Solubility and thermodynamic parameters of a novel anti-cancer drug (DHP-5) in polyethylene glycol 400 + water mixtures (original) (raw)
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A trained version of Jouyban-Acree model is proposed employing 32 solubility data sets of 5 drugs in ethanol + propylene glycol mixtures at various temperatures. Using this model, the solubilities of a drug in the mono-solvents and the Abraham solvation parameters are required to predict the solubility in the binary solvent mixtures. The overall mean percentage deviation for the correlated data was 11.0 %, and that of a predicted data set was 11.2 %.
Journal of Pharmaceutical Sciences, 2012
A method is presented for determining the equilibrium solubility of a drug in a solid polymer at or near room temperature, which represents a typical storage temperature. The method is based on a thermodynamic model to calculate the Gibbs energy change G SS associated with forming a binary drug-polymer solid solution from the unmixed polymer and solid drug. The model includes contributions from heat capacity differences between the solid solution and the corresponding unmixed components, breaking up of the solid drug structure, and drug-polymer mixing. Calculation of G SS from thermal analysis data is demonstrated, and it is shown that minima of plots of G SS versus the dissolved drug concentration represent the equilibrium drug solubility in the polymer. Solid solutions were produced for drug-polymer systems (griseofulvin, indomethacin, itraconazole; PVP K30, Eudragit L100, Eudragit E100) in drug weight fractions up to ∼25%. At 25 • C, it was seen that heat capacity effects were important in determining the drug solubility. It was concluded that drug solubilities in solid polymers can be determined using thermal analysis, and must include heat capacity effects when evaluated near room temperature.
The E and C model for predicting the solubility of drugs in pure solvents
International Journal of Pharmaceutics, 1996
The E and C model for hydrogen bonding is used together with nonspecific solubility parameters to predict the solubility of a Lewis base solute in a series of solvents of several chemical classes. A linear relationship between enthalpies of hydrogen bonding calculated from the Drago model and entropies obtained from a few experimental solubilities allows the prediction of the entropy contribution for the other solvents. Correct orders of magnitude are predicted in solvents of all polarities (from benzene to glycerin) which were not used to obtain the empirical relationships. The results suggest that the E and C model may be useful to reduce the experimental work usually needed for predicting solubility of drugs in pure solvents of different acid-base characteristics.
European Journal of Pharmaceutical Sciences, 2020
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Solubility Prediction of Drugs in Mixed Solvents Using Partial Solubility Parameters
Journal of Pharmaceutical Sciences, 2011
Solubility of drugs in binary and ternary solvent mixtures composed of water and pharmaceutical cosolvents at different temperatures were predicted using the Jouyban-Acree model and a combination of partial solubility parameters as interaction descriptors in the solution. The generally trained version of the model produced the overall mean percentage deviation values for the back-calculated solubility of drugs in binary solvents of 34.3% and the predicted solubilities in ternary solvent mixtures of 38.0%. In addition, the applicability of the trained model for predicting the solvent composition providing the maximum solubility of a drug was investigated. The results of collected solubility data of drugs in various mixed solvents and the newly measured solubility data of five drugs in ethanol + propylene glycol + water mixtures at 25 • C showed that the model provided acceptable predictions and could be used in the pharmaceutical industry.
Recent Advances in Thermo and Fluid Dynamics, 2015
In this chapter, the applicability of two predictive activity coefficient-based models will be examined. The experimental data from five different types of VLE (vaporliquid equilibrium) and VLLE (vapor-liquid-liquid equilibrium) systems that are common in industry are used for the evaluation. The nonrandom two-liquid segment activity coefficient (NRTL-SAC) and universal functional activity coefficient (UNI-FAC) were selected to model the systems. The various thermodynamic relations existing in the open literature will be discussed and used to predict the solubility of active pharmaceutical ingredients and other small organic molecules in a single or a mixture of solvents. Equations of states, the activity coefficient, and predictive models will be discussed and used for this purpose. We shall also present some of our results on solvent screening using a single and a mixture of solvents.
Journal of Chemical & Engineering Data, 2010
Experimental solubilities of 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine-4-oxide (chlordiazepoxide), 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one (diazepam), and 7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one (lorazepam) in (propane-1,2-diol + water) at T ) 303.2 K were reported. The solubility of drugs increased with the addition of propane-1,2-diol and reached the maximum values in pure propane-1,2-diol. The Jouyban-Acree model was used to fit the experimental data, and the solubilities were reproduced using a previously trained version of the Jouyban-Acree model and the solubility data in monosolvents in which the overall mean relative deviations (OMRDs) of the back-calculated and predicted values with the corresponding experimental data were 4.2 % and 10.7 %. The solubilities of the three drugs were also predicted using a trained version of the log-linear model of Yalkowsky, and the OMRD was 21.1 %.
Journal of Pharmaceutical Sciences, 1993
A modification of the extended Hansen method is used for estimating the solubility of sulfadiazine and other organic drug molecules in a number of individual solvents ranging from nonpolar to highly polar. The equations obtained for each drug involve the partial solubility parameters of the solvents and allow the prediction of solubility of these drugs in a new solvent. Furthermore, a number of drugs (e.g., sulfadiazine, sulfamethoxypyridazine, naphthalene, and some benzoic acid derivatives) are combined in a single expression including the ideal solubility of the drugs and the partial solubility parameters of the solvents. The equation fits the solubilities of these drugs in a wide variety of solvents and may be used to predict the solubility of other sulfonamides and benzoic acid derivatives in semipolar and highly polar solvents. The solvatochromic parameter approach is also used in models for predicting the solubility of single drugs in individual solvents. It was tested with multiple solutes as was the partial solubility parameter approach. However, the latter approach is superior; the parameters of the solubility parameter method are all statistically significant for drugs tested individually or together in a single equation, a condition that is not obtained with the solvatochromic model.
Chemical & Pharmaceutical Bulletin, 2002
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°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°C showing reasonably accurate predictions. This is important in pharmaceutics because it save experiments that are often expensive and time consuming.