Preparation of Supramolecular Hydrogels Containing Poloxamers and Methyl-β.-cyclodextrin

Abstract

Meloxicam is a non-steroidal anti-inflammatory drug used in the treatment of rheumatoid arthritis, osteoarthritis and other inflammatory diseases. However, its prolonged use is associated to several side effects like gastrointestinal perforations, ulcerations and bleeding, probably due its low aqueous solubility and wettability after oral administration. These side effects can reduce patient compliance and discourage physician from prescribing this drug. In this way, inclusion complexes between meloxicam and methyl-β-cyclodextrin were prepared in aqueous solution by phase solubility studies and in solid state by freeze-drying method in order to increase drug solubility. The physicochemical characterization of the prepared complexes in solid state was performed by different techniques. Furthermore, hydrogels containing poloxamers were prepared for topical administration of meloxicam. For this purpose, solid inclusion complexes were incorporated in hydrogels with different poloxamers composition. The rheological behaviour of these formulations was studied by different methods and the drug release from optimised hydrogels was evaluated by Franz diffusion cells, applying some mathematical models to analyse the drug release mechanism from hydrogels. Results from phase solubility studies showed the formation of inclusion complexes between meloxicam and methyl-beta-cyclodextrin in aqueous solution in a 1:1 stoichiometry and an increase in drug solubility. Different techniques employed indicated complete formation of complexes in solid state prepared by the freeze-drying method. Moreover, the performed set of rheological studies, easily adapted to similar systems, demonstrated that hydrogels containing poloxamers and cyclodextrin may provide a suitable supramolecular platform for meloxicam delivery as a novel strategy to increase drug bioavailability. Keywords: Controlled release, Hydrogels, Inclusion Complexes, Meloxicam, Methyl-β-cyclodextrin, Poloxamers.