Raman imaging studies on the stability of Paracetamol tablets under different storage conditions

The applicability of Raman imaging for pharmaceutics production ranges from the characterization of pharmaceutical formulations, kinetic processes in drug delivery to the rapid detection and identification of counterfeit drugs/contaminants. Acetaminophen (Paracetamol, APAP) is an analgesic and antipyretic drug and one of the most consumed medicines worldwide. On the other hand, the compound 4-aminophenol (4-AP) is a hydrolytic product of APAP with nephrotoxicity and teratogenic effects. In this work, we have explored for the first time Raman imaging methods to characterize the main components of commercial APAP tablets (APAP-tablets) and to inquire about the potential of this optical technique to identify 4-AP in APAP tablets, which have been previously spiked with such contaminant. The laboratorial treated APAP-tablet samples were subjected to different temperature, humidity and sunlight exposure conditions, mimicking storage conditions, and then the Raman spectra and images were collected to monitor changes that might occur in those conditions. Although the lower limit of detection of 4-AP in APAP-tablets is above the minimum levels established by Pharmacopoeias (0.005 %), this research demonstrates that Raman imaging still allows the detection of small amounts of the contaminant, thus opening perspectives for exploring this technique for characterizing APAP products.