Physicochemical characterization of drug-cyclodextrin complexes prepared by supercritical carbon dioxide and by conventional techniques

摘要

The objective of this study was to investigate the effectiveness of supercritical carbon dioxide (SC CO2) technique for preparing solid complexes between β-cyclodextrin and three local anesthetic agents (benzocaine, bupivacaine, and mepivacaine) by comparing it to more traditional methods such as kneading, co-evaporation, co-grinding, and sealed-heating. Effects of variation of experimental conditions, i.e. temperature, pressure and exposure time, on the products prepared by SC CO2 method were also examined. The products obtained were characterized by powder X-ray diffractometry and Fourier transform infrared spectroscopy, and tested for dissolution properties. Results suggested the possibility of complex formation between β-cyclodextrin and the three anesthetic agents, and indicated that it was influenced by the preparation technique. The co-grinding method was the only one resulting in completely amorphous products for all three drugs. Almost amorphous products, with only limited residual crystallinity, were obtained by co-evaporation and kneading techniques, while SC CO2 and sealed-heating methods gave rise to more crystalline systems. As for the SC CO2 method, temperature (for benzocaine and bupivacaine) or exposure time (for mepivacaine) had significant effects on the solid-state properties of the final products. Dissolution studies indicated that all the examined methods were more effective than the simple physical mixing in improving drug dissolution properties, but the different rank orders observed for the different drugs suggested that there is no general rule for the selection of the most effective preparation method, which depends on the type of drug-Cyd system considered. Nevertheless, in all cases, products obtained by the SC CO2 method showed satisfactory dissolution properties.