Tyrosol and caffeic acid are biophenols that contribute to the beneficial properties of virgin olive oil. The influence of hydroxypropyl-beta-cyclodextrin (HP beta-CD) on their respective antioxidant capacities was analyzed. The ORAC antioxidant activity of tyrosol (expressed as mu M Trolox equivalents/mu M Tyrosol) was 0.83 +/- 0.03 and it increased up to 1.20 +/- 0.11 in the presence of 0.8 mM HP beta-CD. However, the ORAC antioxidant activity of caffeic acid experienced no change. The different effect of HP beta-CD on each compound was discussed. In addition, the effect of increasing concentrations of different cyclodextrins in the development of ORAC-fluorescence (ORAC-FL) assays was studied. The ORAC signal was higher for HP beta-CD, followed by M beta-CD, beta-CD, gamma-CD and finally alpha-CD. These results could be explained by the formation of inclusion complexes with fluorescein.

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.

beta-cyclodextrin insoluble polymers (beta CDP), a type of hydrogels with a high swelling capacity, can be obtained by crosslinking beta-cyclodextrin (beta CD) with epichlorohydrin. Terbinafine (TB) is an oral and topical antifungal drug that can be housed into the cavity of beta-cyclodextrin, so it seems probable that the drug could interact with the insoluble beta CDP. Different organic molecules can be sorbed on the polymer network and also included within the beta CD cavities, so these hydrogels have potential applications in the pharmaceutical field as drug carriers. In this work, the sorption of TB on beta CDP and the optimal conditions to load the polymer with the drug were studied. Sorption kinetics and Freundlich isotherms of TB on beta CDP at 25A degrees C were obtained and the influence of several parameters on the sorption process of TB was investigated. It was found that a high initial concentration of drug, high TB:beta-CD molar ratios and low ionic strengths were the most favourable conditions. No significant influence of temperature was observed. Moreover, the sorption kinetic profile obtained for terbinafine was compared to that of naftifine, another antifungal agent of similar structure. Terbinafine presented higher affinity for the polymer, according to the higher stability constant of the drug-beta CD inclusion complex. In relation to the release studies from the loaded polymer, 0.1 M HCl was the most favourable medium to allow the release of the drug.

The mechanisms of sorption and release of solutes from polymeric materials synthesised by cross-linking ß-cyclodextrin (ß-CD) with epichlorohydrin have been investigated. Gemfibrozil (pKa 4.7) was chosen as model solute. The polymers were obtained by suspension (P1) and block polymerisation (P2). Both P1 and P2 had similar ß-CD contents (65 and 64%) and their swelling capacities were 5.0 and 5.8 cm3/g, respectively. The sorption of gemfibrozil kinetic data in water and in aqueous solutions at pH 2.8 and 7.0 were fitted to a hyperbolic equation and they were studied by applying the Weber and Morris and the Elovich equations. P2 presented faster rates and higher sorption capacities in water and at pH 2.8. The mechanisms of sorption were pH-dependent. In water, the sorption rate was determined by the diffusion of gemfibrozil in the polymer network and fitted the Weber and Morris equation. At pH 2.8 a better adjustment to the Elovich equation suggested a significant influence of the inclusion in the ß-CD cavities. The release kinetics at pH 7.0 was controlled by drug solubilisation and presented maximum release values of 90 (P1) and 95% (P2), with a suitable regeneration of the loaded polymer. In water, the release was slower, fitted a hyperbole and the mechanism was controlled by drug solubility and also by the polymeric geometry. Finally, release assays were carried out from discs of loaded polymer in a medium that simulated the gastrointestinal tract.

Terbinafine (TB) is an allylamine derivative used as oral and topical antifungal agent. The physicochemical properties of the complexes between TB and different cyclodextrins (CDs): alpha-CD, beta-CD, hydroxypropyl beta-CD, methyl beta-CD and gamma-CD, have been studied in pH 12 aqueous solutions at 25 A degrees C and in the solid state. Different phase solubility profiles of TB in the presence of CDs have been obtained: A(L) type for TB with hydroxypropyl beta-CD and gamma-CD, A(P) type for the complexes with methyl beta-CD and alpha-CD, while a B(S) profile was found for TB-beta-CD. The apparent stability constants of the complexes were calculated at 25 A degrees C from the phase solubility diagrams. The higher increase of TB solubility, up to 200-fold, together with the higher value of the stability constant were found for the complex with methyl beta-CD. Solid systems of 1:1 drug:CD molar ratio were prepared and characterised using X-ray diffraction patterns, thermal analysis and FTIR spectroscopy. The coevaporation method can be considered the best method in preparing these solid complexes. The complexes of TB with natural CDs, except with alpha-CD, were crystalline, whereas the methyl and hydroxypropyl derivatives gave rise to amorphous phases. Dissolution rate studies have been performed with TB-beta-CD and TB-HP beta-CD complexes, showing a positive influence of complexation on the drug dissolution.