A green organic-solvent-free route to prepare nanostructured zinc oxide carriers of clotrimazole for pharmaceutical applications

Abstract In the context of proposing cleaner production strategies for the pharmaceutical industry, an organic-solvent-free route to prepare nanostructured zinc oxide (NsZnO) reservoirs of clotrimazole (CTZ) was studied. Two different NsZnO materials were synthesized, selecting wet chemical approaches without any organic solvents: chemical bath deposition and a soft-template sol-gel method. Both materials showed a pure crystalline wurzite structure with two different morphologies: aggregates of nanosheets or interconnected nanoparticles. For the former material the specific surface area and the pore volume reached the values of 66 m 2 /g and 0,230 cm 3 /g, respectively, which were higher than those of the latter (19 m 2 /g and 0,050 cm 3 /g). For the first time, the loading of CTZ in a ZnO carrier was performed using supercritical CO 2 as a solvent. The NsZnO materials were characterized, before and after the drug loading, by FESEM, EDS, XRD, nitrogen adsorption isotherms, TGA, DSC. CTZ was dispersed in the NsZnO carrier in amorphous form, with a maximum loading of 17% w/w. The decrease of specific surface area and pore volume upon drug loading for both samples is ascribed to the adsorption of CTZ molecules on the surface of the NsZnO materials. This confirms the feasibility of using the NsZnO as a CTZ carrier. In vitro drug-release was investigated and revealed that the NsZnO carrier can deliver CTZ with a faster release of a larger drug amount when compared to the solid crystalline drug. The novel clean preparation route of a ZnO carrier for CTZ delivery herein presented is easily adabtable to batch small-scale pharmaceutical industrial process.