卡拉胶与几种亲水凝胶聚合物控制药物释放行为的比较

Comparison of Controlled-release Performance between Carrageenan and Several Other Hydrophilic Polymers

目的本研究主要是比较3种规格的卡拉胶(Viscarin®GP-209,Gelcarin®GP-379和Gelcarin®GP-911)与几种常见亲水凝胶骨架材料(羟丙甲纤维素,聚氧乙烯,海藻酸钠)控制药物释放的行为,以期为缓释制剂研发者选择骨架材料时提供一些思路。方法本研究以盐酸二甲双胍和茶碱作为模型药物,分别以上述聚合物作为亲水凝胶骨架材料制备缓释片,测定缓释片在不同介质中的药物释放,以考察聚合物对上述不同溶解度药物的释放度的影响。结果对于高水溶性药物模型药盐酸二甲双胍,Viscarin®GP-209可以达到良好的控制药物释放的效果,药物的主要释放机理为扩散,与其他几种聚合物类似。对于微溶性模型药茶碱,Gelcarin®GP-379控制药物为近零级释放,主要释放机理为溶蚀,而其他几种聚合物片剂中,茶碱为非Fickian扩散,主要释放机理为溶蚀与扩散共同控制。结论Gelcarin®GP-911由于其较强的膨胀和崩解作用不宜单独作为骨架材料使用,Viscarin®GP-209和Gelcarin®GP-379可以作为候选亲水凝胶骨架材料单独使用,对于某些药物可获得零级药物释放。

OBJECTIVES To compare the controlled-release performance of three types of carrageenan(Viscarin®GP-209,Gelcarin®GP-379 and Gelcarin®GP-911)with other common hydrophilic polymers(hydroxypropyl methylcellulose,poly oxyethylene and sodium alginate)and provide some ideas for the formulators to choose suitable polymers during developing controlled release(CR)tablets.METHODS Metformin hydrochloride and theophylline were selected as the model drugs and modified release tablets were prepared with the above polymers respectively to investigate the effect of polymers and drug properties on drug release.The performance of the polymer′s swelling and erosion were investigated by putting the pure polymer tablets in different medium.RESULTS For freely soluble drugs metformin,lambda type carrageenan Viscarin®GP-209 formed a viscous layer quickly and controlled drug release from the layer slowly.The main drug release mechanism of metformin prepared with Viscarin®GP-209 was diffusion which is the same as tablets with studied hydroxypropyl methylcellulose,poly oxyethylene or sodium alginate.For slightly soluble drug theophylline iota type Gelcarin®GP-379 retarded drug release more effectively than lambda type Gelcarin®GP-209.Gelcarin®GP-379 provided zero order drug release by erosion for theophylline while the other studied polymers controlling drug release by non-Fickian diffusion mechanism.CONCLUSION Gelcarin®GP-911 alone is not a suitable matrix polymer due to its strong swelling and disintegration.Viscarin®GP-209 and Gelcarin®GP-379 can be used as a candidate hydrophilic matrix polymer which could provide zero order drug release for some active pharmaceutical ingredient(API).