Nanoparticles and Nanocrystals by Supercritical CO2-Assisted Techniques for Pharmaceutical Applications: A Review

Abstract

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.

Supercritical Carbon Dioxide as a Green Alternative to Achieve Drug Complexation with Cyclodextrins

“…The supercritical fluid technology can be used to achieve particle formation and many examples of novel pharmaceutical manufacturing processes can be found in the literature [8]. The processes can be categorized based on the different role of scCO 2 , which can act as a solvent, an antisolvent or a co-solute [8,105]. Even though many scCO 2 soluble cyclodextrins are reported in the literature, until now examples of particleformation techniques where scCO 2 acts as a solvent have not been employed to achieve drug/cyclodextrin complexation.…”

“…ASES, which is also known as the precipitation with compressed antisolvent (PCA) method, is a semicontinuous process (Figure 4a). This process generally leads to precipitated particles with smaller size and stricter particle size distribution with respect to GAS [105]. ScCO 2 is continuously introduced at a fixed flowrate into the precipitation vessel, which is maintained at constant temperature and pressure.…”

“…The main difference lies in the atomization device, which consists in a coaxial nozzle that provides the simultaneous introduction of the solution and the supercritical solvent [6]. This involves a tangential impact between the two fluids, which promotes better mixing so leading to the production of finer powders and preventing particle aggregation [6,105].…”

“…[6]. In particular, the higher the pressure in the precipitation chamber the smaller is the particle size, which may range from the micro-to the nanoscale [105]. Reverchon and coworkers [106] have recently reported a comprehensive discussion of the coprecipitation mechanism in SAS processes and the role of the working conditions on particle size and morphology, which can be applied also to drug/cyclodextrin formulations [48,51].…”

Preparation and Characterization of Fenofibrate Microparticles with Surface-Active Additives: Application of a Supercritical Fluid-Assisted Spray-Drying Process

“…In the SA-SD process, SC-CO 2 acts both as a co-solvent that is miscible with the drug solution to be treated and as an atomizing agent that can atomize the drug solution in a fine droplet. Moreover, organic and inorganic solvents can be used for fine particle formation of both hydrophilic and hydrophobic drugs [49,[51][52][53][54][55][56][57].…”