is still not fully understood. In this paper, the vibrational spectra of 2TC were investigated using the FT-Raman, FT-IR and resonance Raman spectroscopies in conjunction with the density functional theory calculation. The pure compound (in the neat liquid) exhibits three vibrational bands 1658, 1672 and 1687 cm−1 in the νC=O spectral region. It differs from the band pair 1672 and 1682 cm−1 for 2-cyclohexene-1-one (CHO) and the single band 1700 cm−1 for benzaldehyde. The relative intensities of observed bands vary with the polarity of aprotic solvents and the compound’s concentration. In a diluted solution, the strongest band in the resonance Raman spectra of 2TC appears the C=O stretch mode at 1690 cm−1 in cyclohexane and 1674/1675 cm−1 in acetonitrile. The imparting factors that shift the C=O stretch mode frequency in the neat liquid and solvents with different polarities were examined. The spectral sources of the vibrational bands at 1658 and 1672 cm−1 in the neat liquid and a dilute solution were determined, and the resonance Raman spectra were assigned. It is concluded that tetramers and monomer are the major sources of the bands at 1658 and 1672 cm−1 in the neat liquid, respectively, while the monomer is the main source of the bands at 1674/1675 cm−1 in acetonitrile and the band at 1690 cm−1 in cyclohexane with a dilute concentration. The band’s source at 1662/1663 cm−1 in acetonitrile (a dilute concentration) can be either the dimers or 2TC-CH3CN clusters. The C=O bond’s electronic charge density is the main factor that shifts the vibrational frequency of the C=O stretch mode of 2TC monomer when an aprotic solvent is used. The larger the polarity of an aprotic solvent, the more negative the electronic charge-density of the C=O bond for the monomer, the lower the frequency of the C=O stretch mode.

Solubility Behavior and Polymorphism of N-Acetyl-l-proline in 16 Individual Solvents from 283.15 to 323.15 K

The mole fraction solubility data of N-acetyl-l-proline in 16 neat solvents (water, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, n-pentanol, acetone, 2-butanone, acetonitrile, dichloromethane, methyl acetate, ethyl acetate, and 1,4-dioxane) covering a temperature range of 283.15–323.15 K were measured by the static gravimetric method. The polymorphism of N-acetyl-l-proline was investigated by the powder X-ray diffraction test and the patterns show that there are two polymorphs within the studied solid–liquid equilibrium systems. The increasing temperature shows a positive effect on N-acetyl-l-proline solubility in all of the solvents and the largest increasing rate is observed in acetonitrile with an increase of 16-fold. The solubility behavior was found to be influenced by five factors including polarity, hydrogen bonding, solvent–solvent interactions, molecular construction, and viscosity. Two thermodynamic models, i.e., the modified Apelblat model and the Yaws model, were used for the correlation of solubility data. To evaluate the fitting results, the average relative deviation (ARD) and root-mean-square deviation (RMSD), as well as the Akaike information criterion (AIC) and Akaike weights, were computed for each model.

Solubility Determination and Thermodynamic Modeling of N-Acetylglycine in Different Solvent Systems

N-Acetylglycine solubility in 12 monosolvents (water, methanol, ethanol, n-propanol, i-propanol, n-butanol, i-butanol, s-butanol, n-pentanol, acetone, acetonitrile, and 1,4-dioxane) were determined by the static gravimetric method within the temperature range from 283.15 to 333.15 K under an ambient pressure of 98.8 kPa. In the meantime, the binary solvent mixture (methanol + acetonitrile) of different ratios was measured from 283.15 to 323.15 K. Analysis of the neat solvent data showed that the solubility behavior was influenced by the polarity, hydrogen bond, molecular structures, molecular steric hindrance, and so on. The KAT-LSER model was used to perform the multiple linear regression analysis on a pure solvent system to reveal the solvent effect on solubility. When the solvent composition was constant, a positive correlation of N-acetylglycine solubility with experimental temperature was found in all investigated pure and mixed solvent systems. At a given temperature, inflection points were found in the solubility curves for binary solvent systems as the mole fraction of methanol increased, which may be attributed to the cosolvency phenomenon. Six thermodynamic models, including the modified Apelblat, Yaws, Jouyban–Acree, Machatha, Apelblat–Jouyban–Acree, and Apelblat–Machatha models, were employed for fitting the solubility data.

Synthesis and (fluoro)solvatochromism of two 3-styryl-2-pyrazoline derivatives bearing benzoic acid moiety: A spectral, crystallographic and computational study

In this work we report the synthesis of two fluorescent 2-pyrazoline derivatives exhibiting remarkable (fluoro)solvatochromic behavior. The pyrazolines were synthesized in one step from the corresponding monocarbonyl curcuminoids and 4-hydrazinobenzoic acid in high yield and purity and were fully characterized by means of NMR and FT-IR spectroscopy and HRMS spectrometry. The structure of the novel derivative 2 was also characterized by means of X-ray crystallography. Both compounds were studied computationally in the gas phase. Additionally, the effects of solvent polarity on the absorption and fluorescence spectra of these derivatives were investigated in a solvent group consisting of various neat molecular solvents exhibiting hydrogen bond donating (HBD), hydrogen bond accepting (HBA), and/or dipolar behavior. The solvent effects observed were quantified and rationalized by employing suitable multiparametric Linear Solvation Energy Relationships (LSERs) involving dipolarity, HBD-acidity and HBA-basicity terms. The contribution of each of these parameters provided insights on the predominant solute-solvent interactions occurring in solution. Importantly, some differences in the (fluoro)solvatochromic aptitude/behavior were revealed among the derivatives and they were rationalized on the basis of their structural diversity.

Solubility Behavior of dl-Homocysteine Thiolactone Hydrochloride in Nine Pure and A Binary Methanol + Acetonitrile Solvent Systems

dl-Homocysteine thiolactone hydrochloride (one of the derivatives of l-cysteine) solubility in nine neat solvents (methanol, ethanol, isopropanol, ethyl acetate, 1,4-dioxane, acetonitrile, acetone,...

Thermodynamic analysis and molecular simulation of solid–liquid phase equilibrium of isoprenaline hydrochloride in eleven pure solvents at saturation

In this research, the solubility of isoprenaline hydrochloride (IPN) in eleven neat solvents was investigated by using experimental and molecular dynamic (MD) simulation analysis approaches. The experimental solubility data of IPN in eleven neat solvents of methanol, 2-methoxyethanol, ethanol, 2-ethoxyethanol, n-propanol, 2-propoxyethanol, n-butanol, 2-butoxyethanol, N, N-dimethylformamide (DMF), N-N-Dimethylacetamide (DMAC) and 1-Methyl-2-pyrrolidinone (NMP) were determined by laser monitoring method at temperature range of (278.15 K–323.15 K) under atmospheric pressure. The solubility values were sensitive to temperature, namely, increased monotonously with increasing temperature. The order of IPN solubility at each temperature point in selected solvents is: DMAC > DMF > NMP > methanol > 2-methoxyethanol > ethanol > 2-ethoxyethanol > 2-propoxyethanol > n-propanol > 2-butoxyethanol > n-butanol. Then, the measurement solubility data was correlated by Two-Suffix Margules model, NRTL-SAC model, Yaws model, λh equation and Apelblat equation, respectively. The derived apparent thermodynamic parameters (ΔdisGo, ΔdisHo, ΔdisSo, ζH, ζTS) shown an entropy-driven, endothermic and spontaneous process of dissolution of IPN in all chosen solvents. And the main contribution of ΔdisGo comes from the positive enthalpy according the larger ζH than ζTS. Furthermore, the results of molecular dynamic simulation revealed using radial distribution function (RDF) analysis, which indicated that interactions of solvent–solute have well fitted with solubility order of IPN in selected solvents.

Uridine in twelve pure solvents: Equilibrium solubility, thermodynamic analysis and molecular simulation

in this work, the solubility of uridine in twelve neat solvents was investigated by using experimental laser monitoring method and molecular dynamic (MD) simulation analysis approach. The experimental solubility data of uridine in twelve neat solvents, including methanol, 2-methoxyethanol, ethanol, 2-ethoxyethanol, n-propanol, 2-propoxyethanol, isopropanol, n-butanol, 2-butoxyethanol, ethylene glycol, N, N-dimethylformamide (DMF) and water, was measured at temperature range of (278.15 K–323.15 K) under atmospheric pressure. The solubility of uridine was sensitive to temperature in tested solvents, namely, increased monotonously with rising temperature. The order of uridine solubility at 298.15 K in selected solvents is DMF (0.1780) > water (0.04061) > 2-methoxyethanol (0.01565) > ethylene glycol (0.01399) >2-ethoxyethanol (0.006413) > methanol (0.003195) > 2-propoxyethanol (0.003005) > 2-butoxyethanol (0.002241) > isopropanol (0.001238) > ethanol (0.001086) > n-propanol (0.001047) > n-butanol (0.0009806). the measurement solubility data was correlated by NRTL model, NRTL-SAC model, UNIQUAC model, λh equation and Apelblat equation, respectively. The derived apparent thermodynamic parameters (ΔdisGo, ΔdisHo, ΔdisSo, ζH, ζTS) shown an entropy-driven, endothermic and spontaneous process of dissolution of uridine in all chosen solvents, and the main contribution of ΔdisGo comes from the positive enthalpy. Hansen solubility parameters (HSPs) were employed to reveal the solubility phenomenon of uridine in selected solvents. Furthermore, the results of molecular dynamic simulation revealed using radial distribution function (RDF) analysis, which indicated that interactions of solvent-solute have well fitted with solubility order of uridine in selected solvents.

N-Doped Yellow-Emissive Carbon Nanodots from Gallic Acid: Reaction Engineering, Stimuli-Responsive Red Emission, and Intracellular Localization

An easy one-pot method is utilized for the synthesis of carbon nanodots, which has been investigated primarily from material perspectives. However, this preferred one-pot synthesis method suffers from the untraceability of steps leading to the infusion of the photoluminescence property in the nanodot. To resolve the steps involved, a single-precursor approach has been adopted here for the synthesis of the yellow-fluorescent probe by using a bioresource, gallic acid. The synthesized probe exhibits excitation-energy-independent emission, a typical molecular behavior, but shows an emission-wavelength-dependent lifetime that is often attributed to the red-edge effect most commonly observed for nanodots. We propose here that the observation of the red-edge effect for a synthesized probe in neat solvents is due to proton-transfer controlled solvation, a unique photoprocess. Characterization and computational results of the synthesized product clearly suggest the formation of a molecular fluorophore. Unprecedentedly, the synthesized probe shows proton-triggered red emission. The addition of a proton resulted in molecular aggregation due to a strong H-bonded interaction among product molecules. The presence of multiple phenolic−OH groups in the probe allows the easy formation of molecular chains of crystals on transmission electron microscopy grids, causing the observation of lattice spacing that remains unchanged in an aggregated state as well. We have also explored its possible applications in bioimaging and trivalent metal ion sensing. It has better cell-membrane permeability but remains predominantly in the cytoplasm. Both green and red fluorescence are observed inside the cell. The product molecule possesses a submicromolar detection limit for aluminum ions as well, further confirming the unaltered position of phenolic–OH groups present in the product and substrate.

Solid–Liquid Equilibrium of l-Thioproline in Nine Neat Solvents and Water + Acetonitrile Binary Solvent System from 283.15 to 323.15 K: Solubility Determination and Data Modeling

The data on the solubility of l-thioproline in a mole fraction scale in nine individual solvents (water, methanol, ethanol, isopropanol, acetone, acetonitrile, dichloromethane, ethyl acetate, and 1...

Equilibrium solubility, Hansen solubility parameter, dissolution thermodynamics, transfer property and preferential solvation of zonisamide in aqueous binary mixtures of ethanol, acetonitrile, isopropanol and N,N-dimethylformamide

The present contribution was devoted to the equilibrium solubility profile, thermodynamics of dissolution process and solvation performance of zonisamide in aqueous binary mixtures of acetonitrile, ethanol, isopropanol and N,N-dimethylformamide (DMF) by using experiment and mathematical correlations. A shake-flask method was used throughout all experimental process under ambient pressure of 101.2 kPa from 278.15 to 323.15 K. The maximum magnitude of equilibrium solubility of zonisamide in neat acetonitrile/ethanol/isopropanol/DMF at T = 323.2 K was recorded as 23.28 × 10−3, 4.460 × 10−3, 3.522 × 10−3 and 136.4 × 10−3 (mole fraction), respectively; while the minimum one was recorded in pure solvent of water (0.01783 × 10−3 at 278.15 K). The solubility behavior of the drug zonisamide was analyzed through Hansen solubility parameter. The solubility data was represented computationally by various models such as the modified Jouyban–Acree–van’t Hoff, Jouyban–Acree, and general single model (GSM), achieving the overall relative average deviations of less than 8.23 %. The relative prominence of interactions of solvent-solvent and solute-solvent molecules upon zonisamide solubility studied through the linear solvation energy relationships indicated that the chief contributions to solubility variation were dipolarity-polarizability and solubility parameter of solutions. The determined solubility data at 298.15 K was analyzed by using the extended Hildebrand solubility approach gaining correlation coefficient of 0.86. According to several solution properties, a quantitative study on preferential solvation was performed by the technique of inverse Kirkwood–Buff integrals. The preferential solvation parameters for neat solvents of isopropanol, acetonitrile, ethanol and DMF were positive in isopropanol/acetonitrile/ethanol/DMF-rich and intermediate proportions in solutions, suggesting that the drug zonisamide was preferentially solvated by the cosolvents (isopropanol/acetonitrile/ethanol/DMF). In these composition regions, it is conjectured that zonisamide is acting as a Lewis acid with the molecules of isopropanol/acetonitrile/ethanol/DMF. Thermodynamic dissolution calculation exhibited an entropy-driven and endothermic dissolution of the drug zonisamide in all the isopropanol/acetonitrile/ethanol/DMF + water mixtures. In addition, the evaluation of enthalpy–entropy compensation specified an enthalpy-driven mechanism for the solvation of zonisamide. The investigation on transfer properties indicated more advantageous solubilization capability in intermediate proportions of isopropanol/acetonitrile/ethanol/DMF.

Insilico Anti-COVID Study of New-fangled High Polar Zr(IV) Complexes Functionalized with Resacetophenone and NMP Ligands

A significant issue restricting their commercialization is the short dependability of utilitarian biomolecules. These days, enduring immunizations, antiviral specialists, and anti-infection agents without zero results are intriguing examination subjects. In continuation of our pandemic exploration interest focused on the advancement of the keen antiviral specialist for COVID-19 utilizing heterocyclic metal builds. We describe herein synthesis and structural characterization of two new Zr(IV) complexes containing ligands like resacetophenone (T-R-Zr) (I) and N-methyl-2-pyrrolidone (T-NMP-Zr) (II). The absorption character in a neat solvent, in presence of 4.5 % BSA, and the biological interaction of COVID-19 virus through molecular docking have been summarized taking the scope into coordination chemistry directly or indirectly. The two complexes in 4.5% of BSA display both blue and red shift in peaks corresponds to LCT and MLCT transitions. The molecular docking study of the complex with the crystal structure of SARS-Coronavirus-2 (PDB: 6LU7) shows strong polar interaction with various amino acids present in the spike protein. The complex shows excellent binding energies ranges in-7.0 and -4.9 kcal mol-1, respectively. This makes them potential lead compounds for development into candidates against the SARS-Coronavirus-2. The absorption spectral behavior insolvent and in 4.5 % BSA has been found to show the importance of our complex in biological application especially in COVID-19 treatment studies. Furthermore, we investigated the basic energies like potential and steric energy of the complex through Gaussian energy calculations.

Insilico Anti-COVID Study of New-fangled High Polar Zr(IV) Complexes Functionalized with Resacetophenone and NMP Ligands

A significant issue restricting their commercialization is the short dependability of utilitarian biomolecules. These days, enduring immunizations, antiviral specialists, and anti-infection agents without zero results are intriguing examination subjects. In continuation of our pandemic exploration interest focused on the advancement of the keen antiviral specialist for COVID-19 utilizing heterocyclic metal builds. We describe herein synthesis and structural characterization of two new Zr(IV) complexes containing ligands like resacetophenone (T-R-Zr) (I) and N-methyl-2-pyrrolidone (T-NMP-Zr) (II). The absorption character in a neat solvent, in presence of 4.5 % BSA, and the biological interaction of COVID-19 virus through molecular docking have been summarized taking the scope into coordination chemistry directly or indirectly. The two complexes in 4.5% of BSA display both blue and red shift in peaks corresponds to LCT and MLCT transitions. The molecular docking study of the complex with the crystal structure of SARS-Coronavirus-2 (PDB: 6LU7) shows strong polar interaction with various amino acids present in the spike protein. The complex shows excellent binding energies ranges in-7.0 and -4.9 kcal mol-1, respectively. This makes them potential lead compounds for development into candidates against the SARS-Coronavirus-2. The absorption spectral behavior insolvent and in 4.5 % BSA has been found to show the importance of our complex in biological application especially in COVID-19 treatment studies. Furthermore, we investigated the basic energies like potential and steric energy of the complex through Gaussian energy calculations.

Solubility of sulfadiazine in (ethylene glycol + water) mixtures: Measurement, correlation, thermodynamics and preferential solvation

The equilibrium solubility of sulfadiazine (SD) in {ethylene glycol (EG) (1) + water (2)} mixtures at temperatures from (278.15 to 318.15) K is reported. Mole fraction solubility of SD (x3) increases with temperature arising and also increases with the EG proportion increasing. It varies from 4.81 × 10−6 in neat water to 5.32 × 10−4 in neat EG at 298.15 K. Solubility behavior was correlated by the extended log-linear model of Yalkowsky, the Jouyban-Acree model, and Jouyban-Acree-van't Hoff model and the obtained mean percentage deviations are 43.6%, 7.0% and 7.1%, respectively. From the variation of solubility with temperature the apparent thermodynamic analysis of dissolution and mixing was performed in all the mixtures and neat solvents. Based on the inverse Kirkwood-Buff integrals (IKBI) is observed that SD is preferentially solvated by water in water-rich mixtures (0.00 < x1 < 0.24) but preferentially solvated by EG in the interval (0.24 < x1 < 1.00).

Solubility Measurements and Correlation of MBQ-167 in Neat and Binary Solvent Mixtures.

MBQ-167 is a novel, small-molecule dual inhibitor of Rac and Cdc42, small GTPases that are involved in cytoskeletal organization, cell cycle progression, and cell migration. In an in vivo mouse model, MBQ-167 has been shown to significantly reduce mammary tumor growth and metastasis and is currently undergoing preclinical studies for the treatment of metastatic cancer. To date, no solubility data have been reported for this compound. For this reason, the present study aims to determine the solubility of this compound in eight neat solvents (acetonitrile, 1-butanol, 2-butanol, ethanol, ethyl acetate, methanol, 1-propanol, and 2-propanol) and two binary solvent mixtures [ethyl acetate (2) + heptane (3) and ethanol (2) + water (3)] between the temperatures of 278.15 and 333.15 K. The results obtained employing the polythermal method show that the solubility of MBQ-167 increases with an increase in temperature in all neat solvents used within this study. Moreover, in the two binary solvent mixtures, the solubility of this compound increases with increasing temperature and decreases with an increasing mass fraction of the antisolvent (heptane or water). The experimental solubility data were correlated using the modified Apelblat and λh model equations. The predicted solubility data acquired from the Apelblat and λh model equations correlate well with the experimental solubility data as indicated by the low ARD % (≤1.8304 and ≤6.5366, respectively). No solvent-mediated polymorphic phase transitions were observed while performing the solubility studies, and no other solid forms were detected after the recrystallization in the solvents and solvent mixtures. The solubility data determined here can offer pathways to develop pharmaceutical crystallization processes that can further the translation of MBQ-167 into a clinical setting.

Solvation and coordination chemistry of manganese(II) in some solvents. A transfer thermodynamic, complex formation, EXAFS spectroscopic and crystallographic study

The solvation and coordination chemistry of the manganese(II) ion in water, methanol, dimethylsulfoxide (dmso), N,N’-dimethylpropylene urea (dmpu), acetonitrile and N,N-dimethylthioformamide (dmtf) have been studied from solvation thermodynamic, structural and complex formation ability point of view by calorimetry and EXAFS spectroscopy. The heats of transfer from water to methanol, dmso, acetonitrile and dmtf have been determined to −37.7, −71.6, –23.1 and −36.3 kJ mol−1, respectively, from the heats dissolution of anhydrous manganese(II) trifluoromethanesulfonate by ampoule calorimetry in the neat solvents. Refinement of the EXAFS data of the hydrated and methanol and dmso solvated manganese(II) ions in solution show octahedral configuration and mean Mn-O bond distances of 2.165(3), 2.161(2) and 2.157(3) Å, respectively. The Mn-O bond distance is significantly shorter in dmpu solution, 2.087(3) Å. As dmpu is a space-demanding solvent upon coordination, the manganese(II) ion is only allowed to bind five dmpu molecules in the solvate complex. The acetonitrile solvated manganese(II) ion is six-coordinate in octahedral fashion in solution with a mean Mn-N bond distance of 2.193(3) Å. The relative permittivity of pyridine is too low to allow dissociation of salts of divalent metal ions and neutral pyridine solvated complexes are formed in pyridine solution. In concentrated manganese(II) trifluoromethanesulfonate dmtf solution a contact ion-pair is formed with one trifluoromethanesulfonate ion. In this complex manganese(II) binds five dmtf molecules and a trifluoromethanesulfonate oxygen with Mn-S and Mn-O bond distances of 2.598(6) and 2.16(1) Å, respectively, in an octahedral complex. Complex formation studies performed by titration calorimetry of the manganese(II)-bromide system show significantly more stable complexes in dmpu than in solvents where the solvated manganese(II) ion has regular octahedral symmetry. The dmpu solvated MnBr2 complex in dmpu solution is five coordinate with mean Mn-Br and Mn-O bond distances of 2.494(3) and 2.076(3) Å, respectively. The structure of the [MnBr2(dmpu)2] complex in solid state has distorted tetrahedral geometry with mean Mn-Br and Mn-O bond distances of 2.473(3) and 2.014(3) Å, respectively, and a Br-Mn-Br bond angle of 116.3(1) degrees.

Multicomponent Solid–Liquid Equilibrium of 1,3,5-Triformylbenzene—A Key Intermediate for Porous Organic Cages: Solubility Determination and Correlation in Different Solvent Systems

The multicomponent solid–liquid equilibrium data for 1,3,5-triformylbenzene, a key intermediate for the synthesis of porous organic cages, in 12 neat solvents (water, methanol, ethanol, n-propanol,...

An Investigation of the Influence of PEG 400 and PEG-6-Caprylic/Capric Glycerides on Dermal Delivery of Niacinamide.

Polyethylene glycols (PEGs) and PEG derivatives are used in a range of cosmetic and pharmaceutical products. However, few studies have investigated the influence of PEGs and their related derivatives on skin permeation, especially when combined with other solvents. Previously, we reported niacinamide (NIA) skin permeation from a range of neat solvents including propylene glycol (PG), Transcutol® P (TC), dimethyl isosorbide (DMI), PEG 400 and PEG 600. In the present work, binary and ternary systems composed of PEGs or PEG derivatives combined with other solvents were investigated for skin delivery of NIA. In vitro finite dose studies were conducted (5 μL/cm2) in porcine skin over 24 h. Higher skin permeation of NIA was observed for all vehicles compared to PEG 400. However, overall permeation for the binary and ternary systems was comparatively low compared with results for PG, TC and DMI. Interestingly, values for percentage skin retention of NIA for PEG 400:DMI and PEG 400:TC were significantly higher than values for DMI, TC and PG (p < 0.05). The findings suggest that PEG 400 may be a useful component of formulations for the delivery of actives to the skin rather than through the skin. Future studies will expand the range of vehicles investigated and also look at skin absorption and residence time of PEG 400 compared to other solvents.

Solid-liquid phase equilibrium of naphazoline hydrochloride in eleven neat solvents: Determination, solvent effect, molecular simulation and thermodynamic analysis

The purpose of this work was to measure the equilibrium solubility of naphazoline hydrochloride (NPZ) in different mono-solvents ranged from 278.15 K to 323.15 K by a laser monitoring method. In this research, N-methyl pyrrolidone (NMP), n-propanol, 2-butoxyethanol, ethanol, 2-methoxyethanol, N,N-dimethylformamide (DMF), methanol, ethylene glycol (EG), isopropanol, 2-propoxyethanol and 2-ethoxyethanol were selected as the experimental solvents. The results indicated that solubility data of NPZ in 11 neat solvents increased with the increase of temperature. At 298.15 K, the maximum solubility was observed in EG (5.028e-2), followed by 2-methoxyethanol (2.460e-2), methanol (2.429e-2), 2-ethoxyethanol (7.788e-3), ethanol (6.391e-3), 2-propoxyethanol (4.216e-3), n-propanol (3.373e-3), 2-butoxyethanol (3.144e-3), DMF (2.348e-3), NMP (2.002e-3) and isopropanol (1.689e-3). Moreover, the solvent polarity, radial distribution function (RDF) and solvent effect (KAT-LSER model) were implemented to investigate the impact of solute-solvent interactions on solubility behavior of NPZ. The results demonstrated that the whole dissolution behavior of NPZ in organic solvents was a complicated process, and the solvent-solute interactions were associated with hydrogen bond acidity and dipolarity/polarizability of solvent. Besides, the NRTL-SAC, Two-Suffix Margules, Wilson, NRTL and UNIQUAC models were employed to fit experimental solubility data. Deviation analysis revealed that the Wilson model reflected the best agreement between measured data and calculated values with the minimum mean values of average relative deviation (100ARD, 0.9144) and root-mean square deviation (104RMSD, 1.062). Furthermore, the positive entropy changes and negative values of Gibbs energy changes showed that mixing and dissolution process of NPZ in 11 neat solvents were confirmed to entropy-driven and spontaneous.