Polymer-lipid based mucoadhesive microspheres prepared by spray-congealing for the vaginal delivery of econazole nitrate

This research aimed to evaluate a new approach for the preparation of mucoadhesive microparticles and to design an innovative vaginal delivery systems for econazole nitrate (ECN) able to enhance the drug antifungal activity. Seven different formulations were prepared by spray-congealing: a lipid-hydrophilic matrix (Gelucire (R) 53/10) was used as carrier and several mucoadhesive polymers such as chitosan, sodium carboxymethylcellulose and poloxamers (Lutrol (R) F68 and F127) were added. All microparticles were characterized and compared for morphology, particle size, drug loading and solubility in simulated vaginal fluid, bioadhesion to mucosal tissue, dissolution behaviour and for their physicochemical properties. The antifungal activity of the microparticles against a strain of Candida albicans ATCC 10231 was also investigated. Non-aggregated microspheres with high yields (>90%, w/w) and with prevalent size in the range 100-35S mu m were obtained. Both poloxamers significantly (p < 0.01) improved the solubility and in vitro bioavailability of the low solubility drug and the mucoadhesive strength. Poloxamers/Gelucire (R)-based microparticles exhibited an inhibition effect on the C. albicans growth, suggesting their use as an effective treatment for vaginal candidiasis, with potential for reduced administration frequency. In conclusion the results demonstrated that spray-congealing technology can be considered a novel and solvent-free approach for the production of mucoadhesive microparticles for the vaginal delivery of ECN. (c) 2008 Elsevier B.V. All rights reserved.