异福片制粒工艺改进

Improvement of Granulation Technology of Rifampin and Isoniazid Tablets

目的:对异福片制粒工艺进行改进,以解决制粒中粉尘污染严重的问题。方法:选用聚乙二醇(PEG)、共聚维酮为黏合剂,采用熔融制粒工艺制备片剂;以脆碎度、溶出度等为考察指标筛选处方;采用高效液相色谱法对制剂中利福平、醌式利福平、N-氧化利福平、利福霉素SV和异烟腙5种物质的含量进行测定,选择3批新方法和2批原干法制粒工艺产品进行影响因素试验和稳定性试验,比较其中的5种物质的含量变化。结果:优选处方以PEG600080mg、共聚维酮10mg为黏合剂,交联聚乙烯吡咯烷酮(PVPP)20mg为崩解剂,70℃沸腾干燥。所制制剂脆碎度0.39%,溶出度利福平78.55%、异烟肼87.92%。利福平检测质量浓度在0.2～20mg/L内,醌式利福平、利福霉素SV、N-氧化利福平和异烟腙检测质量浓度在0.2～10mg/L内均与其峰面积呈良好的线性关系,回收率为99.5%～100.4%,RSD为0.98%～2.11%(n=9)。与原干法产品比较,新工艺在考察条件内5种物质的含量增长情况均基本一致。结论:采用熔融制粒工艺能有效减少粉尘污染,所制产品与原工艺产品质量相当。

OBJECTIVE：To improve granulation technology of Rifampin and isoniazid tablets,and to solve the problem of dust pollution in granulation.METHODS：The tablets were prepared by melting granulation method using polyethylene glycol（PEG）and copolyvidone as adhesive;the formulation was screened using friability and dissolution rate as index.The contents of rifampicin,rifampicin quinone,N-oxide rifampicin,rifamycin SV and isoniazone were determined by HPLC.Influential factor test and stability test were conducted with 3 batches by new methods and 2 batches by original dry granulation.The contents of 5 kinds of substance were compared.RESULTS：The optimal formulation was as follows：PEG6000 80 mg and copolyvidone 10 mg as adhesive,crospolyvinylpyrrolidone（PVPP）20 mg as disintegrants,fluidizing drying at 70 ℃.The friability of prepared tablets was 0.39%,and the dissolution rate of rifampin was 78.55% and that of isoniazid was 87.92%.The linear range of rifampin was 0.2-20 mg/L,and linear ranges of rifampicin quinone,rifamycin SV,N-oxide rifampicin and isoniazone were 0.2-10 mg/L.Their recoveries were 99.5%-100.4% with RSD of 0.98%-2.11%（n=9）.Compared with original dry granulation,the growth of 5 kinds of substances were similar basically by new technology.CONCLUSIONS：The melting granulation technology can reduce dust pollution efficiently;the quality of prepared tablets using two methods has no obvious changes.