Solubility analysis of drug compounds in supercritical carbon dioxide using static and dynamic extraction systems

The equilibrium solution concentration (solubility) is the most important thermodynamic parameter which defines both extraction and precipitation processes. The most demanding applications, for example, those in conjunction with the particle formation technology, require reliable and fast determination of solubilities within the low range 10(-9)-10(-4) mole fraction. The present work aimed to develop and evaluate two experimental systems based on static recirculation and dynamic through-flow extraction methods combined with high-performance liquid chromatographic off-line and spectroscopic on-line analytical modes. The model compounds included paracetamol (acetaminophen), ortho, meta, and para isomers of hydroxybenzoic acid and isomers of methoxybenzamide. The dynamic on-line method proved to be the most effective, rapid, accurate, and reproducible technique applicable to small amounts of sample (ca. 25 mg). It has been shown that the solubility measurements are a prerequisite in optimization of particle formation technology as well as in the design of separation and purification processes with supercritical fluids.