Solubility prediction of paracetamol in water-ethanol-propylene glycol mixtures at 25 and 30 degrees C using practical approaches

The solubility of paracetamol in water-ethanol-propylene glycol binary and ternary mixtures at 25 and 30 degrees C was determined using flask shake method. The generated data extended the solubility database for further computational investigations and also was used to assess the prediction capability of the Jouyban-Acree model. A new version of the model was proposed for modeling the solubility data in water-cosolvent mixtures with the cosolvent concentration of <50% which is required in pharmaceutical formulations. The accuracy of the predicted solubilities was evaluated by the mean percentage deviation (MPD) between the predicted and experimental solubilities. The overall MPD of the Jouyban-Acree model and the log-linear model of Yalkowsky for the entire composition range of the cosolvents were 11.0+/-8.7 and 55.4+/-17.8%, respectively; the corresponding values for the predicted solubilities in mixtures having a cosolvent concentration of <50% were 12.0+/-9.1 and 22.0+/-11.0%.     

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)%.     

Surface tension calculation of mixed solvents with respect to solvent composition and temperature by using Jouyban-Acree model

Applicability of a solution model, i.e. Jouyban-Acree model (JAM), for calculating surface tension of binary and ternary solvents at various temperatures has been shown employing experimental surface tension data collected from the literature. The accuracy of the model was evaluated by calculating average percentage deviation (APD) between calculated and observed values. The obtained overall APD (+/-S.D.) for JAM using binary solvent data were 4.06 (+/-4.27) and 8.07 (+/-9.78)%, respectively for correlative and predictive analyses. The corresponding values for the best similar model from the literature were 8.86 (+/-6.40) and 37.10 (+/-27.65)% and the mean APD differences between JAM and previously published model were significant (p<0.003). The capability of JAM for correlating surface tension of ternary solvents at various temperatures was also shown and the overall APD was 1.39 (+/-0.37)%.     

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.     

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%.     

Naproxen solubility in binary and ternary solvents of polyethylene glycols 200, 400 or 600 with ethanol and water at 298.2 K – experimental data report and modelling

The solubilities of naproxen in the binary and ternary mixtures of polyethylene glycols 200, 400 or 600 with ethanol and water (185 data points) at 298.2 K are determined and mathematically represented by cosolvency models. The obtained overall mean relative deviations (OMRDs) for fitting the solubility data of naproxen in binary and ternary mixtures using Williams–Amidon and Jouyban–Acree model are 15.7% and 16.5%, respectively, and the OMRD values for predicting the solubility data of naproxen by the trained versions of Williams–Amison and Jouyban–Acree models are 71.1% and 64.4%, respectively.     

Estimation of aqueous solubility of organic molecules by the group contribution approach. Application to the study of biodegradation.

A reliable and generally applicable aqueous solubility estimation method for organic compounds based on a group contribution approach has been developed. Two models have been established based on two different sets of parameters. One has a higher accuracy, while the other has a more general applicability. The prediction potentials of these two models have been evaluated through cross-validation experiments. For model I, the mean cross-validated r2 and SD for 10 such cross-validation experiments were 0.946 and 0.503 log units, respectively. While for model II, they were 0.953 and 0.546 log units, respectively. Applying our models to estimate the water solubility values for the compounds in an independent test set, we found that model I can be applied to 13 out of 21 compounds with a SD equal to 0.58 log unit and model II can be applied to all the 21 compounds with a SD equal to 1.25 log units. Our models compare favorably to all the current available water estimation methods. A program based on this approach has been written in FORTRAN77 and is currently running on a VAX/VMS system. The program can be applied to estimate the water solubility of the water solubility of any organic chemical with a good or fairly good accuracy except for except for electrolytes. Applying our aqueous solubility estimation models to biodegradation studies, we found that although the water solubility was not the sole factor controlling the rate of biodegradation, ring compounds with greater solubilities were more likely to biodegrade at a faster rate. The significance of the relationship between water solubility and biodegradation activity has been illustrated by predicting the biodegradation activity of 27 new chemicals based solely on their estimated solubility values.     

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 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.     

Solubility of Ketoconazole in Binary and Ternary Solvents of Polyethylene Glycols 200, 400 or 600 with Ethanol and Water at 298.2 K. Data Report and Analysis

The solubilities of ketoconazole in binary and ternary mixtures of water, ethanol and polyethylene glycols 200, 400 or 600 (185 data points) were determined at 298.2 K. Williams–Amidon and Jouyban–Acree cosolvency models were used to model the data, with overall mean relative deviations (OMRDs) for the solubility data in binary and ternary solvents of 17.5 and 23.5%, respectively. For predicting the solubility data of ketoconazole the trained versions of the models were used and the OMRD values were 47.7 and 33.0%, respectively.     

SLIPPER-2001 -- software for predicting molecular properties on the basis of physicochemical descriptors and structural similarity

A new approach for predicting the lipophilicity (log P), solubility (log Sw), and oral absorption of drugs in humans (FA) is described. It is based on structural and physicochemical similarity and is realized in the software program SLIPPER-2001. Calculated and experimental values of log P, log Sw, and FA for 42 drugs were used to demonstrate the predictive power of the program. Reliable results were obtained for simple compounds, for complex chemicals, and for drugs. Thus, the principle of "similar compounds display similar properties" together with estimating incremental changes in properties by using differences in physicochemical parameters results in "structure - property " predictive models even in the absence of a precise understanding of the mechanisms involved.     

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.     

Prediction of solubility of drugs by conductor-like screening model for real solvents

The solubility of drugs in solvents is fundamentally important for drug development and manufacturing. As the experimental measurements of the solubility are extremely laborious tasks, reliable prediction methods are highly required. We have employed the conductor-like screening model for real solvents (COSMO-RS) in predicting the solubility of drugs and drug-like compounds in various solvent systems. We also evaluated the salt effect on the solubility of caffeine using this method. The present results demonstrated that COSMO-RS has reasonably reproduced the experimental data and have proved that this method is generally available in predicting the solubility of drugs.     

Multiple solubility maxima of oxolinic acid in mixed solvents and a new extension of Hildebrand solubility approach

A new extension of the Hildebrand solubility approach which describes drug solubility in solvent mixtures showing multiple solubility peaks, the chameleonic effect, is proposed. The experimental solubilities of oxolinic acid were measured at 25 degrees C in solvent mixtures of ethanol-water and ethanol-ethyl acetate. A plot of the mole fraction of the drug against the solubility parameter (delta) of the solvent mixtures displays two peaks at delta = 30.78 MPa1/2 (80% v/v of ethanol in water) and at delta = 20.90 MPa1/2 (30% v/v of ethanol in ethyl acetate). The new extension proposed reproduces two solubility peaks. The thermograms of the solid phase before and after equilibration with the solvent mixtures did not show significant changes. The new extension was also tested with experimental data previously reported for drugs showing two solubility peaks of different height. The accuracy of other published models for describing two solubility maxima is also compared.     

氯代苯、醇、酯气相色谱保留指数与其正辛醇-水分配系数相关性

报道了氯代苯、醇、酯类化合物气相色谱保留指数与其正辛醇－水分配系数的相关性，研究了固定相极性对相关性影响，得出弱极性柱上测得的化合物保留指数能更准确地预测其分配系数，从而为极性化合物氯代苯、醇、酯分配系数的测定和预测提供了一种简便易行的新方法。     

Models to predict solubility in ternary solvents based on sub-binary experimental data

The capability of the extended forms, of two well established cosolvency models, i.e. the combined nearly ideal binary solvent/Redlich-Kister equation and the modified Wilson model, used to predict the solute solubility in non-aqueous ternary solvent mixtures is presented. These predictions are based on the measured solubilities of anthracene in binary solvent mixtures. As a result the values of average percent deviations were less than 2% for the anthracene solubility in ternary mixtures. This work was also extended to other cosolvency models, ie. the extended Hildebrand solubility approach and the mixture response surface method, which are also commonly used for correlating solubility data in ternary solvents. The accuracy of the models is compared with each other and also with a published solubility model for ternary mixtures. The results illustrate that all models produced comparable accuracy.     

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%.     

Solubility of anthracene in binary alcohol + 1-pentanol solvent mixtures at 25°C: Comparison of expressions derived from Mobile Order theory and the Kretschmer-Wiebe association model

A relatively simple expression is developed for predicting the solubility of an inert crystalline solute in binary alcohol + alcohol solvent mixtures based upon the Kretschmer-Wiebe association model. The predictive accuracy of the newlyderived expression is compared to equation(s) derived previously from Mobile Order theory using experimental anthracene solubilities in seven binary alcohol + 1-pentanol solvent mixtures at 25°C, which were measured as part of the present investigation. Computations show that both models accurately describe the solubility behavior of anthracene in the binary solvent systems studied. Average absolute deviations between observed and predicted values were 0.9% and 1.4% for the Kretschmer-Wiebe and Mobile Order predictive equations, respectively.     

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.