Effect of process variables on imiquimod micronization using a supercritical antisolvent (SAS) precipitation technique

Abstract

This study aimed to promote the micronization of imiquimod, a poorly water-soluble immunostimulant drug, using the supercritical antisolvent (SAS) process. The effect of temperature, pressure and drug concentration on drug particle formation, size and yield was evaluated. Increasing pressure tends to increase size and decrease yield. Increasing concentration results in raises in size and yield. Increasing temperature leads to size reduction and increase in yield. The combination of process variables shows that increase in pressure and concentration leads to an increase in size and a reduction in yield, and that pressure and temperature combined, as well as the combination of temperature and concentration, leads to reduction in size and yield. The micronization process was not capable of promoting improvement in drug dissolution rate or limit. However, a significant gain was observed in data reproducibility, which can contribute considerably to the quality control of formulations containing imiquimod.