一个计量型制剂含量均匀度检查新方案的制订与评价

FORMULATION AND EVALUATION OF A NEW CONTENT UNIFORMITY TESTING SCHEME BY VARIABLES

采用概率统计计算方法找到符台一定质量要求的制剂批单剂含量总体均值和标准差的轨迹,进行近似并确定了二次抽样范围,从而制订出一个以标示量为参考值、二次抽样的计量型含量均匀度检查新方案;然后用蒙特卡洛即统计模拟方法为该方案在4个不同允许废品率下绘制抽样特性(OC)曲线,同时统计平均样本容量,并与几个国家药典典型的含量均匀度检查法的对应指标比较;最后讨论了新方案的准确性、灵活性和在控制生产上的实用性等问题。

A new content uniformity testing scheme by variables for pharmaceutical preparation has been formulated in two steps: 1. The locus of the point (μ,σ) representing pairing of the two population variables of active ingredient in individual dosage units was found by statistical probability computation and approximated to two connecting lines, one circular segment and one straight line, the equations of which contain the two sample variables (?) and S; 2. Two straight lines delimiting a double sampling zone were found by weighing the two contradictory indices, high accuracy and small sample size of the sampling inspection scheme. The sample size in the initial inspection is n_1=10, while that in the second inspection is n=n_1+n_2=30. The 4 discriminants of the new scheme are as follows:A_1+k_1S_1=l, A_1 +k_2S_1 =lA_2+S_2=k_3, A+k_4S=l where l is the tolerant content limit of a dosage unit; k_1, k_2, k_3 and k_4 are parameters that depend on l; and other symbols are self--evident. The numbers of k_1,k_2, k_3, k_4 for±l%=±15% and d%≈8, 7, 6 and 5% are given, where d is the acceptance defective in lot.The algorithms used are outlined. Some of the merits of the new scheme——accuracy, adapta-bility and practicability——are discussed.