Optimization of Robust HPLC Method for Quantitation of Ambroxol Hydrochloride and Roxithromycin Using a DoE Approach

Abstract

The aim of this work was to develop and optimize a robust HPLC method for the separation and quantitation of ambroxol hydrochloride and roxithromycin utilizing Design of Experiment (DoE) approach. The Plackett-Burman design was used to assess the impact of independent variables (concentration of organic phase, mobile phase pH, flow rate and column temperature) on peak resolution, USP tailing and number of plates. A central composite design was utilized to evaluate the main, interaction, and quadratic effects of independent variables on the selected dependent variables. The optimized HPLC method was validated based on ICH Q2R1 guideline and was used to separate and quantify ambroxol hydrochloride and roxithromycin in tablet formulations. The findings showed that DoE approach could be effectively applied to optimize a robust HPLC method for quantification of ambroxol hydrochloride and roxithromycin in tablet formulations. Statistical comparison between results of proposed and reported HPLC method revealed no significant difference; indicating the ability of proposed HPLC method for analysis of ambroxol hydrochloride and roxithromycin in pharmaceutical formulations.

Design, development and optimization of new high performance thin‐layer chromatography method for quantitation of Retapamulin in pharmaceutical formulation: Application of design of experiment

“…Linearity was predicted by estimating the regression coefficient (R 2 ), and the linear regression y‐intercept of the response versus concentration plot. Additionally, the residual plots for the sets of test data was generated .…”

“…System suitability test was carried out by analyzing the quality attributes in the data from the optimized HPTLC method, from six replicate injections of freshly prepared standard solution (100% concentration of analyte). The quality attributes monitored included R f value, injection precision, tailing factors, efficiency and peak purity of the analyte peaks .…”

“…Considering this fact, the International Council for Harmonisation of technical requirements for pharmaceuticals for human use (ICH) and Food and Drug Administration (FDA) have recently demanded systematic approach in development of analytical method using Design of Experiment (DoE) to ensure robust analytical method performance. DoE helps to understand the quantitative effect of individual factor as well as inter‐relationship between factors and screen a large number of factors to identify important ones to develop robust analytical method .…”

Design of Experiment Centered Multivariate Optimization Strategy for RP-HPLC Method to Quantitate Retapamulin in Topical Cream and Microemulsion

“…The selected chromatographic (independent) factors and implementation of PBD for their screening purpose are as shown in Tables 1 and 2, respectivley. 17,18 Optimization of RP-HPLC method using Box Behnken design DoE concept was applied to study and understand the influence of a multivariate approach in the optimization of the RP-HPLC chromatographic factors. 11 For the optimization of the RP-HPLC method based on the DoE approach, response surface design is the best choice.…”

Analysis of organophosphate pesticides in surface water—Comparison of method optimization approaches

“…DOE allows the deduction of valid results after conducting a number of systematic experiments. 27 These statistical tools have been used to support method optimization for many chemical fields such as removal of organic pollutants, 28 liquid-liquid micro-extraction of polycyclic aromatic hydrocarbons, 29 removal of OPP from aqueous solutions, 30 or optimization of high-pressure liquid chromatography (HPLC) methods, 31 to name only a few. DOE tools reveal a maximum of useful information with the smallest required number of systematic experiments.…”