Nanoparticles and nanocrystals by supercritical CO2-assisted techniques for pharmaceutical applications: A review

Many active ingredients currently prescribed show limited therapeutic efficacy, mainly due to their dissolution rate inadequate to treat the pathology of interest. A large drug particle size creates an additional problem if a specific site of action in the human body has to be reached. For this reason, active ingredient size reduction using micronization/nanonization techniques is a valid approach to improve the efficacy of active compounds. Supercritical carbon-dioxide-assisted technologies enable the production of different morphologies of different sizes, including nanoparticles and nanocrystals, by modulating operating conditions. Supercritical fluid-based processes have numerous advantages over techniques conventionally employed to produce nanosized particles or crystals, such as reduced use of toxic solvents, which are completely removed from the final product, ensuring safety for patients. Active compounds can be processed alone by supercritical techniques, although polymeric carriers are often added as stabilizers, to control the drug release on the basis of the desired therapeutic effect, as well as to improve drug processability with the chosen technology. This updated review on the application of supercritical micronization/nanonization techniques in the pharmaceutical field aims at highlighting the most effective current results, operating conditions, advantages, and limitations, providing future perspectives