Implementation of Quality by Design Methodology in Development and Validation of a New Stability-Indicating, Reverse Phase High-Performance Liquid Chromatography Method for the Rapid Estimation of Piribedil in Piribedil Prolonged Release Tablets

Abstract

Kumar et al.: Quality by Design based Reverse Phase High-Performance Liquid Chromatography Method for Assay of Piribedil in Tablets Piribedil is a diazinane compound used in the treatment of Parkinson's disease. The objective of the current work was to develop a Quality by design based, stability-indicating high-performance liquid chromatography method, with a short runtime to estimate assay in piribedil prolonged release tablets.The assay is an important critical quality attribute of the drug product, which ensures its efficacy. The critical quality attributes were identified and the quality target method profile was defined. Basis of the initial risk assessment, the separation between piribedil and known/unknown degradation products and the sample preparation procedure's robustness were considered critical factors. Phosphate buffer with 0.01 % triethylamine (pH 2.5; 50 mM) and acetonitrile (80:20, v/v) were used as mobile phase. The peaks were resolved using Hypersil gold C18, (4.6×150) mm, 5 µm column within a runtime of 5 min. The mobile phase was pumped at a flow rate of 1.3 ml/min, whereas the column was maintained at 30°. A 5 µl aliquot of each solution was injected and the peak responses were recorded at 238 nm. The critical chromatographic parameters and sample preparation steps were optimized by using Design of experiments and based on its outcome, method operable design ranges were demarcated. An extensive forced degradation study was executed and all the degradant peaks were well separated from the piribedil peak. Piribedil peak was also found homogenous in all the stressed samples. The developed method was validated and found specific, precise, linear, accurate, rugged and robust.