Dissolution and permeation properties of naproxen from solid-state systems with chitosan

The purpose of this study was to investigate the influence of different types of chitosan and of the preparation technique of the drug-polymer combination in improving the dissolution and permeation abilities of naproxen, a very poorly water-soluble anti-inflammatory drug. Drug-chitosan systems were prepared by simple physical mixing, kneading, cogrinding, or coevaporation using five types of chitosan (base and glutamate or hydrochloride salts, both at two different molecular weights). The products were tested for drug-dissolution behavior and for permeation properties through both Caco-2 cell monolayers and artificial lipophilic membranes. All combinations with chitosan base were significantly (P<.01) more effective in enhancing drug-dissolution rate than those with both its salts, probably in virtue of its higher amorphizing effect toward the drug, as observed in solid-state studies. A different rank order was found in permeation experiments in which chitosan glutamate was the most powerful partner in improving the drug-apparent permeability (p<.01), followed by the hydrochloride salt (p<.05), whereas no significant effect was obtained with chitosan base. Cogrinding was the most powerful technique in promoting both dissolution and permeation properties of the drug, thus pointing out the importance of the preparation method in obtaining efficacious drug-carrier systems. Finally, the good correspondence between permeation experiments with Caco-2 cells and those with the artificial lipophilic membrane indicated the suitability of this latter in preformulation studies for a rapid screening of the best carrier and the most efficient drug-carrier preparation method for improving the biopharmaceutical properties of drugs.