Abstract

MICROWAVE ASSISTED COMPARATIVE FORCED DEGRADATION STUDY OF ORAL CEPHALOSPORIN DRUGS USING QUALITY BY DESIGN (QbD) APPROACH AND STABILITY INDICATING RP-HPLC ANALYSIS

Dilip K. Prajapati*, Jayant B. Dave, Chhagan N. Patel

ABSTRACT

The objective was to perform comparative stability study among different oral Cephalosporins based on microwave assisted degradation using QbD Approach. Optimization of parameters like power (temperature), stressor (acid/alkali strength) and time was done to generate multivariate factorial design for achieving sufficient degradation in the range of 10-20 % in acidic and alkaline conditions. Separate RPHPLC methods for analysis of Cefixime, Cefpodoxime and Cefadroxil in presence of respective degradation (stress) samples were optimized by making suitable modification of Pharmacopoeial/published method. Three independent critical attributes like microwave power, stressor & irradiation time were selected as input parameters and percentage degradation selected as output parameter for the purpose of microwave - assisted degradation using Box-Behnken Design. The methods showed good precision & linearity from 40-140 μg/mL for all the drugs. Each method was capable of separating the Cephalosporin drug from its degradation products with good peak purity index and resolution signifying specificity. Cefixime & Cefadroxil were found to be more susceptible to alkaline hydrolysis as compared to acidic hydrolysis whereas Cefpodoxime is highly susceptible to both acidic and alkaline hydrolysis. The Box- Behnken application showed goodness of fit. The significance of the model was judged on the basis on ANOVA for Response Surface 2FI model with observed. p value being ≤0.05. Design space region showed more dependency on power indicative of temperature as compared to stressor indicative of acid or alkaline strength and time.

Keywords: QbD, Experimental design, Comparative degradation of Cephalosporins, Microwave assisted degradation, HPLC assay.