Quality-by-design driven analytical method (AQbD) development and validation of HPLC–UV technique to quantify rivastigmine hydrogen tartrate in lipidic nanocarriers: Forced degradation, and assessment of drug content and in vitro release studies

Abstract

The main purpose of current investigation was to design and further validate a technique for the quantitative determination of rivastigmine hydrogen tartrate (RHT), a cholinesterase inhibitor in the nano formulations. With the employment of a reverse phase C18 column and a very simple mobile phase, an isocratic HPLC–UV analysis technique was developed, optimized, and validated following ICH Q2 (R1) requirements along with the inculcation ofAnalytical Quality-by-Design (AQbD) methodology. A two-level full factorial screening design was applied to filter out the variables influencing responses, followed by the application of central composite design (CCD) to further optimize the method using Design-Expert® software. Analyses were performed at room temperature with 0.9 mL. min−1 flow rate and detection wavelength of 215 nm. The optimized HPLC technique exhibited superior linearity, selectivity, and precision. The inherent stability of RHT was evaluated using the optimized method byconductingforced degradation studies. The RHT peak was clear and unaffected by matrix interference in the specimens from the forced degradation studies, drug content analysis, and in vitro release study. The assay had a limit of detection (LOD) of 14.32 ng. mL−1 and a limit of quantitation (LOQ) of 43.40 ng. mL−1. With acceptable intra- and interday precision, the methodologywas confirmedto berobust. The devised stability-indicating HPLC technique for analyzing RHT content, its stability in the nano formulations, and drug release in vitro proved to be selective, accurate, sensitive, and consistent.