Selection of Solvent in Supercritical Antisolvent Process

Abstract

Supercritical antisolvent process (SAS) is widely being used to micronize the pharmaceutical compounds. The advantage of SAS process is that thermal degradation does not occur in the pharmaceutical compounds as the operating temperature is near to room temperature. This process starts with the atomization of a solution, a mixture of pharmaceutical compound and solvent, in the supercritical carbon dioxide environment. The transfer of carbon dioxide (antisolvent) to the droplet decreases the solubility of solute in the solution causing precipitation of solute in micro to nano-particle size range. In this work, four solvents: dimethyl sulfoxide, ethanol, acetone and dichloromethane have been considered to study the effect of solvent on droplet diameter, solvent mass transfer rate into supercritical carbon dioxide environment and velocity profile. The atomized droplet moves downward and mass transfer takes place. Two film theory of mass transfer has been used to calculate the molar flow rate of solvent into supercritical environment and carbon dioxide into droplet. Due to this two way mass transfer, composition of the droplet and thus size is changing continuously. The size of the droplet is calculated assuming that the droplet remains spherical during its downward movement. The size depends on the total number of moles in the droplet and molar density. Peng-Robinson equation of state has been used to calculate the molar density. The velocity profile of droplet is calculated using force balance equation on a moving body in a medium. Result shows that dichloromethane is the best solvent as it has small initial droplet diameter and less residence time compare to other solvents.