Apparent Thermodynamic Analysis Research Articles

The dissolution behavior and apparent thermodynamic analysis of propacetamol hydrochloride in pure and mixed solvents

In order to study the solubility of the formed solute in the reaction solvent, the solubility of propacetamol hydrochloride (PRO) in pure and mixed solvents was experimentally determined at T = 273.15–313.15 K. In all selected pure solvents, the solubility data form high to low was followed by the sequence: methanol > ethanol > acetone > n-propanol > isopropanol > acetonitrile. In mixture of (acetone + ethanol), the solubility decreased monotonically with the increasing mass fraction of acetone in mixed solvents at a certain temperature. The properties of solvents and the interaction between solvents and solutes were analyzed. All RAD values in the modified Apelblat equation are less than those in λh equation. Therefore, modified Apelblat is more suitable for correlating the solubility data of PRO in selected pure solvents. In addition, satisfactory correlation results in (acetone + ethanol) were obtained by Jouyban-Acree model. The values of ΔH°sol and ΔS°sol are all positive in this experiment, which indicates the dissolution process is not only endothermic but also entropy-driving. Moreover, the values of %ξH are greater than those of %ξTS, which indicates the enthalpy is the main contributor to the change of standard Gibbs energy during the dissolution process of PRO.

Solubility of sulfacetamide in aqueous propylene glycol mixtures: Measurement, correlation, dissolution thermodynamics, preferential solvation and solute volumetric contribution at saturation

The equilibrium solubility at temperatures from (278.15 to 318.15) K, dissolution thermodynamics, preferential solvation, and apparent specific volume at saturation of sulfacetamide (SCM) in {propylene glycol (PG) (1) + water (2)} mixtures is reported. Mole fraction solubility of SCM (x3) increases when temperature arises and also increases with the PG proportion arising. Solubility behavior was adequately correlated and/or predicted by the Jouyban-Acree and Jouyban-Acree-van't Hoff models and the obtained mean percentage deviations (MPD) are varied between 6.5 and 11.5%. 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 SCM is preferentially solvated by water molecules in water-rich mixtures but preferentially solvated by PG in the other mixtures. Further, the apparent specific volumes of SCM at saturation were also calculated.

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

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.

Apparent thermodynamic analysis and the dissolution behavior of levamisole hydrochloride in three binary solvent mixtures

The solubility of levamisole hydrochloride (LH) in binary {methanol (MT) + ethanol (EA), methanol (MT) + 2-propanol (IPA)} solvent mixtures from 283.15 K to 323.15 K and dimethyl sulfoxide (DMSO) + ethanol (EA) from 293.15 K to 333.15 K were obtained under the pressure of 0.1MPa by using a dynamic method. Moreover, the experimental solubility results of LH in this work were correlated well with five thermodynamic models namely “Yaws model, van’t Hoff model, Universal Quasi-Chemical (UNIQUAC) model, non-random two liquid (NRTL) model and general single (GSM) model”. The minimum RMSD and ARD are 0.0064 and 0.17 respectively and they are both calculated with the GSM model. Besides, the apparent thermodynamic properties of LH in the selected binary solvent mixtures were discussed. Analysis results showed that enthalpy-favored mechanism plays a major role in the dissolution process of LH.

Improving the solubility of temozolomide by cosolvent and its correlation with the Jouyban-Acree and CNIBS/R-K models

In recent years, the number of insoluble drug candidates has increased, with almost 70% of new drug candidates showing poor solubility. Cosolvent was used in this work to improve the solubility of poorly soluble temozolomide. The solubility data of temozolomide in four mixed solvents including (ethyl acetate + methanol), (ethyl acetate + ethanol), (ethyl acetate + n-propanol) and (ethyl acetate + isopropanol) at temperatures from 273.15 to 318.15 K were determined and evaluated by Jouyban-Acree model and CNIBS/R-K model. In mixtures of (ethyl acetate + methanol) and (ethyl acetate + ethanol) and at a certain temperature, the values increase with increasing cosolvent (ethyl acetate) mass fraction w to a maximum at w = 0.6 and then decrease, while it increases to a maximum at w = 0.8 in (ethyl acetate + n-propanol) and (ethyl acetate + isopropanol). Particularly, the effect of cosolvent on the dissolution process of temozolomide is an important aspect of its recrystallization and purification. All the values of RMSD and RAD are no more than 3.77 × 10−2 and 2.2 × 10−5, respectively. It shows that both thermodynamic models can be used to correlate solubility data of objective compound. Moreover, the results of apparent thermodynamic analysis indicate that the dissolution is a favorable, endothermic and entropy driven process.

The dissolution behaviour and apparent thermodynamic analysis of diprophylline in pure and mixed solvents

Co-solvent plays an important role in drug crystallization. More importantly, the change of temperature and the addition of co-solvent can make the operation of crystallization purification more controllable. In this work, the solubility of diprophylline in methanol, ethanol, n-propanol, isopropanol, acetone, acetonitrile, ethyl acetate, 1,4-dioxane, water, toluene and mixture of (methanol + water) was experimentally determined at T = 283.15–323.15 K. The solubility data obtained experimentally in all studied pure solvents followed the sequence: water > 1,4-dioxane > methanol > acetonitrile > isopropanol > ethanol > n-propanol > ethyl acetate > toluene > acetone. In addition, in mixture of (methanol + water) the solubility increases at first and then decreases with the increasing mass fraction of methanol. The composition dependence of the solubility has a maximum around (methanol mass fraction) w = 0.4 at all investigated temperatures. Moreover, the effect of solvent properties on solubility is briefly discussed. The modified Apelblat equation, λh equation, Jouyban-Acree model and CNIBS/R-K model are applied to correlate the solubility. All the values of RAD and RMSD are no more than 5.34 × 10−2 and 5.83 × 10−4, respectively. Apparent thermodynamic analysis indicates that the dissolution is an endothermic and entropy driven process.

Thermodynamic solubility and solvation behavior of ferulic acid in different (PEG-400 + water) binary solvent mixtures

This work was carried out to determine solubility, solution thermodynamics, solvation behavior, and molecular interactions of a natural compound ferulic acid (FLA) in different ‘[polyethylene glycol-400 (PEG-400) + water]’ binary solvent mixtures at ‘T = 298.2 K to 318.2 K’ and ‘p = 0.1 MPa.’ The mole fraction solubilities (xe) of FLA were determined by liquid chromatographic technique using a static equilibrium technique. The obtained solubility data of FLA were regressed using ‘Van’t Hoff, Apelblat, Yalkowsky-Roseman and Jouyban-Acree models.’ The solubility of FLA (expressed in mole fraction) was enhanced with elevation in absolute temperature in each ‘PEG-400 + water’ binary solvent mixture evaluated. The maximum xe values of FLA were recorded in neat PEG-400 (1.94 × 10−1) at ‘T = 318.2 K.’ While, the minimum one was obtained in neat water (4.90 × 10−5) at ‘T = 298.2 K.’ The molecular interactions between FLA-PEG-400 and FLA-water were obtained by determination of activity coefficients of FLA in different ‘PEG-400 + water’ binary solvent mixtures. The physical data of activity coefficients recorded in this work suggested strong molecular interactions in FLA-PEG-400 in comparison with FLA-water. ‘Apparent thermodynamic analysis’ suggested an ‘endothermic and entropy-driven dissolution’ of FLA in each ‘PEG-400 + water’ binary solvent mixture investigated.

Solubility of sulfacetamide in (ethanol + water) mixtures: Measurement, correlation, thermodynamics, preferential solvation and volumetric contribution at saturation

The equilibrium solubility at temperatures from (278.15 to 313.15) K, dissolution thermodynamics, preferential solvation, and apparent specific volume at saturation of sulfacetamide (SCM) in {ethanol (1) + water (2)} mixtures is reported. Mole fraction solubility of SCM (x3) increases when temperature arises and also increases with the ethanol proportion increasing reaching maximum values in the mixture w1 = 0.80. It varies from 7.06 × 10−4 in neat water to 2.506 × 10−2 in the mixture w1 = 0.80 at 298.15 K. Solubility behavior was adequately correlated by various cosolvency models and the obtained mean percentage deviations (MPD) varied between 2.6 and 15.9%. Moreover, the trained Jouyban-Acree model using a minimum number of 7 data points is used for predicting the rest of data points with the MPD of ~14% (N = 81). In addition, the generally trained model (Jouyban-Acree-Abraham) was also used to predict the solubility data of SCM in {ethanol (1) + water (2)} mixtures and obtained MPD for prediction was 36.9%. From the variation of solubility with temperature the apparent thermodynamic analysis of dissolution was performed in all the mixtures and neat solvents. Based on the inverse Kirkwood-Buff integrals (IKBI) preferential solvation parameters were calculated. SCM is preferentially solvated by water molecules in water-rich mixtures and also in ethanol-rich mixtures. Further, from densities of the saturated solutions and those of the cosolvent mixtures free of drug, the apparent specific volumes at saturation were also calculated.

Solubility measurement, Hansen solubility parameters and solution thermodynamics of gemfibrozil in different pharmaceutically used solvents

Gemfibrozil (GEM) is cholesterol-lowering agent which is being proposed as poorly water soluble drug (PWSD). Temperature based solubility values of GEM are not yet available in literature or any pharmacopoeia/monograph. Hence, the present studies were carried out to determine the solubility of PWSD GEM (as mole fraction) in various pharmaceutically used solvents such as water (H2O), methanol (MeOH), ethanol (EtOH), isopropanol (IPA), 1-butanol (1-BuOH), 2-butanol (2-BuOH), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), dimethyl sulfoxide (DMSO) and Transcutol® (THP) at the temperatures ranging from T = 298.2 K–318.2 K under atmospheric pressure P = 0.1 MPa. Equilibrium/experimental solubilities of GEM were recorded by applying a saturation shake flask methodology and regressed using ‘van’t Hoff and Apelblat models’. Hansen solubility parameters for GEM and various pharmaceutically used solvents were estimated using HSPiP software. The solid states of GEM (both in pure and equilibrated states) were studied by ‘Differential Scanning Calorimetry’ which confirmed no transformation of GEM after equilibrium. Experimental solubilities of GEM in mole fraction were observed maximum in THP (1.81 × 10−1) followed by DMSO, PEG-400, EA, 1-BuOH, 2-BuOH, IPA, EtOH, PG, MeOH, EG and H2O (3.24 × 10−6) at T = 318.2 K and similar tendencies were also recorded at T = 298.2 K, T = 303.2 K, T = 308.2 K and T = 313.2 K. ‘Apparent thermodynamic analysis’ on experimental solubilities furnished ‘endothermic and entropy-driven dissolution’ of GEM in each pharmaceutically used solvent.

Measurement and correlation of solubility of ethylparaben in pure and binary solvents and thermodynamic properties of solution

Solubility data of bioactive compound such as ethylparaben (EtP) are important for the scientific and community. Therefore, in present study, solubility, solution thermodynamics and solute-solvent interactions (at molecular level) of EtP in nine cosolvent mixtures (1-propanol {n-PrOH) (1) + methanol (MeOH) (2)} including pure solvent (methanol and 1-propanol) at three different temperatures, i.e. (T =283.2 K, 298.2 K, and 313.2 K) and constant pressure (p = 0.1 MPa) were studied. Experimental solubility of EtP (expressed in mole fraction) was observed highest in n-PrOH at 313.2 K, so, mole fraction solubility of EtP (x3) increases when temperature arises and increases with n-PrOH proportion increasing. Ideal solubilities of EtP were estimated using their thermal parameters at three different temperatures. Ideal solubilities of EtP were observed similar to experimental solubilities of EtP at each temperature. With the help of ideal solubilities of EtP, activity coefficients were estimated. Based on estimated values of activity coefficients, highest interactions at molecular level were observed in rich-MeOH mixtures. Apparent thermodynamic analysis data showed endothermic and enthalpy-driven dissolution of EtP in each solvent and mixture studied. Solubility behavior was adequately correlated by means of the van’t Hoff and Yalkowsky-Roseman models combined.

Cosolvent effect on solubility of aripiprazole in mixed solvents and apparent thermodynamic analysis of dissolution process

Due to different polymorphs demonstrate significant variations in the drug properties such as solubility, stability and dissolution rate. In this work, we study the shape of the solubility profile of form X0 (the thermodynamically stable form at room temperature) in two mixtures of (n-propanol + acetone) and (isopropanol + acetone) at T = 278.15–318.15 K. The solubility value is a function of temperature and solvent composition. It increases at first and then decreases with the increasing concentration of acetone in mass fraction, and the composition dependence of the solubility has a maximum around mass fraction of acetone w = 0.6 at all investigated temperatures. The Jouyban-Acree model and CNIBS/R-K model are applied to correlate the solubility, and CNIBS/R-K model is more suitable. The values of dissolution standard Gibbs energy (ΔGsolo) and dissolution standard entropy (ΔSsolo) are all positive which indicate that the dissolution is not only endothermic but also entropy-driving.

Solubility of sulphadiazine in (acetonitrile + water) mixtures: measurement, correlation, thermodynamics and preferential solvation

ABSTRACTThe equilibrium solubility at temperatures from (293.15 to 313.15) K, dissolution thermodynamics and preferential solvation of sulphadiazine (SD) in {acetonitrile (ACN) (1) + water (2)} mixtures is reported. Mole fraction solubility of SD (x3) increases when temperature arises and also increases with the ACN proportion increasing. It varies from 4.81 × 10–6 in neat water to 6.02 × 10–4 in neat ACN at 298.15 K. Solubility behaviour was adequately correlated by Jouyban-Acree, modified Wilson and non-linear (proposed by Machatha et al.) models and the obtained mean percentage deviations (MPD) are 4.1%, 2.3% and 2.3%, respectively. The comparison of the MPD shows that the prediction using Jouyban-Acree model is more accurate than Jouyban-Acree-Abraham equation for solubility prediction of SD in {ACN (1) + water (2)}. From the variation of solubility with temperature the apparent thermodynamic analysis of dissolution was performed in all the mixtures and neat solvents. Based on the inverse Kirkwood-Buff integrals preferential solvation parameters were calculated. SD is preferentially solvated by water in water-rich mixtures (0.00 < x1 < 0.26) but preferentially solvated by ACN in the interval (0.26 < x1 < 0.65). In ACN-rich mixtures the behaviour is not well defined.

Measurement and Correlation of the Solubility of β-Cyclodextrin in Different Solutions at Different Temperatures and Thermodynamic Study of the Dissolution Process

A new improved formulation was studied to improve the rehydration properties of freeze-dried dumplings. To provide basic data for industrial applications, the solubility capabilities of β-Cyclodextrin in sucrose, NaCl, and a mixed solution were measured at temperatures ranging from 303.15 to 353.15 K using a laser monitoring method. The experimental values indicated that the solubility of β-Cyclodextrin in solvents increased with increasing temperature. The simplified Apelblat model, Apelblat model, and λh model were employed to analyze the experimental results using correlation tests. The relative average deviation (RAD) values between the experimental and calculated values were less than 0.095, 0.075, and 0.103 for the simplified Apelblat equation, Apelblat equation, and λh equation, respectively. Apparent thermodynamic analysis of β-Cyclodextrin dissolution was also performed at the mean temperature using the model parameters of Apelblat equation. Furthermore, thermodynamic properties of the solution process, including the enthalpy, entropy, and Gibbs free energy, were also calculated and analyzed. This study provides the basic data for applications in industrial production, and is specifically of great significance for the improved formulation of freeze-dried dumplings.

The dissolution behavior and apparent thermodynamic analysis of temozolomide in pure and mixed solvents

In commonly used solvents, the dissolving capacity of temozolomide is limited. This work is to research the dissolution behavior in different polarity ranges. The solubility of temozolomide in methanol, ethanol, n-propanol, isopropanol, acetone, acetonitrile, N,N-dimethylformamide (DMF), ethyl acetate, dimethyl sulfoxide (DMSO), 1,4-dioxane and mixture of (DMF + ethanol) was experimentally determined at T = 293.15–333.15 K. The modified Apelblat equation, λh equation, Jouyban-Acree model and CNIBS/R-K model are applied to correlate the solubility. All the values of RAD and RMSD are no more than 3.43 × 10−2 and 2.86 × 10−4, respectively. Apparent thermodynamic analysis indicate that the dissolution is an endothermic, spontaneous and entropy driven process. More importantly, the change of temperature and the addition of co-solvent (DMF) can make the operation of crystallization purification more controllable.

Solubility, solubility parameters and solution thermodynamics of thymoquinone in different mono solvents

Solubility data of bioactive compound such as thymoquinone (THQ) are scarce in research community. Therefore, in present study, solubility, solubility parameters, solution thermodynamics and solute-solvent interactions (at molecular level) of THQ in eleven mono solvents including “water (H2O), propylene glycol (PG), polyethylene glycol-400 (PEG-400), methanol (MeOH), ethanol (EtOH), isopropanol (IPA), 1-butanol (1-BuOH), 2-butanol (2-BuOH), ethyl acetate (EA), dimethyl sulfoxide (DMSO) and Transcutol® (THP)” at five different temperatures i.e. “T = 298.2 K, 303.2 K, 308.2 K, 313.2 K and 318.2 K” and constant pressure “p = 0.1 MPa” were studied. The characterization of solid phases of THQ suggested no transformation of THQ into polymorphs/solvates. Measured solubility data of THQ was regressed by “van't Hoff and Apelblat models” with overall deviations of 1.00 and 0.56%, respectively. Experimental solubilities of THQ (expressed in mole fraction) were recorded highest in THP followed by 2-BuOH, 1-BuOH, IPA, PEG-400, EA, DMSO, EtOH, MeOH, PG and H2O at “T = 318.2 K”. Same tendencies were also recorded at each temperature point studied. Ideal/theoretical solubilities of THQ were estimated using its thermal parameters at five different temperatures. Ideal solubilities of THQ were recorded much higher than experimental solubilities of THQ at each temperature. With the help of ideal solubilities of THQ, activity coefficients were estimated. Based on estimated values of activity coefficients, highest interactions at molecular level were recorded in THQ-THP. “Apparent thermodynamic analysis” data showed “endothermic and entropy-driven dissolution” of THQ in each mono solvent studied.

Solubility of citalopram hydrobromide in(ethanol + toluene) and (ethanol + ethyl acetate) at 283.15–318.15 K and its correlation with the Jouyban-Acree and CNIBS/R-K models

The solubility of citalopram hydrobromide in ethanol mixed with cosolvent toluene and ethyl acetate was measured at temperatures from 283.15 to 318.15 K to study the solubility improvement of the poorly soluble drug. The solubility increases with increasing cosolvent mass fraction w to a maximum value at w = 0.6 and then decreases. The Jouyban-Acree model and CNIBS/R-K model are applied to correlate the solubility. All the values of RMSD and RAD are no more than 5.36 × 10−2 and 5.72 × 10−4, respectively. Apparent thermodynamic analysis indicate that the dissolution is an endothermic, spontaneous and entropy driven process. More importantly, the effect of cosolvent on the dissolution process for citalopram hydrobromide is an important aspect of its purification, recrystallization and clinical application.

Solubility behavior, dissolution thermodynamics and solute–solvent intermolecular interactions of a solid antioxidant product in water + isopropanol liquid mixtures from 298.15 to 320.15 K

The solid–liquid equilibria of a poorly water-soluble antioxidant agent namely naringoside were assayed to determine solubility in binary liquid mixtures of water + isopropanol (iso-PrOH) between 298.15 K and 320.15 K under atmospheric pressure. The mole fraction solubilities of naringoside in the saturated solution were determined using a combination of static shake-flask and ultraviolet spectrophotometry techniques. The dissolution behavior of naringoside was correlated with three solution models consisting of the van’t Hoff equation, the modified Apelblat equation and the Buchowski-Ksiazczak λH equation. The modified Apelblat equation was more consistent than the two other correlation models. Apparent thermodynamic analysis of naringoside dissolution was also performed at the mean harmonic temperature using the model parameters of the modified Apelblat equation. Furthermore, the Kamlet, Abboud and Taft Linear Solvation Energy Relationship (KAT-LSER) model was applied to analyze the effect of the solute–solvent intermolecular interactions on the solubility of this natural bioactive product.

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.

Solubility determination of raloxifene hydrochloride in ten pure solvents at various temperatures: Thermodynamics-based analysis and solute–solvent interactions

The purpose of the present study was to determine the solubility of raloxifene hydrochloride (RHCl) in ten solvents: water, ethanol, isopropyl alcohol (IPA), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), Transcutol, 1-butanol, dimethyl sulfoxide (DMSO), and ethyl acetate (EA) at temperatures of 298.2–323.2 K and a pressure of 0.1 MPa. The solubility data obtained was fitted upon “Apelblat and Van't Hoff” equations. The maximum mole fraction solubility of RHCl was obtained in DMSO (5.02 × 10−2 at 323.2 K), followed by PEG-400 (5.92 × 10−3 at 323.2 K), EA (3.11 × 10−3 at 323.2 K), Transcutol (1.22 × 10−3 at 323.2 K), PG (2.19 × 10−4 at 323.2 K), 1-butanol (1.96 × 10−4 at 323.2 K), IPA (1.47 × 10−4 at 323.2 K), ethanol (7.90 × 10−5 at 323.2 K), EG (6.65 × 10−5 at 323.2 K), and water (3.60 × 10−5 at 323.2 K). Similar fashions were noticed at each studied temperature. The higher solubility of RHCl in DMSO, PEG-400, EA, and Transcutol was possibly referable to their lower polarity in comparison with water. The molecular interactions between the solute and solvent molecules were estimated by calculating parameters like activity coefficients, and more prominent solute–solvent molecular interactions were noted for RHCl–DMSO, RHCl–EA, and RHCl–PEG-400 in comparison with the other solute–solvent combinations. The outcomes of the “apparent thermodynamic analysis” showed that the dissolution of RHCl was “endothermic, spontaneous and entropy-driven” in all investigated solvents. The obtained solubility data of RHCl in commonly used solvents could be useful in the purification, recrystallization, and dosage form design of the drug.

Solubility determination and thermodynamic data of apigenin in binary {Transcutol® + water} mixtures

Solubility and thermodynamic data of apigenin (APG) in binary {2-(2-ethoxyethoxy)ethanol (Transcutol®) + water} mixtures were obtained in this work. The mole fraction solubilities (xe) of APG in binary {Transcutol® + water} mixtures were measured at temperature T = 298.15 K to318.15 K and atmospheric pressure p = 0.1 MPa. Solubility values of APG determined in this study were fitted well with four different computational models namely “van’t Hoff, Apelblat, Yalkowsky and Jouyban-Acree” models with root mean square deviations of <4.0%. The maximum xe value of APG was recorded in neat Transcutol® (0.382 at T = 318.15 K). However, the minimum xe value of APG was recorded in neat water (1.01 × 10−6 at T = 298.15 K). The values of activity coefficients were also determined for the evaluation of solute-solvent molecular interactions and results suggested higher solute-solvent molecular interaction in APG-Transcutol in comparison with other combinations studied. Apparent thermodynamic analysis suggested endothermic and entropy-driven dissolution of APG in all binary {Transcutol® + water} mixtures studied. Enthalpy-entropy compensation analysis suggested enthalpy-driven mechanism as the main mechanism for solvation behavior of APG.