Solubility Parameter Estimation of Celecoxib by Current Methods

Models for predicting solubility of drugs in solvent mixtures have an important practical application in drug formulation. Solvent mixtures are widely used in pharmacy, and theoretical and semiempirical approaches save experiments that are often expensive and time-consuming. The study of solubility behaviour of celecoxib in solvent blends and individual solvents ranging from non-polar to highly polar is essential. The total solubility parameter and partial solubility parameters explain the interactions of the drug. The solutions containing excess drug were shaken in a water bath for 72 h at 25°C. The solutions attained equilibrium were then filtered and analysed for drug content. The extended Hildebrand solubility approach was used to process the solubility data of celecoxib. For understanding the solute-solvent interactions, partial solubility parameters concept was utilized. A multiple regression method using the extended Hansen’s partial solubility parameters was applied to verify the solubilities of celecoxib in pure polar and nonpolar solvents and to predict its solubility in untested solvents. Group contribution methods were used to calculate the solubility parameter of celecoxib and to support the results obtained from various theories. The three parameter approach and the Flory-Huggins size correction term ‘B’ give the prediction of solubility with correlations up to 92%. The four-parameter approach involving protondonor and proton-acceptor parameters is also used in fitting the solubility data. The correlations are appreciable (96%). There is a considerable evidence to suggest that celecoxib is soluble in solvents, through acid - base parts of molecule. A criterion of the ideal mole fraction solubility intersecting the mole fraction solubility curve is proved to be successful in deciding the solubility parameter of celecoxib. The celecoxib solutions behave as irregular solutions. The total solubility parameter of celecoxib determined from the different methods of data analysis is finally assigned at 11 H. The partial solubility parameters obtained from four-parameter approach are δ_2d = 7.88, δ_2p = 2.49, δ_2a = 2.12, and δ_2b = 3.54, which give insights into the interaction capability of celecoxib and are consistent with its chemical structure.

Models for predicting solubility of drugs in solvent mixtures have an important application in drug formulation. The study of solubility behaviour of celecoxib in solvent blends and individual solvents ranging from non-polar to highly polar is essential. The total solubility parameter and partial solubility parameters explain the interactions of the drug. The solutions containing excess drug were shaken in a water bath for 72 h at 25°C. The solutions attained equilibrium were then filtered and analysed. The extended Hildebrand solubility approach was used to process the solubility data of celecoxib. For understanding the solute-solvent interactions, partial solubility parameters concept was utilized. A multiple regression method using the extended Hansen’s partial solubility parameters was applied to verify the solubilities of celecoxib in polar and nonpolar solvents and to predict its solubility in untested solvents. The three parameter approach and the Flory-Huggins size correction term ‘B’ give the prediction of solubility with correlations up to 92%. The four-parameter approach give appreciable correlations (96%). There is a considerable evidence to suggest that celecoxib is soluble in solvents, through acid - base parts of molecule. A criterion of the ideal mole fraction solubility intersecting the mole fraction solubility curve is proved to be successful in deciding the solubility parameter of celecoxib. The total solubility parameter of celecoxib determined from the different methods of data analysis is finally assigned at 11 H. The partial solubility parameters obtained from four-parameter approach give insights into the interaction capability of celecoxib and are consistent with its chemical structure.