Prediction of drug solubility in lipidic surfactant and cosolvent mixtures: Investigation of the modeling approach and thermodynamic analysis of solubility

The knowledge of the solubility of pharmaceuticals in pure solvents and solvent mixtures is crucial for designing the S(M)EDDS of poorly soluble drug substances. The first step in finding optimal crystallization conditions is usually a solvent screening process. Since, experiments are very time consuming, a model, which allows for solubility predictions in pure solvents and solvent mixtures based only on a small amount of experimental data is required. In this work, we investigated the predictability of mathematical models for a solute in binary and ternary solvent system. Additionally, with the help of van't Hoff analysis the thermodynamic behavior of solutions were carried. Clotrimazole and Fluconazole were used whose solubility was measured in single solvent as a function of temperature and the data obtained was applied in the mathematical models which can predict solubility in multi component system. The experimental data were .then correlated with the estimated values obtained from exponential model and log-linear model of Yalkowsky.;Few literatures surveys has revealed that predicting the solubility in lipid microemulsions may be quite complicated due to the interfacial nature of these systems and distribution of the drug in continuous/dispersed phase and sometimes preferred locations at the surfactant interface. The efficiency of the design of lipid formulations could be improved if the solubility of a drug in a lipid mixture could be estimated which could be helpful in early stage of drug development where a decision needs to be made as to whether a particular drug is potentially developable. In addition to solubility estimation, a systematic study of solubility behavior was also covered in this work. The factors governing the lipid solubility can be better understood by conceptualizing the thermodynamic components involved in solubilization such as Gibb's free energy of mixing, enthalpy, entropy of solution and activity coefficient. These factors were calculated with the help of Van't Hoff solubility equation and ideal solubility theory.;Further, all the models were treated with linear, log linear and power mixing rules in order to analyze how the model dependent parameters are related.