Progesterone (PRG) and testosterone (TST) were impregnated on mesoporous silica (ExP) particles via supercritical carbon dioxide (scCO2) processing at various pressures (10–18 MPa), temperatures (308.2–328.2 K), and time (30–360 min). The impact of a co-solvent on the impregnation was also studied at the best determined pressure and temperature. The properties of the drug embedded in silica particles were analysed via gas chromatography (GC), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and nitrogen adsorption. An impregnation of 1 to 82 mg/g for PRG and 0.1 to 16 mg/g for TST was obtained depending on the processing parameters. There was a significant effect of pressure, time, and co-solvent on the impregnation efficiency. Generally, an increase in time and pressure plus the use of co-solvent led to an improvement in drug adsorption. Conversely, a rise in temperature resulted in lower impregnation of both TST and PRG on ExP. There was a substantial increase in the dissolution rate (> 90% drug release within the first 2 min) of both TST and PRG impregnated in silica particles when compared to the unprocessed drugs. This dissolution enhancement was attributed to the amorphisation of both drugs due to their adsorption on mesoporous silica. Graphical Abstract