Preparation of amphiphilic cyclodextrin nanospheres using the emulsification solvent evaporation method.: Influence of the surfactant on preparation and hydrophobic drug loading

In this study we verified the feasibility of preparing nanospheres from an amphiphilic 2,3-di-O-hexanoyl-gamma-cyclodextrin (gamma CDC6) using the emulsification solvent evaporation method. This preparation method consists in emulsifying an organic phase containing the cyclodextrin in an aqueous phase containing Pluronic F68 as surfactant. The influence of the process parameters, i.e. surfactant concentration and initial gamma CDC6 content, on the characteristics of nanosphere preparation, as well as on the nanosphere loading of a hydrophobic drug, progesterone, was evaluated. Cyclodextrin nanospheres presenting a mean diameter varying from 50 to 200 nm were obtained, even in the presence of low surfactant concentration. The formation of colloidal particles in these conditions was associated with the amphiphilic properties of the cyclodextrin derivative. However the partitioning of the gamma CDC6 molecule between the organic and aqueous phases was observed as being a function of surfactant concentration in the continuous phase. This partitioning was related to the formation of very small aggregates of the order 10 to 20 nm, probably Pluronic F68/gamma CDC6 mixed micelles as evidenced by the micrographs obtained by TEM. In the case of the nanospheres loaded with progesterone, the partitioning of the drug between the dispersed phase containing the cyclodextrin and the continuous aqueous phase containing Pluronic F68/gamma CDC6 aggregates was also demonstrated. The drug content found in the final nanospheres ranged from 4 to 5% (w/w) of the carrier. Finally, dilution experiments were carried out to evaluate the stability of the drug particle association. (C) 1998 Elsevier Science B.V. All rights reserved.