Production of drug-releasing biodegradable microporous scaffold impregnated with gemcitabine using a CO2 foaming process

The use of supercritical fluids technology, in particular the use of CO2, is an important advantage over other production techniques of controlled release systems. The impregnation and foaming process can be carried out in a single step. By adjusting the conditions of pressure, temperature, depressurization time or type of polymer used, microcellular scaffolds can be obtained with desired characteristics and adapted to the patient's requirements. Moreover, it has been demonstrated that the use of polymeric solutions allows carrying out impregnation process at mild conditions. In this work, Gemcitabine impregnation in PLGA foams from polymeric solutions of ethyl lactate has been studied. The effect of polymer lactide to glycolide ratio (50:50 or 75:25), pressure (120 or 200 bar) and temperature (25 or 40 degrees C) were studied for three initial drug ratios (175, 105 or 35 mg GEM/g PLGA). Cell size of the foams varied between 35 mu m and 158 mu m, achieving an impregnation efficiency higher than 90 %. Finally, a study of the release profile of Gemcitabine in Phosphate Buffered Saline (PBS) was investigated and a mathematical modelling was carried out. In this model it was considered that the release process was divided into three different steps controlled by the external diffusion in the first place, by the internal transfer of mass in the second and then by the degradation of the polymer.