Optimization and statistical evaluation of discriminative dissolution method for bisoprolol immediate-release film coated tablets

This study presents optimization of a statistically based approach for setting up the
dissolution test conditions for bisoprolol film-coated tablets using multivariate release models
as predictive in vivo assessment tools for formulation behaviour. Additionally, the dissolution
profiles of three different strengths of bisoprolol film-coated tablets were evaluated. According
to the biopharmaceutics classification system, the tested medicinal product belongs to BCS
Class I (high solubility, high permeability).
Three dissolution media, including the dissolution medium of choice (pH 1.2)
according to the USP monograph for bisoprolol tablets and two apparatus, paddle and basket
were applied. The optimal conditions for performing the dissolution test were following: 900
mL of pH 1.2 as dissolution medium, apparatus 2 (paddle) with 75 r/min stirring speed. The
quantity of the released active substance was determined using HPLC method.
For a reliable statistical analysis, multivariate methods such as model-dependent
approach coupled to multivariate statistics (Weibull), multivariate model-independent
approach based on generalized statistical distance (Mahalanobis distance) have been applied
for evaluation of dissolution profiles. All applied statistical approaches unequivocally support
the underlying similarity of the pairs in different media between different strengths. Moreover,
the optimized dissolution method has a discriminatory power to reflect the characteristics of
the medicinal product in order to distinguish any changes related to quantitative composition
of the formulation.