Evaluation of supercritical fluid technology as preparative technique of benzocaine-cyclodextrin complexes--comparison with conventional methods.

The objective of this study was to investigate the effect of the preparation method on the physico-chemical properties of complexes prepared between beta-cyclodextrin (beta-Cyd) and benzocaine (BZC). In particular, the effectiveness of a new technique based on supercritical carbon dioxide (SC CO(2)) for preparing solid drug-cyclodextrin complexes was investigated and compared to other more conventional methods such as kneading (KN), co-evaporation (COE), co-grinding (GR) and sealed-heating (S.H.). Effects of temperature, pressure and exposure time on the properties of complexes prepared by SC CO(2) technology were also studied. The different systems were characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometry (PXRD) and dissolution test according to the dispersed amount method. The co-grinding (GR) method resulted in amorphous products while other methods led to crystalline or partially amorphous products depending on both the method and its experimental conditions. SC CO(2) method revealed to be an effective technique for preparing solid systems between beta-cyclodextrin and benzocaine, avoiding the use of organic solvents (and problems of their complete removal) and allowing an easy scale-up of the process. As for the influence of the experimental conditions in promoting the solid-state drug-carrier interaction when using the SC CO(2) method, temperature seemed to play the major role, whereas pressure and exposure times had more limited effects. Dissolution tests confirmed a limited but favourable effect in increasing the exposure time, while indicated a possible interaction effect between temperature and pressure in influencing the dissolution performance of the final product. The best product obtained by the SC CO(2) method showed dissolution properties similar to those of the co-ground product and only slightly lower than the system obtained by sealed-heating, which was the most effective technique.