Forced Degradation Study of Budesonide Drug Substance and Nebulizer Suspension Using HPLC and LC-MS

Abstract

“Budesonide is a novel drug that is used in the treatment of breathing difficulty, chest tightness, wheezing and coughing due to asthma. In the present work, stability indicating method of budesonide was developed and validated in the presence of process related impurities and degradation products using HPLC. The chromatographic separation was achieved on Waters Spherisorb ODS2 C18 (150×4.6mm,3.0μm) at 50°C. The peaks of Budesonide and its known impurities were separated using Ethanol: Buffer: Acetonitrile (2:66:34, %V/V/V) as mobile phase A and Buffer: Acetonitrile (66:34, % V/V) as mobile phase B in gradient program. The analytes were monitored in the range 200-400 nm using photo diode array (PDA) detector. The method was validated as per ICH Q2 (R1) guideline and all the validation parameters were found to be in the range of acceptance criteria. The forced degradation study of budesonide showed that the drug is susceptible to degrade in alkaline and photolytic condition. To identify the major degradation products MS compatible method was developed using Water: 0.1% Formic Acid: Ethanol (34:64:2, %V/V/V) as mobile phase. The LC-MS study revealed 5 different degradation products, out of which two were known impurities and three were unknown degradation products. The probable degradation pathway is illustrated in the thesis.