Exp. 11 The influence of pH on solubility in water

Exp. 11
The influence of pH on solubility in water
Theory:
Solubilization of poorly soluble drugs is one of the most important physicochemical properties for drug development since more than one-third of drugs are poorly water soluble or water insoluble. In order to prepare a liquid dosage formulation of these drugs, a solubilization technique is usually applied. The most commonly used techniques are pH adjustment, cosolvency, micellization, and complexation.
The solubility of a drug is defined as the maximum quantity of a drug dissolved in a given volume of a solvent at chosen temperature, pressure and pH. For ionizable drugs, the solubility can be affected by the pH of the solution, and the intrinsic solubility (S0) is defined as the concentration of a saturated solution of the neutral form of the drug, in equilibrium with its solid at constant temperature and pressure. Nowadays, drug design approaches based on a combination of chemistry and quantitative structure-activity relationship led to new active substances that are less water soluble and more lipophilic. Not very lipophilic drugs reveal lower solubility in water and have trouble crossing membranes. The acidic group of a drug molecule becomes negatively charged by losing a hydrogen ion at pH < 7. Research in pharmaceutical chemistry has devoted little attention to the physicochemical properties of the chemical leads and has focused mainly on optimization of the in vitro activity. The rate at which a drug goes into the solution when it is dissolved in an acidic or a basic medium is proportional to the solubility of the drug. Many drugs have different solubilities at different pH. These pH-dependent solubility differences lead to pH--dependent dissolution profiles.