Micro and nanosizing of amiodarone hydrochloride drug via subcritical water anti-solvent technology

As a green and bio-friendly technology, subcritical water (SW) processes have attracted considerable attention for micro and nanoparticle production in pharmaceutical applications. In this study, the solvent-antisolvent precipitation method was utilized for the first time to fabricate nanoparticles of amiodarone hydrochloride (AMD), an antiarrhythmic drug. The Design of Experiments (DOE) was applied to evaluate the simultaneous effects of three different variables, including SW temperature 373.15 K to 393.15 K, polyethylene glycol concentration 0.01 wt% to 0.03 wt%, and antisolvent temperature 273.15 K to 293.15 K, to discover the desirable conditions for achieving the smallest particle size. The desirable procedure conditions were determined as follows: SW temperature (393.15 K), polyethylene glycol concentration (0.03 wt%), and antisolvent temperature (283.15 K). Results indicated that under these conditions, the particle size was significantly reduced (average size of 28 nm) using green technology without requiring organic solvents or corresponding post-processing purification stages.