Thermal behavior of a pharmaceutical solid acetaminophen doped with p-aminophenol

Thermal behavior of a series of acetaminophen (APAP) doped with p-aminophenol (PANP) was studied by differential scanning calorimetry (DSC) to determine whether it exhibited a eutectic system. Within the temperature range of 120 to 200 degrees C, accurately weighed (1-2 mg) samples sealed in hermetic pans were calorimetrically scanned with a low scanning rate of 1 degrees C/min. The mixture formed a single eutectic with the composition ratio APAP/PANP of 0.6/0.4 at a temperature of 138 degrees C, where it liquefied. Melting began as early as at the eutectic point, which was below the melting temperature of APAP (169 degrees C). The melting point as well as heat of APAP fusion was depressed with the increase in doped PANP. It was postulated that there might be a deficit heat of APAP fusion in APAP doped with PANP, which was coincident with the heat consumed by early liquefaction. The deficit heat was used to correct fraction molten in the van't Hoff law of purity determination. It was found that the purity determination of APAP doped with PANP was comparable to the UV-spectroscopic method up to the maximum doped PANP level of 8 mol percent. It was concluded that DSC was able to approach early heat of liquefaction of APAP doped with PANP. The van't Hoff law may be applicable to the determination of APAP with the presence of PANP as a eutectic impurity.