Preparation Of Nifedipine-loaded Chitosan Sustained Release Microsphere

Nifedipine is most commonly used as the antianginal and antihypertensive medicine. However, it has high crystallization, poor solubilization and photosensitive property, and the rate of adverse effects of its normal reagent is high, so stable and sustained release nifedipine formulations have attracted much attention. Chitosan is a biodegradable natural polymer with great potential for pharmaceutical applications due to its degradability, biocompatibility, and nontoxicity. Chitosan as the carrier can not only improve the solubilization of poorly soluble drugs, but also control the release of drugs Therefore, in this paper, nifedipine-loaded chitosan microspheres were prepared to enhance the stability and reduce the adverse effect of nifedipine.The conditions of the preparation of chitosan microspheres using emulsion-crosslinking method were investigated by the orthogonal and single factor experiments. The optimal preparation conditions were as follows: chitosan solution with certain concentration, 20ml; liquid paraffin containing 4% Span-80, 30ml; glutaraldehyde, the ratio of amino and aldehyde is 1:1; stirring speed, 350 rpm; reaction time, 30 min.Pre-crosslinking method, which is an improvement of the emulsion-crosslinking method, was then developed to prepare the chitosan microspheres. The optimum conditions were as follows: chitosan solution of certain concentration, 20ml; liquid paraffin with 6% Span-80 content emulsion-crosslinking method, 30ml; stirring speed, 350 rpm; glutaraldehyde, the ratio of amino and aldehyde is 1:1. In this experiment, 5% of glutaraldehyde was used as pre-crosslinking agent. After ultrasonic dispersed 5 min, to the solution was added the residual crosslinking agent and reacted for 30 min. Results showed that the microspheres made by pre-crosslinking had good appearance and uniform size.The methods of detection and analysis of were established and 0.5% SDS solution was selected to determine the amount of nifedipine released from the microspheres, in which the solubility of nifedipine was detected.Finally, nifedipine-loaded chitosan microspheres were prepared, and their particle size, appearance, entrapment efficiency, drug loading and in vitro release were also studied. Results indicated that, compared with the emulsion-crosslinking method, the microspheres prepared by the pre-crosslinking method had better performance in balling property, entrapment efficiency, drug loading and in vitro release. When the concentration of the chitosan was 1.0%, the entrapment efficiency was 32.1%, the drug loading was 8.5%, and the in vitro released drug content was 44.2% after 12h and 88.5% after 48h; and it means that the entrapment efficiency of the microspheres increased 3%, the drug loading increased 1%, and in vitro released drug content after 48h increased 12%.