Preparation and evaluation of sustained release cross-linked chitosan microspheres containing phenobarbitone
Preparation and evaluation of sustained release cross-linked chitosan microspheres containing phenobarbitone
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DOI：
10.3109/02652049809006864
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发表时间：
1998-05-01
影响因子：
3.9
通讯作者：
Al-Dardari, MM
中科院分区：
文献类型：
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作者：
Al-Helw, AA;Al-Angary, AA;Al-Dardari, MM
以脱水山梨糖醇单油酸酯为稳定剂，将壳聚糖的醋酸水分散液在轻质液体石蜡中进行戊二醛交联，成功制备了苯巴比妥壳聚糖微球。根据制备条件的不同，可以制备出粒径均匀、球形的微球，载药量最高可达57.2%。影响微球制备和性能的主要因素是壳聚糖的分子量、浓度以及所用稳定剂的浓度。发现当微球与溶解介质接触时，将柠檬酸掺入微球中增加了水溶性凝胶的形成，从而增加了药物释放速率。通过使用较低浓度的壳聚糖（1.0%w/v）和低分子量壳聚糖，随着脱水山梨醇单油酸酯浓度的增加（高达4.0%w/v），粒径向更小的直径方向移动。在所有制备的微球中显示出快速的初始药物释放（掺入药物的20-30%），随后缓慢释放剩余量的药物。高分子量壳聚糖微球的释药速率比中、低分子量壳聚糖微球慢。高浓度的脱水山梨糖醇单油酸酯增加药物释放速率。
Chitosan microspheres containing phenobarbitone were successfully prepared by glutaraldehyde cross-linking of an aqueous acetic acid dispersion of chitosan in light liquid paraffin containing sorbitan mono-oleate as a stabilizing agent. Uniform and spherical microspheres, with a loading efficiency up to 57.2%, could be prepared depending on the preparation conditions. The main parameters affecting the preparation and the performance of the prepared microspheres were the molecular weight and concentration of chitosan as well as the concentration of the used stabilizing agent. The incorporation of citric acid into the microspheres was found to increase the formation of a water-soluble gel when the microspheres come in contact with the dissolution medium increasing the rate of drug release. The particle size was shifted towards smaller diameters with increased concentration of sorbitan mono-oleate, up to 4.0% w/v, by use of a lower concentration of chitosan (1.0% w/v) and chitosan with low molecular weight. Rapid initial drug release (20-30% of the incorporated drug) was exhibited in all the prepared microspheres followed by slow release of the remaining amount of the drug. The release rate of the drug from the microspheres prepared from high molecular weight chitosan was slow in comparison with that prepared from medium and low molecular weight chitosan. High concentrations of sorbitan mono-oleate increased the rate of drug release.