愈创木酚甘油醚缓释片不同湿度下颗粒的流动性变化与片剂质量间的关系

Relationship between Granule Flowability under Different Humidity and Quality of Guaifenesin Sustained Release Tablet

目的考察环境湿度对愈创木酚甘油醚缓释片颗粒流动性的影响,探求颗粒流动性变化和片剂质量之间的关系,为该品种的工业化生产提供依据。方法对颗粒的吸湿性进行初步研究,求取颗粒的临界相对湿度(CRH)。以0 d的颗粒和片剂为参比,考察颗粒暴露在RH 33%、60%、75%、84%、92.5%下10 d后流动性的变化,测量相应颗粒制得的片剂的质量指标,探讨颗粒流动性变化与片剂质量之间的关系。结果颗粒的CRH在RH 67%～68%之间。在湿度高于RH 60%下10 d后,颗粒流动性、水分含量、片剂的外观、片重差异极值、脆碎度都有明显改变。以颗粒的压缩度(X1)、休止角(X2)为自变量,片重差异极值(Y1)、脆碎度(Y2)为因变量进行二元回归分析得:Y1=0.192X1+0.092X2-7.398(r=0.992 1),Y2=0.069X1+0.087X2-3.505(r=0.988 1),P<0.001时,在观测范围内具有统计学意义。结论颗粒的生产和储存的环境湿度应小于RH60%,颗粒的休止角和压缩度与片剂的质量指标(片重差异极值、脆碎度)间存在统计学意义上的函数关系。

OBJECTIVE To study influence of humidity on granule flowability, explore relationship between flowability and quality of guaifenesin sustained tablet, give a basis for industrialization.METHODS By hygroscopicity study, CRH was measured. After 10 days in RH 33%、60%、75%、84%、92.5%, flowability of granule and quality index of tablet, such as appearance、extremum of weight、friability was measured and compared with result of 0 d. Functional relationship between micromeritics parameter and quality index of tablet was fitted. RESULTS CRH of granule is between RH 67%-68%. When relative humidity is above RH 60%, flowability and quality of tablet is changed obviously. Used compressbiliity as X1, repose angle as X2, extremum of tablet weight as Y1, friability as Y2, linear relationship of them is Y1=0.192X1＋0.092X2-7.398（r=0.992 1）,Y2=0.069X1＋0.087X2-3.505（r=0.988 1）,when P〈0.001, the equations had statistical significance in the range of observation. CONCLUSION Relative humidity of production and storage of granule should less than RH 60%. Functional relationship between micromeritics parameter of granule（compressbiliity and repose angle） and quality index of tablet（extremum of weight、friability）had statistical significance in the range of observation.