چکیده (انگلیسی):

The objective of the present study was to optimize the con-centration of a chitosan solution, stirring speed, and concen-tration of drugs having different aqueous solubility for the formulation of chitosan microspheres. Chitosan micro-spheres (unloaded and drug loaded) were prepared by the chemical denaturation method and were subjected to meas-urement of morphology, mean particle size, particle size distribution, percentage drug entrapment (PDE), drug load-ing, and drug release (in vitro). Morphology of the micro-spheres was dependent on the level of independent process parameters. While mean particle size of unloaded micro-spheres was found to undergo significant change with each increase in concentration of chitosan solution, the stirring rate was found to have a significant effect only at the lower level (ie, 2000 to 3000 rpm). Of importance, spherical unloaded microspheres were also obtained with a chitosan solution of concentration less than 1 mg/mL. Segregated unloaded microspheres with particle size in the range of 7 to 15 μm and mean particle size of 12.68 μm were obtained in the batch prepared by using a chitosan solution of 2 mg/mL concentration and stirring speed of 3000 rpm. The highest drug load (μg drug/mg microspheres) was 50.63 and 13.84 for microspheres containing 5-fluorouracil and meth-otrexate, respectively. While the release of 5-fluorouracil followed Higuchi’s square-root model, methotrexate re-leased more slowly with a combination of first-order kinet-ics and Higuchi’s square-root model. The formation of chi-tosan microspheres is helped by the use of differential stir-ring. While an increase in the concentration of water-soluble drug may help to increase PDE and drug load over a large concentration range, the effect is limited in case of water-insoluble drugs.