Determination of the solubility and thermodynamic properties of codeine phosphate in the binary mixtures of polyethylene glycol 400 and ethanol at different temperatures

Abstract

Due to the low water solubility of most drugs, improving this feature is one of the important steps in drug research and development. One of the simplest and oldest ways to solubility increase is the use of cosolvent. In addition, to understand the effect of construction parameters in the solubility increasing of drugs and also to predict their solubility in different solvent systems to save time and money, modeling can be used with the various mathematical models. Aim:In the present study, the solubility and density of codeine phosphate in mixtures of polyethelene glycol 400 + ethanol at temperature range of 293.2 to 313.2 K were investigated. The correlations between the obtained data and different models of solubility have also been investigated.Method:The shake-flask method is used for determination of the solubility. After preparing and saturating the selected solvent mixtures with the studied drug, it is placed on the shaker for a certain time inside the incubator at a certain temperature until the solution is saturated and reaches equilibrium. Then the solution is centrifuged and after proper dilution, its absorption is recorded at the maximum wavelength for the drug and the concentration of saturated solutions is obtained using the drawn calibration curve. Finally, the correlation of experimental data with computational models is examined.Results:The solubility of codeine phosphate is directly related to the increase of temperature, and polyethylene glycol 400 in the solvent mixtures. Also, by increasing the mass fraction of polyethylene glycol 400 solvent in polyethylene glycol 400 + ethanol system, codeine phosphate solubility increases exponentially.Conclusion :The obtained data show that the highest solubility of codeine phophate with increasing temperature and cosolvent. The obtained data analyzed with different models and the constants of each model were calculated.