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. Keywords: bisoprolol film-coated tablet, dissolution profiles, model-independent multivariate statistical distance, model-dependent multivariate statistical distance