## 5 Conclusions  
Pharmaceutical nanoparticles and nanocrystals can be successfully processed using scCO\({}_{2}\)-based techniques. The use of one supercritical technique rather than another depends on the processability of the active compounds, which is related to their solubility in scCO\({}_{2}\) or organic solvents, as well as to behavior under certain conditions (e.g., process temperatures). All supercritical processes represent a valid alternative to conventional nanonization methods, generally obtaining smaller particles with narrower PSD and with fewer solvent residues. Techniques based on the use of scCO\({}_{2}\) as a solvent offer some advantages, such as a reduced use of organic solvents; on the other hand, several drawbacks have emerged, such \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Technique** & \
\begin{tabular}{c} **Active** \\ **Compound** \\ \end{tabular} & **Polymer** & **Solvent** &
\begin{tabular}{c} **Operating** \\ **Conditions** \\ \end{tabular} & **Morphology** & **Reference** \\ \hline PGSS & Cyclosporine A & - & - & \(P_{\text{MIXER}}=16\)–\(20\) MPa; & NP & [155] \\ PGSS & Coenzyme Q\({}_{10}\) & PEG & - & \(P_{\text{MIXER}}=20\)–\(25\) MPa; & NP & [37] \\ PGSS & Ibuprofen & PEG & - & \(P_{\text{MIXER}}=75\)–\(80\)\({}^{\circ}\)C & (\(190\) nm) & [31] \\  & Insulin + & & & \(P_{\text{MIXER}}=20\)–\(25\) MPa; & NP & [131] \\ PGSS & human growth & PEG & - & \(P_{\text{MIXER}}=50\)–\(80\)\({}^{\circ}\)C & (\(20\)–\(200\) nm) & [156] \\  & hormone & & & \(P_{\text{MIXER}}=15\) MPa; & NP & [156] \\ PGSS & Riboflavin & FHCO, & \(P_{\text{H}2O}\) & \(P_{\text{MIXER}}=50\)\({}^{\circ}\)C & (\(197\) nm) & [132] \\  & (vitamin B2) & PEG & \(P_{\text{MIXER}}=10\)–\(25\) MPa; & NP & [133] \\ SAA-HCM & Doxorubicin & & acetic acid/ & \(P_{\text{MIXER}}=8\)–\(12\) MPa, & NP & [140] \\  & hydrochloride & Chitosan & \(H_{2}O\) & \(P_{\text{MIXER}}=70\)\({}^{\circ}\)C \(T_{\text{PREC}}\) & (\(120\)–\(250\) nm) & [140] \\  & & & & \(P_{\text{MIXER}}=9\) MPa for & \\  & & & & MeOH and \(9.6\) MPa for & \\  & & & & EtOH & \\ SAA & Erythromicin & - & MeOH, & \(T_{\text{MIXER}}=80\)\({}^{\circ}\)C; \(P_{\text{PREC}}\) & NP & [133] \\  & & & EtOH & \((<500\) nm) & [133] \\  & & & EtOH & & \\ SAA & Lysozyme & - & EtOH/H\({}_{2}\)O & \(P_{\text{MIXER}}=8\) MPa, & \\  & & & & \(T_{\text{MIXER}}=45\)–\(60\)\({}^{\circ}\)C & [157] \\  & & & & \(P_{\text{MIXER}}=8.5\) MPa, & \\ SAA & Rifampicin & PDLLA & AC & \(T_{\text{MIXER}}=80\)\({}^{\circ}\)C; & NP & [36] \\  & & & & \(P_{\text{PREC}}=0.07\) MPa, & (\(123\)–\(148\) nm) & [36] \\  & & & & \(T_{\text{PREC}}=40\)\({}^{\circ}\)C & (\(123\)–\(148\) nm) & [36] \\ SAILA & \(\beta\)-Carotene & - & AC & \(P_{\text{MIXER}}=7\)–\(9\) MPa, & NP & [148] \\  & & & & \(T_{\text{MIXER}}=80\)\({}^{\circ}\)C & (\(37\)–\(90\) nm) & [148] \\ SAILA & \(\alpha\)-Tocopherol & - & AC, EtOH & \(P_{\text{MIXER}}=10\) MPa, & NP & [152] \\  & & & & \(T_{\text{MIXER}}=50\)–\(80\)\({}^{\circ}\)C & (\(220\)–\(240\) nm) & [153] \\ SAILA & Luteolin & Zein & EtOH/H\({}_{2}\)O & \(P_{\text{MIXER}}=9.2\) MPa, & NP & [153] \\  & & & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 3: An overview of nanoparticle production by using CO\({}_{2}\) as a co-solute. NP: nanoparticles; \(P_{\text{MIXER}}\): pressure in the saturator/mixer; \(P_{\text{PREC}}\): pressure; \(T_{\text{MIXER}}\): temperature in the saturator/mixer; \(T_{\text{PREC}}\): precipitator temperature; FHCO: fully hydrogenated canola oil; PDLLA: poly(D,L-)ictide); PEG: polyethylene glycol; AC: acetone; EtOH: ethanol; MeOH: methanol; PGSS: particles from gas-saturated solutions; SAA: supercritical-assisted atomization; HCM: hydrodynamic cavitation mixer; SAILA: supercritical-assisted injection in a liquid antisolvent (SAILA). as the possibility of processing only principles that are soluble in scCO\({}_{2}\), the production of particles with broad PSDs or even agglomerates, and the need for high processing pressures, and sometimes, temperatures.