New insights on the thermal behavior of acetaminophen

Abstract

Acetaminophen is one of the most extensively marketed analgesic and antipyretic of the nonsteroidal anti-inflammatory drug class. A deep study concerning acetaminophen by TG/DTG/DTA, DSC, P-DSC, FTIR, PXRD, TG-FTIR and Kinetic study is presented in order to review its thermal behavior and to explore new insights and better understand some details. When heated under room pressure, the polymorphic Form I (monoclinic) of the pharmaceutical underwent a mixture of evaporation and decomposition just after melting at 168.5 °C. However, if cooled down at 10 °C min−1, a partial crystallization of Form III at 93.3 °C was observed. Such form completed crystallization on new heating 78.7 °C, followed by a solid transformation to Form II (orthorhombic) at 133.1 ºC, as confirmed by PXRD data, and it is melting at 158.8 °C. P-DSC experiments revealed that under sub-ambient pressure, the drug preferentially evaporates after melting, and if pressure is risen above the room, a mix of evaporation and decomposition tended to a preferential decomposition. The analysis of evolved gases demonstrated the release of ammonia, methane, carbon monoxide and phenol. The further detection of 4-aminophenol suggested that the decomposition can occurs toward a dimeric form of the drug via interaction between the amide groups. Kinetic study based on a non-isothermic model-free method was used to determine the kinetic triplet values (Eα, LogAα, and n) for parallel evaporation process and the degradation with releasing of gases on heating, which resulted in a unique step of mass loss. Based on all of these results, a mechanism for thermal behavior of acetaminophen has been proposed.