Application of linear mixed effects models to the evaluation of dissolution profiles

The performance of linear mixed effects models for the comparison of dissol ution profiles is examined. This type of model is frequently used by statis ticians, but is rather unknown to people that work in dissolution laborator ies. Hence, an extensive theoretical part was introduced to make the method ology more accessible. Firstly, repeated measures ANOVA is discussed, follo wed by the 'real' linear mixed effects models. The theory is applied to two types of dissolution data: one corresponding to an immediate and another t o a slow release formulation. We tried to use as much as possible the stand ard settings of the statistical software (S-plus). Suggestions are given to solve problems encountered during model fitting. It was found that the sta tistical limits are much more discriminative than the similarity factor. (C ) 2001 Elsevier Science B.V. All rights reserved.