Modeling of particle size distribution in supercritical antisolvent process

Abstract

In the pharmaceutical industry there are conventional techniques such as milling spray drying liquid antisolvent process to micronize the drug particles in order to enhance the bioavailability by increasing the surface area But the particles produced from these techniques have certain disadvantages such as a broad particle size distribution thermal degradation presence of toxic solvent on drugs etc Therefore there is a need to develop effective particles technologies which could overcome the disadvantages of traditional micronization techniques Supercritical fluid-based micronization techniques are an attractive alternative to the traditional micronization techniques capable of producing pharmaceutical compounds with a narrow particle size distribution and without any thermal and chemical degradation as well as no residual solvent content A fluid is described as a supercritical fluid when its temperature and pressure is above its critical temperature and pressure Carbon dioxide CO2 is the most widely used fluid in supercritical fluidbased micronization techniques as its critical temperature and pressure are mild In this work a supercritical antisolvent process in which carbon dioxide is acting as an antisolvent has been modeled The drug molecule considered in this work is rifampicin This drug is first dissolved in dimethyl sulfoxide and this solution is then atomized into droplets through a nozzle into a vessel which is filled with supercritical CO2 These droplets which are a binary mixture of drug molecules and solvent become a ternary mixture in the vessel as supercritical CO2 diffuses into the droplet Rifampicin is insoluble in supercritical CO2 and there is a high miscibility between supercritical CO2 and the solvent which leads to a high and fast diffusion of supercritical CO2 into the droplet Due to this antisolvent effect of supercritical CO2 the solubility of rifampicin in the ternary mixture decreases sharply leading to the start of nucleation and growth In the mathematical model presented in this work