QbD-Based Development and Validation of Novel Stability-Indicating Method for the Assay and Dissolution of Garenoxacin in Garenoxacin Tablets

Abstract

Background Garenoxacin mesylate is a novel des-fluoro (6) quinolone, approved and marketed for human use in Japan under the name Geninax. Objective In this current work simple and stability indicating methods for the assay and dissolution of Garenoxacin in Garenoxacin tablets 200 mg was performed. Method developed for the particle size measurement of Garenoxacin mesylate API using Malvern 2000. Methods QbD based Stability indicating assay method was developed using 0.1% v/v formic acid in water and methanol (70:30). Using PDA detector the peak purity of Garenoxacin peak for all degradation samples was studied. BCS solubility of Garenoxacin mesylate API was studied by modified shake flask method. Dissolution test method was developed using 0.1 N Hydrochloric acid as medium, USP apparatus-II, rpm -50, temperature 37 ± 0.5 °C and time 30 min. Liquid paraffin was used as the dispersant in the particle size measurement of Garenoxacin mesylate API using, Malvern Mastersizer—wet method. Results QbD based RP-HPLC method was stability indicating, simple, precise and accurate. Assay method was linear over 12.5 to 75 µg/mL at the detection wavelength of 280 nm. UV based method was developed and validated for the dissolution of Garenoxacin 200 mg tablets, method was found to be linear over 2.9 to 34.2 µg/mL at 280 nm. Based on data, Dissolution Tolerance for Garenoxacin 200 mg tablets was proposed as Q not less than 80% at time 30 min. Effect of Garenoxacin mesylate API particle size in the tablet dosage form was studied using particles of 92 µm and 220 µm (D90) and found that there is no impact on the in-vitro dissolution profile. Conclusion Reported stability indicating assay and dissolution test methods can be used in the regular QC testing of Garenoxacin 200 mg tablets. Malvern Particle size wet dispersion measurement method developed and validated for Garenoxacin mesylate API is simple and robust. Highlights QbD based RP-HPLC method (using Design Expert Software version 11) and studied peak purity of Garenoxacin peak using photo diode array detector (for all degradation samples, control sample and standard solution) and the same method is validated following USP and ICH guidelines. LC-MS compatible volatile buffer solution is used in the mobile phase preparation of the novel Stability indicating RP-HPLC assay method.