Sampling Bias in Blending Validation and a Different Approach to Homogeneity Assessment

Abstract

Sampling of batches studied for validation is reported. A thief particularly suited for granules, rather than cohesive powders, was used in the study. It is shown, as has been demonstrated in the past, that traditional 1× to 3× thief sampling of a blend is biased, and that the bias decreases as the sample size increases. It is shown that taking 50 samples of tablets after blending and testing this subpopulation for normality is a discriminating manner of testing for homogeneity. As a criterion, it is better than sampling at mixer or drum stage would be even if an unbiased sampling device were available.

Key Words:

• Blending
• Normal distribution
• Sampling
• Sampling bias
• Thief