Pharmaceutical grade paracetamol: Green chemistry approach to synthesis, analytical control and stability studies

The aim of this project was to assess the pharmaceutical quality of 5 batches of paracetamol synthesized according to green chemistry principles, in compliance with European Pharmacopoeia requirements. These batches were characterized by qualitative and quantitative analyses: chromatography, infrared spectroscopy and differential scanning calorimetry. The most compliant batches were subjected to stability tests and forced degradation tests. Analyses confirmed the identity of the paracetamol synthesized, with FTIR correlations > 98%. HPLC-DAD purities were as high as 77.3%, and the batches selected (2 and 4) met pharmacopoeial standards (assay: 99.6-100.8%; K impurities < 50 ppm; losses on drying < 0.5%). The forced degradation study showed increased sensitivity to oxidation and hydrolysis. The results of this work demonstrate the compliance of the paracetamol studied with European Pharmacopoeia standards, and underline the need for further long-term stability studies.