Prediction of drug solubility in water-propylene glycol mixtures using Jouyban-Acree model

A trained version of the Jouyban-Acree model was presented to predict drug solubility in water-propylene glycol mixtures at various temperatures. The model is able to predict the solubility in various solubility units and requires the experimental solubility of a solute in mono-solvent systems. The mean percentage deviation (MPD) of predicted solubilities was computed to show the accuracy of the predicted data and 24% was found as the average MPD for 27 data sets studied. The proposed model enables the researchers to predict solubiliy in water-propylene glycol mixtures at various temperatures and reduces the number of required experimental data from five to two points.     

In silico prediction of drug solubility in water-dioxane mixtures using the Jouyban-Acree model

A numerical method based on the Jouyban-Acree model was presented for prediction of drug solubility in water-dioxane mixtures at various temperatures. The method requires drug solubility in monosolvent systems, i.e. two data points for each temperature of interest. The mean percentage deviation (MPD) of predicted solubilities was calculated to show the accuracy of the predicted data and 27% was found as the average MPD for 36 data sets studied. The proposed numerical method reduced the number of required experimental data from five to two points and could also be extended to predict solubility at various temperatures.     

Solubility and phase separation of benzocaine and salicylic acid in 1,4-dioxane-water mixtures at several temperatures

The solubilities of benzocaine and salicylic acid were determined in water-dioxane mixtures at several temperatures (5-40 degrees C for benzocaine and 10-40 degrees C for salicylic acid). The solubility curves as a function of dioxane ratio showed a maximum at 90% dioxane at all temperatures. Above 25 degrees C, the homogeneous mixture splits into two liquid immiscible phases. For benzocaine, the initial dioxane concentration range at which phase separation takes place increased with temperature (50-60% at 25 degrees C, 50-70% at 30-35 degrees C and 40-70% at 40 degrees C). For salicylic acid, the dioxane concentration required for phase separation (40-60% dioxane) did not change with temperature. Phase separation was not related to solid phase changes (polymorphism or solvates). The phase composition and drug extraction at the drug-rich phase were determined. The apparent enthalpies of the solution process were a nonlinear function of the dioxane ratio for both drugs. The apparent enthalpy of solution of benzocaine was larger than that expected at the upper limit of phase separation (70% dioxane), whereas for salicylic acid the apparent enthalpy of solution decreased abruptly at the region corresponding to phase separation (40-70% dioxane). Both drugs showed a nonlinear pattern of enthalpy-entropy compensation.     

Mathematical representation of solubility of amino acids in binary aqueous-organic solvent mixtures at various temperatures using the Jouyban-Acree model

Applicability of a solution model for calculating solubility of amino acids in binary aqueous-organic solvent mixtures at various temperatures was shown. The accuracy of the proposed model was evaluated by computing mean percentage deviation (MPD) employing available solubility data of amino acids in binary solvents at various temperatures from the literature. The overall MPD (+/- SD) for correlation of solubility data was 16.5 +/- 8.8%. In addition, the equations calculating solubility of amino acids in binary solvent mixtures at a fixed temperature was revisited.     

Solubility prediction of solutes in aqueous mixtures of ethylene glycols

The applicability of a trained version of the Jouyban-Acree model, for predicting the solubility of solutes in aqueous mixtures of ethylene glycol and its polymerized forms was shown. The solubilities of 8 drugs in binary mixtures were determined and the mean percentage deviation (MPD) was calculated as a prediction accuracy criterion and the overall MPD (+/- SD) was 23.2 (+/- 13.1)%.     

Deviations of drug solubility in water-cosolvent mixtures from the Jouyban-Acree model--effect of solute structure

Deviations of the predicted solubilities using the Jouyban-Acree model from experimental data were correlated to the structural descritptors of the drugs computed by HyperChem software. The proposed models are able to predict the solubility in water-cosolvent mixtures and reduced the mean percentage deviations (MPD) of predicted solubilities from 24%, 48%, and 53% to 16%, 33% and 38%, respectively for water-propylene glycol, water-ethanol and water-polyethylene glycol 400 mixtures, with the overall improvement in prediction capability of the model being approximately 13%.     

Solubility prediction in water-ethanol mixtures based on the excess free energy approach using a minimum number of experimental data

The solubility of nalidixic acid in water-ethanol mixtures has been determined at 25 degrees C. The generated solubility data sets have been used to assess the accuracy of different numerical analyses for the excess free energy model and a new numerical method for solubility prediction in water-ethanol mixtures based on four experimental determinations is proposed. The accuracy of a previously presented numerical method to fit all data points is compared with that of a proposed analysis using average percentage deviation (APD). The APD obtained are 14.6 (+/- 8.0) and 8.4 (+/- 4.1), respectively for previous and proposed methods. A minimum number of three and four data points employed to train the original forms of the excess free energy model and the solubility at other solvent compositions were predicted. The APDs obtained were 61.4 and 23.0%, respectively. The APD produced for the proposed numerical method was 16.1%.     

Correlation of retention factor of analytes in quaternary solvent mobile phases using the Jouyban-Acree model

The Jouyban-Acree model has been used for the mathematical representation of retention factors of phenobarbital, phenytoin and carbamazepine in quaternary aqueous-organic solvent mobile phases. The accuracy of the proposed model is evaluated using average percentage deviation (APD) of experimental and calculated values as an accuracy criterion. The obtained mean and standard deviation of APDs of the model is 4.2 +/- 0.5%. The results showed that the Jouyban-Acree model provided accurate calculations and could be used in practice to speed up the method development process in which quaternary solvent mobile phases are required.     

Mathematical representation of analyte's capacity factor in binary solvent mobile phases using the Jouyban-Acree model

Applicability of a solution model, namely the Jouyban-Acree model, for mathematical representation of capacity factors of phenobarbital, phenytoin and carbamazepine in mobile phases containing water and the organic modifiers: methanol, acetonitrile, acetone and tetrahydrofuran and also a number of data sets collected from the literature has been shown. The accuracy of the proposed model is compared with those of the linear model and the quadratic equation using average percentage deviation (APD) as an accuracy criterion. The obtained mean and standard deviation of APDs of the Jouyban-Acree, linear and quadratic models are 8.1 +/- 8.4, 25.2 +/- 18.0 and 14.5 +/- 16.2%, respectively. The results showed that the Jouyban-Acree model provided more accurate calculations than the previously published models and the mean differences were statistically significant (p < 0.002).     

Migration of ephedrine and salicylic acid from lipid mixtures containing isopropyl myristate

The migration rates of ephedrine and salicylic acid from white soft paraffin-isopropyl myristate mixtures into water have been measured using a previously described procedure. The rates for ephedrine decreased progressively with increasing isopropyl myristate concentration, and this was attributed to the observed accompanying increase in solubility, which decreased the activity of the solute in the solution. Solubility and partition coefficient determinations established that the improved solubility resulted from complexation between ephedrine and isopropyl myristate. In contrast, migration rates of salicylic acid in white soft paraffin-isopropyl myristate mixtures increased with increasing isopropyl myristate concentration up to 50% isopropyl myristate, and then declined. Solubility and partition coefficient determinations indicated that salicylic acid dimerised and also complexed with isopropyl myristate in the lipid mixtures. The diffusion rate profile was attributed to a balance between declining solute-solute and increasing solute-solvent complexation with increasing isopropyl myristate concentration. This mechanism was supported by the behaviour of salicylic acid in Witepsol H15-isopropyl myristate mixtures.     

Solubility behavior of polymorphs I and II of mefenamic acid in solvent mixtures

The dissolution profile and solubility of two polymorphic forms of mefenamic acid were studied in solvent mixtures of ethanol-water and ethyl acetate-ethanol. The solubility parameter (delta) was used to study the effect of polarity on the solubility behavior of the two polymorphs. Differential scanning calorimetry and infrared spectroscopy were performed on the original powders and on the solid phases after contact with the solvent systems for the characterization and identification of the polymorphs. The dissolution rates of both polymorphs is greater in the less polar mixtures (ethyl acetate-ethanol) of lower solubility parameter values. Form II showed larger dissolution rates and saturation concentrations than Form I in all the solvent systems studied. The solid phase of Form II converts totally to Form I after equilibration with the solvents. The rate of conversion was faster in the least polar mixtures. The solubility of both polymorphs reaches a single maximum at 80% ethyl acetate in ethanol, delta = 20.09 MPa1/2. The modified extended Hildebrand method was used to predict the solubility profile of each polymorph. A single equation was obtained for both polymorphs which includes the solubility parameter of the mixtures and the logarithm of the solubility mole fraction of each polymorph in water. The Hildebrand solubility parameter of mefenamic acid is independent of the crystalline form and was determined from two methods giving quite similar values, delta 2 = 20-21 MPa1/2.     

HPLC法测定几种水杨酸类制剂中水杨酸的含量

目的 建立用同一种流动相测定几种水杨酸类制剂水杨酸含量的方法 .方法 采用symmetry C18反相色谱柱,流动相为甲醇-0.02mol·L-1 KH2PO4溶液(60:40,磷酸调pH至3.3);检测波长:297nm.结果 水杨酸在4～80μg.mL-1范围内线性关系良好(r=0.9999),平均回收率为99.42%,日内RSD为0.7%,日间RSD为1.1%.结论 反相高效液相色谱法适用于本类制剂的含量测定,方法简便、灵敏,测定结果 准确.