Solubility prediction of drugs in water-polyethylene glycol 400 mixtures using Jouyban-acree model

A numerical method is proposed for predicting solubility of drugs in water-PEG 400 mixtures based on the Jouyban-Acree cosolvency model. The accuracy of the proposed method is evaluated by computing mean percentage deviation (MPD) and compared with that of log-linear model of Yalkowsky. The overall MPDs of the Jouyban-Acree model and the most accurate version of Yalkowsky's model are 39.8 (+/-46.7) % and 175.8 (+/-266.4) %, respectively, and the mean difference is statistically significant (p < 0.0005). The proposed method produces acceptable residual distribution and the probability of solubility prediction with residual log of solubility <0.5 unit is 0.86. The applicability of the proposed method could be extended for predicting the solubility of drugs in water-PEG 400 mixtures at various temperatures. The impact of various log P values computed using different software is also studied and the results of ANOVA revealed that there are no significant differences between the accuracy of the predicted solubilities employing various log P values.     

Solubility prediction of paracetamol in binary and ternary solvent mixtures using Jouyban-Acree model

The Jouyban-Acree model has been used to predict the solubility of paracetamol in water-ethanol-propylene glycol binary and ternary mixtures based on model constants computed using a minimum number of solubility data of the solute in water-ethanol, water-propylene glycol and ethanol-propylene glycol binary mixtures. Three data points from each binary solvent system and solubilities in neat solvents were used to calculate the binary interaction parameters of the model. Then the solubility at other binary solvent compositions as well as in a number of ternary solvents were predicted, and the mean percentage deviation (+/-S.D.) of predicted values from experimental solubilities was 7.4(+/-6.1)%.     

Predicting solubility of anthracene in non-aqueous solvent mixtures using a combination of Jouyban-Acree and Abraham models

Quantitative structure property relationships were proposed to calculate the binary interaction terms of the Jouyban-Acree model using coefficients of Abraham solvational models. The applicability of the proposed methods for reproducing solubility data of anthracene in binary solvents has been evaluated using 56 solubility data sets collected from the literature. The mean percentage deviation (MPD) of experimental and calculated solubilities, using predicted mole fraction solubility of anthracene in solvents 1 and 2, has been computed as a measure of accuracy and the MPD of the proposed methods were 5.5 and 4.2%. The accuracy of the method was compared with that of a previously reported method where the MPD was 14.4% and the mean differences between proposed and previous methods was statistically significant. To provide a predictive model, solubility of anthracene was computed using Abraham solvational models and employed to predict the solubility in binary solvents using derived model constants of Jouyban-Acree model and the obtained MPDs were 37.9 and 22.2%, respectively.     

Solubilities of poly(ethylene glycol)s in the mixtures of supercritical carbon dioxide and cosolvent

The solubilities of poly(ethylene glycol) (PEG6000) (M.W.=7500) in the mixtures consisting of supercritical carbon dioxide (CO₂) and cosolvent have been measured by observing the cloud points at 313.15 K and 16 MPa. Ethanol and toluene were used as cosolvents. The solubility of PEG6000 is extremely low in either CO₂ or ethanol, but becomes about 20 wt.% in a mixture of the two. The maximum solubility is achieved at about 50 wt.% (polymer-free) ethanol. The solubilities of PEG6000 in the mixtures of supercritical CO₂ and the cosolvent have been correlated by a regular solution model using the local compositions of solvents around a solute molecule, and an expanded liquid equation of state model.     

Mathematical representation of solubility of electrolytes in binary solvent mixtures using Jouyban-Acree model

Applicability of a solution model for calculating salt's solubility in binary solvent mixtures was shown. The accuracy of the proposed model was evaluated by computing mean percentage deviation (MPD) employing available solubility data of electrolytes in binary solvents at various temperatures from the literature. The overall MPD (+/-S.D.) for correlation of solubility data was 4.7+/-5.1% and for prediction using model trained by a minimum number of experimental data points was 10.5+/-12.5%.     

Solubility of Acetaminophen and Ibuprofen in Polyethylene Glycol 600, N-Methyl Pyrrolidone and Water Mixtures

The solubility of acetaminophen and ibuprofen in binary and ternary mixtures of N-methyl pyrrolidone, polyethylene glycol 600 and water at 25 °C were determined and the solubilities are mathematically represented by the Jouyban–Acree model. The density of the solute-free solvent mixtures was measured and employed to train the Jouyban–Acree model and then the densities of the saturated solutions were predicted. The overall mean relative deviations (OMRDs) for fitting the solubility data of acetaminophen and ibuprofen in binary mixtures are 3.2% and 6.0%, respectively. The OMRDs for fitting the solubilities in ternary solvent mixtures for acetaminophen and ibuprofen are 15.0% and 28.6%, respectively, and the OMRD values for predicting all solubilities of acetaminophen and ibuprofen by a trained version of the Jouyban–Acree model are 9.4% and 17.8%, respectively. The prediction OMRD for the density of saturated solutions is 1.9%.     

Measurement and correlation of solubility of benzamide in supercritical carbon dioxide with and without cosolvent

The experimental equilibrium solubility of benzamide in supercritical carbon dioxide was measured at temperatures between 308 K and 328 K and for pressures from 11.0 MPa to 21.0 MPa using a dynamic flow method. The effects of three cosolvents - ethanol, acetone and ethylene glycol, were investigated at a cosolvent molar concentration of 3.5%. The results showed that the solubility was enhanced by the presence of the three cosolvents, and ethanol exhibited the highest cosolvent effect. The solubility data in the absence and presence of cosolvents were correlated by two density-based models. The calculated results showed satisfactory agreement with the experimental data.     

Calculation of the viscosity of binary liquids at various temperatures using Jouyban-Acree model

Applicability of the Jouyban-Acree model for calculating absolute viscosity of binary liquid mixtures with respect to temperature and mixture composition is proposed. The correlation ability of the model is evaluated by employing viscosity data of 143 various aqueous and non-aqueous liquid mixtures at various temperatures collected from the literature. The results show that the model is able to correlate the data with an overall percentage deviation (PD) of 1.9+/-2.5%. In order to test the prediction capability of the model, three experimental viscosities from the highest and lowest temperatures along with the viscosities of neat liquids at all temperatures have been employed to train the model, then the viscosity values at other mixture compositions and temperatures were predicted and the overall PD obtained is 2.6+/-4.0%.     

Solubility of bosentan in {propylene glycol + water} mixtures at various temperatures: experimental data and mathematical modelling

Solubility measurements were performed for bosentan (BST) in binary mixtures of propylene glycol (PG) and water at atmospheric pressure within the temperature range, T = 293.2 – 313.2 K by employing a shake-flask method. Generated solubility data were correlated with Jouyban-Acree-van’t Hoff model and the accuracies of the predicted solubilities and model performance were illustrated by mean relative deviations (MRD). Furthermore, the apparent thermodynamic properties of BST dissolving in all the mixed solvents were calculated, and the obtained results show that the dissolution process is endothermic. By using the inverse Kirkwood–Buff integrals, it was observed that BST is preferentially solvated by water in water-rich solvent mixtures and preferentially solvated by PG (as a cosolvent) in the composition range of 0.20 < x₁ < 1.00 at 298.2 K.     

Thermodynamics of Mixing and Solvation of Ibuprofen and Naproxen in Propylene Glycol + Water Cosolvent Mixtures

By using the van’t Hoff and Gibbs equations, solubility data of ibuprofen (IBP) and naproxen (NAP) determined at several temperatures in propylene glycol (PG) + water (W) cosolvent mixtures were used to evaluate the Gibbs energies, enthalpies, and entropies of solution, mixing and solvation. The solubilities are greater in pure PG and lower in W in both cases at all studied temperatures. These results clearly show that a cosolvent effect is present in these systems. The solvation of these drugs was greater in W compared to PG, and it was lower in the cosolvent mixtures compared with the pure solvents. By means of an enthalpy-entropy compensation analysis, non-linear ΔH _soln^o versus ΔG _soln^o compensation plots were obtained, with negative and positive slopes if all of the composition intervals are considered. Accordingly, it follows that at low PG solvent fractions the dominant factor for the solubility of IBP and NAP in this cosolvent system is the entropy, probably due to loosening of the water structure caused by the addition of the cosolvent.     

Solubilization of naproxen using N-methyl-2-pyrrolidone or ethanol and β-cyclodextrin

Solubility trend of naproxen in the presence of 5 and 10 mM of β-CD was measured at 298.2 K and compared with solubility profiles in the absence of β-CD for water + cosolvent mixtures. The saturated solutions of the given volume fractions were reached using shake-flask method, and then the solubility values were measured by UV spectrophotometric method at 256 nm. Afterwards, the experimental solubility data points of naproxen in water + ethanol (EtOH) and water + N-methyl-2-pyrrolidone with and without β-cyclodextrin (β-CD) were correlated with Jouyban–Acree model. Calculation results revealed that the back-calculated solubilities were in good agreement with the corresponding experimental values. By applying the correlated equations, one can rapidly predict the solubility of naproxen in all solvent compositions.     

Measurement and prediction of solubilities and diffusion coefficients of carbon dioxide in starch–water mixtures at elevated pressures

The solubility and diffusion coefficient of carbon dioxide in intermediate‐moisture starch–water mixtures were determined both experimentally and theoretically at elevated pressures up to 16 MPa at 50 °C. A high‐pressure decay sorption system was assembled to measure the equilibrium CO₂ mass uptake by the starch–water system. The experimentally measured solubilities accounted for the estimated swollen volume by Sanchez–Lacombe equation of state (S‐L EOS) were found to increase almost linearly with pressure, yielding 4.0 g CO₂/g starch–water system at 16 MPa. Moreover, CO₂ solubilities above 5 MPa displayed a solubility increase, which was not contributed by the water fraction in the starch–water mixture. The solubilities, however, showed no dependence on the degree of gelatinization (DG) of starch. The diffusion coefficient of CO₂ was found to increase with concentration of dissolved CO₂, which is pressure‐dependent, and decrease with increasing DG in the range of 50–100%. A free‐volume‐based diffusion model proposed by Areerat was employed to predict the CO₂ diffusivity in terms of pressure, temperature, and the concentration of dissolved CO₂. S‐L EOS was once more used to determine the specific free volume of the mixture system. The predicted diffusion coefficients showed to correlate well with the measured values for all starch–water mixtures. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 607–621, 2006     

Solubility Data of Diazepam in Binary and Ternary Mixtures of PEGs 200 and 400 with N-Methyl Pyrrolidone and Water at 298.2 K: Experimental Data and Modeling

Experimental solubilities of diazepam in binary and ternary solvents of polyethylene glycols 200 and 400 with N-methyl pyrrolidone and water at T = 298.2 K are reported. The Jouyban–Acree model was used to fit solubility data of diazepam in the binary and ternary solvent mixtures (106 data points) in which the overall mean relative deviations (OMRD %) is 13.1 % and the prediction OMRD % is 31.7 %. The combined version of the Jouyban–Acree model with Hansen solubility parameters was used for fitting and predicting the solubility data and the OMRDs % are 10.0 and 20.8 %, respectively. Also, the previously proposed trained versions of the Jouyban–Acree model were used for predicting the reported data in this work and all results are listed in the tables. The density of the solute-free solvent mixtures were measured and employed to calculate the constants of the Jouyban–Acree model and then the densities of the saturated solutions were predicted.     

A cosolvency model to predict solubility of drugs at several temperatures from a limited number of solubility measurements

A cosolvency model to predict the solubility of drugs at several temperatures was derived from the excess free energy model of Williams and Amidon. The solubility of oxolinic acid, an antibacterial drug, was measured in aqueous (water+ethanol) and non-aqueous (ethanol+ethyl acetate) mixtures at several temperatures (20, 30, 35, 40 degrees C). Oxolinic acid displays a solubility maximum in each solvent mixture at solubility parameter values of 32 and 22 MPa(1/2). The temperature and heat of fusion were determined from differential scanning calorimetry. The solvent mixtures do not produce any solid phase change during the solubility experiments. The experimental results and those from the literature were employed to examine the accuracy and prediction capability of the proposed model. An equation was obtained to represent the drug solubility changes with cosolvent concentration and temperature. The model was also tested using a small number of experimental solubilities at 20 and 40 degrees C showing reasonably accurate predictions. This is important in pharmaceutics because it save experiments that are often expensive and time consuming.     

Solubility prediction of deferiprone in N-methyl-2-pyrrolidone + ethanol mixtures at various temperatures using a minimum number of experimental data

Experimental solubility of deferiprone (DFP) in N-methyl-2-pyrrolidone (NMP) + ethanol (EtOH) mixtures at 293.2, 298.2, 303.2 and 308.2 K was determined and mathematically represented using various models. The trained versions of the van’t Hoff equation, its combined version with log-linear model, Jouyban–Acree model and a combination of van’t Hoff + Jouyban–Acree model were reported to simulate DFP solubility in the binary mixture compositions at various temperatures. The mean percentage deviation (MPD) was used as an accuracy criterion. The obtained overall MPDs for back-calculated and predicted solubility of DFP in NMP + EtOH mixtures varied from 1.1% to 3.2% and 2.6% to 6.6%, respectively. Some of apparent thermodynamic quantities for the dissolution processes of DFP are also reported.     

Determination and mathematical modelling of budesonide solubility in N-methyl-2-pyrrolidone + water mixtures from T = 293.2 to 313.2 K

The solubilities of budesonide (BDS) in binary aqueous mixtures of N-methyl-2-pyrrolidone at temperatures ranging from 293.2 to 313.2 K were determined and mathematically correlated by three cosolvency models, i.e. Jouyban–Acree model, Jouyban–Acree–van’t Hoff model and modified Wilson model. The solubilities were measured using the shake-flask method and the models wereused to fit the solubility data of BDS in the solvent mixtures. The obtained mean relative deviations (MRDs %) for cosolvency models trained using whole data points varied between 5.0% and 31.0%. Solubilities were also predicted by the generally trained version of the Jouyban–Acree model with the MRD of 37.0%. Furthermore, the apparent thermodynamic properties of dissolution process of BDS in all the mixed solvents were calculated according to van’t Hoff and Gibbs equations. Dissolution of BDS in these mixed solvents is an endothermic process.     

Total Solubility Determination of Mixtures Containing Ampicillin Anhydrate and Ampicillin Trihydrate

The dissolved concentrations of ampicillin anhydrate, ampicillin trihydrate, and their mixtures were experimentally determined. For 100% ampicillin anhydrate and 100% ampicillin trihydrate cases, the dissolved concentration (mg/mL) was equal to the total amount of 100% ampicillin anhydrate and 100% ampicillin trihydrate in 1 mL solution up to the solubility (10.8 mg/mL) of 100% ampicillin anhydrate and the solubility (5.4 mg/mL) of 100% ampicillin trihydrate. For an ampicillin anhydrate to ampicillin trihydrate mixture ratio of 75:25, the relationship between the dissolved concentration and the total amount of the mixture in 1 mL solution was the same as the 100% ampicillin anhydrate case. As for the ampicillin anhydrate to ampicillin trihydrate mixture ratios of 50:50 and 25:75, the total solubility of 10.8 mg/mL could be reached at greater amounts of the mixtures. A model of diffusion‐controlled dissolution rate mechanism with two experimental solubilities, 10.8 mg/mL for ampicillin anhydrate and 5.4 mg/mL for ampicillin trihydrate, was used to successfully interpret the solubility data.     

Equilibrium solubility,preferential solvation and apparent specific volume of sucrose in some {cosolvent (1) + water (2)} mixtures at 298.2 K

Sucrose is the most widely used sweetener in food and pharmaceuticals. Solubility data of this excipient in aqueous cosolvent mixtures is not abundant. Thus, the main objective of this research was to determine and correlate the equilibrium solubility of sucrose in some {cosolvent (1) + water (2)} mixtures at 298.2 K. Cosolvents were ethanol, propylene glycol and glycerol. Shaken flask method was used to determine isothermal solubility. Concentration measurements were performed by means of density determinations. Solubility of sucrose decreases non-linearly with the addition of cosolvent to water. By means of the inverse Kirkwood–Buff method it is shown that sucrose is preferentially solvated by cosolvent in water-rich mixtures but preferentially solvated by water in cosolvent-rich mixtures. Jouyban–Acree model correlates solubility values with the mixtures composition for all cosolvent systems. Moreover, apparent specific volume of sucrose was also calculated from density and compositions.     

Preferential solvation of some antiepileptic drugs in {cosolvent (1) + water (2)} mixtures at 298.15 K

The solubility of lamotrigine (LTG), clonazepam (CZP) and diazepam (DZP) in some {cosolvent (1) + water (2)} mixtures expressed in mole fraction at 298.15 K was calculated from reported solubility values expressed in molarity by using the densities of the saturated solutions. Aqueous binary mixtures of ethanol, propylene glycol and N-methyl-2-pyrrolidone were considered. From mole fraction solubilities and some thermodynamic properties of the solvent mixtures, the preferential solvation of these drugs by both solvents in the mixtures was analysed by using the inverse Kirkwood–Buff integrals. It is observed that LTG, CZP and DZP are preferentially solvated by water in water-rich mixtures in all the three binary systems analysed. In {ethanol (1) + water (2)} mixtures, preferential solvation by water is also observed in ethanol-rich mixtures. Nevertheless, in {propylene glycol (1) + water (2)} and {N-methyl-2-pyrrolidone (1) + water (2)} mixtures preferential solvation by the cosolvent was observed in cosolvent-rich mixtures.