Reactions of Acetaminophen in Pharmaceutical Dosage Forms: Its Proposed Acetylation by Acetylsalicylic Acid

Abstract

Acetylation of acetaminophen (paracetamol) by acetylsalicylic acid to O,N-diacetyl-p-aminophenol (DAPAP) was not evident in experimental pharmaceutical dosage forms. DAPAP, which was found to be present in small quantities in commercial grade acetaminophen, is unstable in pharmaceutical preparations. The destruction of DAPAP increases rapidly with the temperature and moisture content of the system. Solid DAPAP seems to exist in at least two forms, as shown by their IR spectra. The observed color darkening of suspensions containing acetaminophen is mainly due to the oxidative degradation of the liberated p-aminophenol. The presence of codeine phosphate and caffeine seems to enhance the color deterioration of solid preparations containing acetaminophen kept at 45° and in a humid atmosphere. It is recommended that moisture be excluded, as much as possible, from such preparations.