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 fro m an amphiphilic 2,3-di-O-hexanoyl-gamma-cyclodextrin (gamma CDC6) usi ng the emulsification solvent evaporation method. This preparation met hod consists in emulsifying an organic phase containing the cyclodextr in in an aqueous phase containing Pluronic F68 as surfactant. The infl uence of the process parameters, i.e. surfactant concentration and ini tial gamma CDC6 content, on the characteristics of nanosphere preparat ion, as well as on the nanosphere loading of a hydrophobic drug, proge sterone, was evaluated. Cyclodextrin nanospheres presenting a mean dia meter 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 th e 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 p artitioning was related to the formation of very small aggregates of t he 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 na nospheres loaded with progesterone, the partitioning of the drug betwe en the dispersed phase containing the cyclodextrin and the continuous aqueous phase containing Pluronic F68/gamma CDC6 aggregates was also d emonstrated. The drug content found in the final nanospheres ranged fr om 4 to 5% (w/w) of the carrier. Finally, dilution experiments were ca rried out to evaluate the stability of the drug particle association. (C) 1998 Elsevier Science B.V. All rights reserved.