Development of a novel continuous dense gas process for the production of residual solvent-free self-assembled nano-carriers

Abstract

A continuous dense gas process has been developed based on the principles of process intensification. The continuous process is designed for the production of self-assembled nano-carriers for pharmaceutical applications such as liposomes, polymersomes, and micelles. Carbon dioxide (CO2) is being used during the dense gas process. The dense gas CO2 process is regarded as a green technology since the process does not generate CO2 as a product, but uses the existing CO2 from the environment for the process. Removal of residual solvent is a key aspect of pharmaceutical formulation and an effective single-step process to achieve that endpoint has been demonstrated. Ethanol and dichloromethane were investigated as residual organic solvents to be removed by CO2. Dichloromethane was eliminated to a level undetectable by gas chromatography, while ethanol content was reduced down to 1.70 wt % with an extraction efficiency of 95.7%. The average hydrodynamic diameter of polymersomes produced by the continuous process was 300 ± 10 nm. The present study provides a basic platform for up-scaling the production of self-assembled nano-carriers.