Solubility determination of compounds of pharmaceutical interest

Abstract

Solubility determination is one of the most important parameters to study when developing a new drug. Solubility gives information about the tendency of the compound to be dissolved when having a particular liquid media surrounding it. Ensuring the drug solubility in body fluids enhances bioavailability which is completely necessary to have the desired effect on cells. A significant factor that must be taken into consideration while determining solubilities is the possibility of most compounds of pharmaceutical interest to have ionisable groups. The presence of acid and/or basic groups in the molecule would imply a variation of the solubility with the pH. Therefore, depending of the pH of the media and the pKa of the molecule, it will be ionised or in its neutral form and as a consequence, its solubility will vary. In this work, two ionisable drugs relatively insoluble have been studied: pioglitazone which is an amphoteric substance and glimepiride which is an acidic compound. In order to determine solubility, shake-flask method has been used. Although there are other recognized procedures, shake-flask is the reference method to carry out solubility determinations. It consists of reaching the thermodynamic equilibrium between a saturated solution and the precipitated solid at different pH. Then, the supernatant is analysed through HPLC to determine solubility and, as the solubility is measured for the solid in equilibrium with the saturated solution, the solid is analysed by X-Ray diffraction to know which compound and in which polymorphic form is being studied. As a result, the solubility-pH profile of the compound is obtained