Study of the maturation of a ketaprofen B-cyclodextrin mixture assisted by supercritical fluid
Résumé
Supercritical fluids have found many applications due to their versatile physicochemical properties. They can be used as media for the formation of inclusion complexes, for helping encapsulation of an active substance into cyclodextrin (CDs) cavities. In addition, several active pharmaceutical substances such as ketoprofen, are not very polar, thus not very water-soluble, and in order to increase their rate of dissolution, such drugs can be included in a molecular cage, such as CD with the aid of supercriticalfluid processing. Several inclusion processes in supercritical media have been developed and the maturation process, in which supercritical carbon dioxide (SC-CO 2) is generally used, is among the most recent. It consists of using supercritical CO 2 to bring the active substance, the cyclodextrin and a quantity of water in contact one with another over certain duration, in order to obtain an inclusion complex. We have also studied the influence of several operating parameters on the inclusion rate e.g pressure, temperature, duration of maturation, density of the SC-CO 2 , agitation and factors related to the physical mixture, the amount of water, the molar ratio-cyclodextrin/ketoprofen and the mass ratio SC-CO 2 /mixture, as well as the effect of the method of preparation of the physical mixture on inclusion. We found that pressure, temperature, duration of maturation, agitation and density of SC-CO 2 all had a positive effect on inclusion of ketoprofen (KP) in-cyclodextrin (-CD). The stoichiometry of inclusion of KP in-CD is 1:2. The method of preparation of the powder mixture and mass ratio SC-CO 2 /mixture has an effect on inclusion.
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