Evaluation of supercritical fluid technology as preparative technique of benzocaine?cyclodextrin complexes?Comparison with conventional methods

Evaluation of supercritical fluid technology as preparative technique of benzocaine?cyclodextrin complexes?Comparison with conventional methods
Received 4 June 2006; accepted 26 August 2006. Available online 28 September 2006.
Ali H. Al-Marzouqia, , , Baboucarr Jobea, Ali Dowaidara, Francesca Maestrellib and Paola Murab
Journal of Pharmaceutical and Biomedical Analysis
Volume 43, Issue 2 , 17 January 2007
ScienceDirect
Copyright ? 2006 Elsevier B.V. All rights reserved.
aDepartment of Chemical & Petroleum Engineering, UAE University, Al-Ain, P.O. Box 17555, UAE
bDepartment of Pharmaceutical Sciences, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Firenze, Italy
Abstract
The objective of this study was to investigate the effect of the preparation method on the physico-chemical properties of complexes prepared between ?-cyclodextrin (?-Cyd) and benzocaine (BZC). In particular, the effectiveness of a new technique based on supercritical carbon dioxide (SC CO2) 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 CO2 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 CO2 method revealed to be an effective technique for preparing solid systems between ?-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 CO2 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 CO2 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.
Keywords: Supercritical fluid carbon dioxide; Benzocaine; ?-Cyclodextrin; Characterization; Dissolution

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