Hydrogel matrices containing single and mixed natural cyclodextrins. Mechanisms of drug release

Abstract

Hydrogel networks of α, β or γ-cyclodextrin (CD) and mixtures of α/β or β/γ CDs have been obtained using epichlorohydrin (EP) as a crosslinking agent. Discs of the resulting polymers were evaluated as drug carriers for controlled release using the antiinflammatory naproxen (NAP) as a model drug. βCD polymer (βCDP) has shown the highest amount of drug loaded and the lowest one corresponds to the polymer containing αCD, in agreement with the affinities of NAP for the corresponding cyclodextrins.In addition, in vitro drug release kinetics assays from the loaded discs have been carried out. The different release profiles at simulated physiological conditions of pH and temperature have been correctly defined, identifying in each case the release mechanisms. Using suitable mathematical models, the apparent diffusional coefficients and the corresponding kinetic parameters have been calculated. It can be inferred that a simple Fickian diffusion mechanism occurs, except for the mixed polymers at pH 1.2 (anomalous transport) and in the case αCDP at pH 7.0 (burst phenomenon). Furthermore, the diffusion and relaxation contributions have been determined for the mixed polymers in order to achieve progress in the design of new polymer matrices according to the structure of the selected drugs.