Determine Drug Solubility in Supercritical Carbon Dioxide from First-Principles Calculations and Experiments and Its Application

Supercritical carbon dioxide (SCCO2), due to its specific properties, is widely used in industries, such as extraction of natural flavors, decaffeination of coffee beans, reaction media of polymer synthesis, purification and recrystallization of drugs, and nanomedicine applications. The solubility of drug compounds in ScCO2 is crucial information for the design and optimization of purification, recrystallization, and micronization using ScCO2 with/without organic solvents. If an organic solvent is involved in the process, it is more complicated to describe the phase behavior of the system. This proposal is aimed at developing a general approach for studying the complicated phase behavior of system composed of drug compounds and ScC〇2. The proposed work focuses on two major topics:1.Experimental measurements: set up an apparatus to measure drug solubility in ScCO2 and use our apparatus to investigate high pressure VLE for binary mixtures of CO2 + low molar mass organic solvents.2.Theoretical computations: systematically understand the applicability of the first-principles based thermodynamic model in describing solid-liquid-gas phase equilibrium for binary mixtures of drug + ScCO2.Based on PI5s previous experiences on both theoretical computation and experimental measurement in the field of chemical engineering thermodynamics, PI will effectively combine all research resources from MOST, NCU, and NCHC to lead the research group to focus on both experimental measurement and theoretical computation in next three years. Through this three-year proposal, it is expected to produce high-impact works published in international journals and to provide consultation to industrial companies in Taiwan.