Grafting β-cyclodextrins to silicone, formulation of emulsions and encapsulation of antifungal drug

Abstract

Emulsions of silicone polymers having β-cyclodextrin units as lateral chains have been prepared and used for the encapsulation of the antifungal drug griseofulvin. Such technology enables the formulation of active substances that are not soluble in water as dosage forms for topical administration. Chemical grafting of monoallyl derivative of β-cyclodextrins to poly(methylhydr osiloxane) polymer or to poly(methylhydrosiloxane-co-dimethylsiloxane) copolymer through hydrosilylation reaction was investigated. Grafting of β-cyclodextrins to the Si-H units was limited by steric hindrance of the bulky cyclic D-heptaglucopyranoside. Therefore the kinetics of the grafting reaction slowed down dramatically as the conversion increased. The way to achieve high grafting rates was to run the grafting reaction for a very long time. The full conversion of the poly(methylhydrosiloxane) homopolymer could not be reached. The grafted silicone polymers have been emulsifi ed by the "spontaneous emulsifi cation" method. The emulsifi cation took advantage of the very low solubility of the polymers in water. Stable emulsions with sizes ranging between 200 and 500 nm have been produced. The emulsions of β-cyclodextrins grafted on silicone could encapsulate the antifungal substance griseofulvin inside the β-cyclodextrin cavity by formation of inclusion complex. The encapsulation rate was limited to the 1:1 stoichiometry of the complex. Supplementary amount of griseofulvin slowly precipitated as crystalline particles in the aqueous phase. There are several benefi ts of using a silicone polymer with grafted β- cyclodextrin units. The silicone backbone is biocompatible and adherent to the skin. Grafted β-cyclodextrin units enable the incorporation of griseofulvin in silicone oil. Lastly, the encapsulation of griseofulvin as inclusion complexes during the "spontaneous emulsifi cation" process is quite easy. Let us recall that the formation of an inclusion complex of griseofulvin and the water-soluble β-cyclodextrin is a very diffi cult task owing to the low solubility of griseofulvin in water. © 2008 Springer Science+Business Media B.V.