Quality by design-guided development of a capillary electrophoresis method for the chiral purity determination of silodosin.

ABSTRACT

Silodosin is a single isomer selective α1-adrenoreceptor antagonist used for the treatment of benign prostatic hyperplasia. In order to control the enantiomeric purity of the drug a capillary electrophoresis method was developed that is applicable to the analysis of drug substance as well as pharmaceutical formulations. Method development followed a quality by design strategy. After selection of carboxymethyl-ß-cyclodextrin as suitable chiral selector and the starting conditions in the scouting phase, a two-level full factorial design was applied to identify the critical process parameters. The final method optimization was performed using a face-centered central composite design resulting in the conditions 100 mM sodium phosphate buffer, pH 2.9, containing 40 mg/mL car-boxymethyl-ß-cyclodextrin, a capillary temperature of 17 °C and an applied voltage of 28 kV. Robustness testing employing a Plackett-Burman design revealed the importance of careful pH adjustment in order to achieve suitable peak shape and resolution. The method was validated according to the guideline Q2(R1) of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use and applied to the analysis of a commercial capsule formulation.