Carrier-dependent pressure of maximum loading in supercritical CO₂ drug impregnation: Ibuprofen and ketoprofen in MCM-48 with a three-dimensional pore network

Mesoporous silica is an attractive carrier for poorly water-soluble drugs, and supercritical fluid deposition (SCFD) with CO₂ loads them without organic solvents. The loading passes through a maximum with impregnation pressure, commonly attributed to the opposing effects of CO₂ density on drug solubility and competitive CO₂ adsorption. Because solubility is a property of the drug–CO₂ pair alone, the pressure of the maximum might be assumed transferable between carriers, but pressure-resolved data for ordered mesoporous silicas exist only for one-dimensional channels. Ibuprofen and ketoprofen were impregnated into MCM-48, with a three-dimensional bicontinuous pore network, at 333 K and 8–21 MPa; loadings were measured by thermogravimetry and pore structures by nitrogen adsorption. Among the pressures examined, the loading of both drugs was highest at 18 MPa, versus 15 MPa in published SBA-15 data. The ketoprofen data support the shift: loading fell by 33% from 15 to 17 MPa on SBA-15 but rose by 20% from 15 to 18 MPa on MCM-48; for ibuprofen, the differences near the maximum are within the reproducibility. As the silicas also differ in surface area and pore size, its cause was not isolated. The occupied-volume ratio R , the pore volume made inaccessible to nitrogen per volume of drug loaded, was 0.8–1.1 for ibuprofen up to 18 MPa and 2.2–3.2 for ketoprofen, which we interpret as nearly volumetric filling by ibuprofen and obstruction of pore entrances by ketoprofen. The pressure of maximum loading thus depends on the carrier and should be verified for each drug–carrier system.