Preparation Of Chitosan Microspheres By Emulsion Cross-linking Method And Study Of Drug Loading

The microsphere as the new dosage form is very useful in the pharmaceutical field. It has lots of advantages, such as increasing the drug performance, and decreasing the administration frequency. Especially the chitosan microsphere, shows up much recently. The chitosan's resource is natural, wide and economic, morphology of the microspheres is spheroid and good.In this paper, we prepared the chitosan microspheres by emulsion cross-linking method and evaluated its drug loading by 5-Fu and BSA.In preliminary experiment, we picked out the chitosan with 1×105MW as the base material, liquid paraffin as the oil phase, and the glutaraldehyde saturated toluene (GST) as the cross-linking agent. In the experiment of preparation chitosan microspheres entrapping 5-Fu (5-Fu-MS), we investigated 9 factors which affect the microspheres'quality, and we had the results as follow. The diameter of the microspheres is in inverse ratio with the concentration of HAc, oil/water phase volume, stirring speed, and emulsion time. The diameter of the microspheres is in direct ratio with the concentration of chitosan solution and amount of cross-linking agent. The amount of drug, cross-linking time and temperature has little effect on the diameter of the microspheres. On the other side, the drug loading efficiency is in direct ratio with the diameter of the microspheres and the amount of drug. From the results of release experiment, cross-linking temperature has more important effect on the extent of cross-linking than cross-linking time. According to the best experiment condition, we obtained the 5-Fu-MS with the diameter 2.3μm, the size distribution 2~19μm, DL 10.2±0.02% and LE 32.5%.Emulsion cross-linking method was used in preparation of BSA microspheres with active drug loading, protein protective agent trehalose didn't take the protective role, and BSA was denatured, the microspheres'morphology was poor. BSA microspheres with passive drug loading were also bad. Their DL and LE were 2.29±0.28% and 9.15±0.37%, respectively.