Formulation and Optimization of Nateglinide Loaded Polymeric Nanoparticles Using Response Surface Methodology”

摘要

The main purpose of proposed study was to identify and quantify ethylenediamine in morpholine and its impact on the quality of a pharmaceutical candidate. The drug substance impurity was determined to be a diamide dimer, resulting from a low level impurity (ethylenediamine) in one of the raw materials (morpholine). At the beginning ethylenediamine was not detected in morpholine using normal GC conditions however later ethylenediamine was detected and quantified at lower level by derivatizing with benzaldehyde. Morpholine was used as reagent as well as solvent throughout. As a result, it elucidated the formation of diamide impurity in the drug at higher level. Hence these studies describe the importance of understanding root causes of impurity formation to enable proper control strategies.