PL1 UNDERSTANDING SOLUBILITY OF THE MOLECULE
Dionigio Franchi, Robert W. O’Connor · 2008
A good understanding of a baseline solubility characterization is fundamental in order to guide the selection of formulation approaches and accurate predicts improvements of API solubility and/or dissolution by both chemical (salts and prodrugs) and formulation (i.e. particle size reduction, lipid formulation and cyclodextrine complexation) approach. Solubility of Active Pharmaceutical Ingredient (API) has always been a concern for formulators, since inadequate aqueous solubility may limit bioavailability of oral products. In recent years, number of low solubility compounds has increased within the pharmaceutical industry pipeline. This challenge has been faced by the pharmaceutical industry by improving knowledge of important physico-chemical characteristic such as solubility, ionization constant and partition coefficient. Solubility of drugs is influenced by many variables (pH, solid state, presence of counter-ions, temperature, etc…). Even though a single point determination has some value, profiling the solubility of a compound as a function of one more of these variables often yields a wealth of information. A data fitting approach for determination of pH solubility profile will be presented. Characterization of the solid in equilibrium with different solution media will be discussed. Biorelevant solubilities will be also taken in consideration through the use of simulated gastro-intestinal fluids. Building on the equilibrium solubility knowledge, these data will be used in order to speculate on a theoretical in-vivo profile to be correlated with drug product performance.