Development of Green High Performance Liquid Chromatography Method for Determination for Ranitidine Hydrochloride in Solid Dosage Form by Applying Lean Sigma principles

This study was applied in developing new reverse phase liquid chromatographic method to reduce the organic solvent from the analytical method by applying the Lean Six Sigma (LSS) methodology and waste management. LLS is considered one of the successful approaches in the field of quality improvement and cost reduction. A simple, specific and accurate reverse phase liquid chromatographic method has been developed for the estimation of Ranitidine HCl from tablet formulation. The drug is official with Indian Pharmacopeia, United States Pharmacopeia British Pharmacopoeia, however these Compendial procedures does not involve aqueous solvent as diluents. Define, Measure, Analysis, Improve and Control (DMAIC) principles were used for problem solving, root cause investigation, risk management to improve method performance. The process capability evaluation of the method before and after modification revealed that proposed method has better process capability. We subjected a high performance liquid chromatographic (HPLC) analytical procedure used for quantification of Ranitidine HCl to a Failure Mode and Effects Analysis (FMEA), including technical risks as well as risks related to human failure. An FMEA tool broke down the HPLC analytical method into process steps and identified possible failure modes for each step. Each failure mode was ranked on estimated frequency of occurrence (O), probability that the failure would remain undetected later in the process (D) and severity (S), each on a scale of 1-10. Failure risks were calculated by Risk Priority Numbers (RPNs) = OxDxS. Failure modes with the highest RPN scores were subjected to corrective actions and the FMEA was repeated, showing reductions in RPN scores and resulting in improvement indices up to 5.0. The separation was carried out using 25 cm x 4.0 mm packed with octadecylsilane bonded to porous silica (10 mu m) column and the mobile phase consisted of (methanol: ammonium Acetate-85: 15) in isocratic mode. The flow rate was 1.00 ml/min and effluent was monitored at 322 nm. The method was successfully used for quantitative determination of Ranitidine HCl from tablet dosage form. The capabilities of IP and new assay methods were determined and compared. It was studied which factors had the largest effects on the capability of chromatographic HPLC methods in order to reduce the organic solvent and improve their precision and accuracy. This was done using DMAIC principles. The investigations showed that it was feasible to define an alternative HPLC method with a better capability as the IP method. Aqueous solution of Ranitidine HCl tablet formulation was found with enhanced the method capability with solution stability up to 72h.