体外溶出度曲线比较：统计与分析，模型依赖方法。

In-vitro dissolution profile comparison: statistics and analysis, model dependent approach.

作者信息

Sathe P M, Tsong Y, Shah V P

机构信息

Office of Pharmaceutical Sciences, U.S. Food and Drug Administration, Rockville, Maryland 20855, USA.

出版信息

Pharm Res. 1996 Dec;13(12):1799-803. doi: 10.1023/a:1016020822093.

DOI:10.1023/a:1016020822093

PMID:8987074

Abstract

PURPOSE

To develop and propose a "model dependent' approach for the in-vitro dissolution profiles comparison.

METHODS

Diltiazem hydrochloride tablet dissolution profiles were compared using a statistical approach based on a mathematical model. A similarity region (SR) was defined based on the intra- and inter-lot parameter variances of the final production size standard lots. Statistical distances between the test and reference lot parameter means were computed and normalized. A 90% confidence region (CR) was developed around the statistical distance. The confidence region was compared with the similarity region to assess the similarity or dis-similarity of the test and reference (REF) lot dissolution profiles. Two test lots, one with a "minor' modification (mm) the other with a "major' modification (MM), were evaluated.

RESULTS

"Weibull' was selected as the "model' function. A comparison of the confidence regions around the statistical distance of "mm-REF' and "MM-REF' with the similarity region, suggested that the dissolution profiles of the "minor' modification lot were similar and that of "major' modification lot were dis-similar to the reference lot.

CONCLUSIONS

A "model dependent' approach was shown to be useful for the inter-lot in-vitro dissolution profiles comparison.

摘要

目的

开发并提出一种用于体外溶出度曲线比较的“模型依赖”方法。

方法

采用基于数学模型的统计方法比较盐酸地尔硫卓片的溶出度曲线。根据最终生产规模标准批次的批内和批间参数差异定义相似性区域（SR）。计算并归一化测试批次和参比批次参数均值之间的统计距离。围绕统计距离建立90%置信区域（CR）。将置信区域与相似性区域进行比较，以评估测试批次和参比（REF）批次溶出度曲线的相似性或不相似性。对两个测试批次进行了评估，一个有“微小”修改（mm），另一个有“重大”修改（MM）。