pH非依赖性释放缓释片的研制

Studies on pH independent sustained release tablets

目的：制备ｐＨ 非依赖性释放缓释片，使药物在体内的释放不因所处胃肠道不同区段的ｐＨ 不同而发生变化。方法：以盐酸奈福泮为模型药物，考察了以壳聚糖和海藻酸钠为基质对药物释放的影响，并通过红外光谱考察药物释放机制。结果：单用壳聚糖或海藻酸钠为缓释基质，其体外释放呈ｐＨ 依赖性；两者合用能明显降低缓释片体外释放对ｐＨ 的敏感性，且当壳聚糖海藻酸钠以１∶２ 混合使用时，缓释片呈体外ｐＨ 非依赖性释放的特征。在不同释放介质中，壳聚糖和海藻酸钠互为骨架。结论：采用合适的基质组方可以制备ｐＨ 非依赖性释放缓释片。

OBJECTIVE:To prepare pH independent sustained release tablets (SRTs), with expect to drug release not being influenced by the different pH in the gastrointestinal tract.METHOD:Nefopam hydrochloride (NFP) was used as the model drug to investigate the effect of chitosan (CS) and sodium alginate (NaAlg) on the drug release from SRTs. The drug release mechanism of the tablet was investigated by FT IR.RESULTS:The release of NFP from SRTs was pH dependent when CS or NaAlg was used separately . The drug release sensitivity of SRTs to pH of the dissolution medium would be decreased if the two retarding agents were used together. Furthermore, the release rate would be independent to pH if the ratio of CS to NaAlg was adjusted to 1∶2. The content of retarding component in pH independent SRTs had no effect on the release profiles of SRTs. The drug release rate of SRTs could be further adjusted by adding diluents. FT IR showed that, at the acidic pH, NaAlg was the matrix component of SRTs and the drug release was accompanied with the gelation and dissolution of CS, and that at the basic pH, the action of the two retarding agents exchanged.CONCLUSION: The pH independent sustained release tablets can be prepared by using adequate combination of retarding agents.