Complexation of ebastine with beta-cyclodextrin derivatives

Autores: Maddens, T.; Vélaz Rivas, Itziar; Machín Ledesma, Rubén; Isasi Allica, José Ramón; Martín Bachiller, Carmen; Martínez Oharriz, María Cristina; Zornoza Cebeiro, Arantza
ISSN: 1388-3127
Volumen: 70
Número: 3 - 4
Páginas: 415 - 419
Fecha de publicación: 2011
Lugar: WOS
Complexation of ebastine (EB) with hydroxypropyl and methyl-beta-cyclodextrin (HP-beta-CD and Me-beta-CD) was studied in aqueous solutions and in the solid state. The formation of inclusion complexes in aqueous solutions was analysed by the solubility method. The assays were designed using low CD concentrations compared with the solubility of these derivatives in order to avoid non-inclusion phenomena and to obtain a linear increase in EB solubility as a function of CD concentration. The values of complexation efficiency for HP-beta-CD and Me-beta-CD were 1.9 x 10(-2) and 2.1 x 10(-2), respectively. It seems that the non polar character of the methyl moiety slightly favoured complexation. In relation to solid state complexation, 1: 1 EB: CD systems were prepared by kneading, and by heating a drug-CD mixture at 90 degrees C. They were analysed using X ray diffraction analysis by comparison with their respective physical mixtures. A complex with a characteristic diffraction pattern similar to that of the channel structure of beta-CD was formed with Me-beta-CD in 1: 1 melted and 1: 2 EB: CD kneaded systems. Complexation with HP-beta-CD was not clearly evidenced because only a slight reduction of drug crystallinity was detected. Finally, the loading of EB in two beta-CD polymers cross-linked with epichlorohydrin yielded 7.3 and 7.7 mg of EB/g polymer respectively.