Hydrogel à base de chitosane-xanthane une matrice pour l'inclusion et le relargage de médicaments

Abstract

Drug solubility has been a common limitation for the development of new drug formulations. Several mechanical and chemical approaches have been used in order to enhance the dissolution rate of water insoluble drugs, and consequently produce an increase of their bioavailability. This work deals with a hydrogel system prepared with two natural polymers, chitosan and xanthan. The main goal for this research was to explore whether this highly hydrophilic hydrogel can be effectively used as matrix to enhance the solubility of water insoluble drugs, and subsequently, determine the potential of the drug-hydrogel system as a vehicle for controlled release. A two-step method was developed for preparing the drug-hydrogel systems. The process consisted of: (i) the formation of a homogenous dispersion of the drug in the xanthan solution; and (ii) the formation of the hydrogel by the complexation of xanthan with chitosan. As drug models, four water insoluble compounds were used: fenofibrate, ursodeoxycholic acid, nifedipine and indomethacin. The drug content in the freeze-dried hydrogels varied from 15 to 45% (w/w), and was adjusted by the amount of drug added during preparation. Dissolution tests showed that the incorporation of the drug in the hydrogel network modified the dissolution profiles. The drug release rate was found to be independent of the drug content, but dependent of the chitosan molecular weight. The effect of the molecular weight was related to the network structure of the chitosan-xanthan hydrogel, the hydrophilicity of the matrix, and the crystallinity of the drug particles.