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

The equilibrium solution concentration (solubility) is the most important t hermodynamic parameter which defines both extraction and precipitation proc esses. The most demanding applications, for example, those in conjunction w ith the particle formation technology, require reliable and fast determinat ion of solubilities within the low range 10(-9)-10(-4) mole fraction. The p resent 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 (acetaminop hen), ortho, meta, and para isomers of hydroxybenzoic acid and isomers of m ethoxybenzamide. The dynamic on-line method proved to be the most effective , rapid, accurate, and reproducible technique applicable to small amounts o f sample (ca. 25 mg). It has been shown that the solubility measurements ar e a prerequisite in optimization of particle formation technology as well a s in the design of separation and purification processes with supercritical fluids.