pH响应型肠道定位缓释阿司匹林微丸的制备和性能

Preparation and properties of pH responsive enteric site-specific sustained-release aspirin pellets

定位缓释制剂可减少药物对人体正常组织的毒性及不良反应,提高药物的生物利用度。长期频繁的服用阿司匹林对胃肠道影响很大,将其制成具有pH响应性的肠道缓释制剂,可降低阿司匹林对胃黏膜的刺激。本实验通过向海藻酸钠(Na-Alg)溶液中加入不同比例的羧甲基壳聚糖(CMCs),并采用滴注法将其滴入不同浓度的CaCl2溶液中离子交联固化制备成海藻酸钙(Ca-Alg)和CMCs组合而成的CMCs#Ca-Alg互穿网络凝胶丸,经分离、干燥后形成CMCs#Ca-Alg互穿网络微丸。通过观察微丸的形貌和测定、分析微丸的稳定性、溶胀情况、药物释放情况,发现:所制备干燥微丸直径为0.5~1 mm,CMCs的加入提高了CMCs#Ca-Alg微丸的形态稳定性、热稳定性,降低了其溶胀度,降低了药物释放量,有利于微丸中药物的缓释;且当CMCs与Na-Alg的质量配比为1:4时,使用浓度为1%的CaCl2溶液固化时,微丸的形态稳定性最好,药物释放性能符合12 h缓释制剂的释放度要求。所制备的肠道定位缓释阿司匹林微丸有望作为口服类抗血栓药物制剂。

Localization of sustained-release preparations can reduce the toxic and side effects of drugs on normal tissues and improve the bioavailability of drugs.Long-term and frequent administration of aspirin has a great impact on the gastrointestinal tract,so it can be made into a pH-responsive intestinal sustained-release preparation,which can reduce the irritation of aspirin to the gastric mucosa.In this experiment,different proportions of carboxymethyl chitosan(CMCs)were added to sodium alginate(Na-Alg)solution,and then dropped into different concentrations of CaCl2 solution by using the dripping method to prepare CMCs#Ca-Alg interpenetrating network gel pills,which were prepared by combining calcium alginate(Ca-Alg)and CMCs.CMCs#Ca-Alg interpenetrating network pellets were formed after separation and drying.By observing the morphology of pellets,measuring and analyzing the stability,swelling and drug release of pellets,it is found that:The prepared dry pellets were 0.5-1 mm in diameter.The addition of CMCs improved the morphology and thermal stability of CMCs#Ca-Alg pellets,reduced the swelling degree and drug release,which was beneficial to the slow release of drugs in the pellets.In addition,when the mass ratio of CMCs and Na-Alg was 1:4 and the concentration of 1%CaCl2 solution was used for curing,the morphology stability of pellets was the best,and the drug release performance met the release requirement of 12 h sustained release preparation.The prepared intestinal localization sustained release aspirin pellets are expected to be used as oral antithrombotic drug preparations.