In situ investigation of supercritical CO2 assisted impregnation of drugs into a polymer by high pressure FTIR micro-spectroscopy

An original experimental set-up combining a FTIR micro-spectrometer with a high pressure cell has been built in order to analyze in situ the impregnation of a solute into microscopic polymer samples, such as fibers or films, subjected to supercritical CO2. Thanks to this experimental set-up, key factors governing the impregnation process can be simultaneously followed such as the swelling of the polymeric matrix, the CO2 sorption, the kinetics of impregnation and the drug loading into the matrix. Moreover, the solute/polymer interactions and the speciation of the solute can be analyzed. We have monitored in situ the impregnation of aspirin and ketoprofen into PEO (Polyethylene Oxide) platelets at T = 40 °C and P = 5; 10 and 15 MPa. The kinetics of impregnation of aspirin was quicker than the one of ketoprofen and the final drug loading was also higher in the case of aspirin. Whereas the CO2 sorption and the PEO swelling remain constant when PEO is just subjected to CO2 under isobaric conditions, we noticed that both parameters can increase while the drug impregnates PEO. Coupling these results with DSC measurements, we underlined the plasticizing effect of the drug that also leads to a decrease in the crystallinity of PEO in situ thus favoring the sorption of CO2 molecules into the matrix and the swelling of the matrix. The plasticizing effect increases with the drug loading. Finally, the speciation of drugs was investigated considering the shift of the carboxyl bands of the drugs. Both drugs were found to be mainly homogeneously dispersed into PEO.