Abstract
The presence of impurities can drastically affect the efficacy and safety of pharmaceutical entities. p-Aminophenol (PAP) is one of the main impurities of paracetamol (PA) that can potentially show toxic effects such as maternal toxicity and nephrotoxicity. The removal of PAP from PA is challenging and difficult to achieve through regular crystallization approaches. In this regard, we report four new salts of PAP with salicylic acid (SA), oxalic acid (OX), l-tartaric acid (TA), and (1S)-(+)-10-camphorsulfonic acid (CSA). All the PAP salts were analyzed using single-crystal X-ray diffraction, powder X-ray diffraction, infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. The presence of minute amounts of PAP in paracetamol solids gives a dark color to the product that was difficult to remove through crystallization. In our study, we found that the addition of small quantities of the aforementioned acids helps to remove PAP from PA during the filtration and washings. This shows that salt formation could be used to efficiently remove challenging impurities.
Highlights
From a pharmaceutical point of view, unwanted substances existing in the final formulation are regarded as impurities or pollutants, and these impurities, even in minute quantities, sometimes compromise the stability and safety of the drug substance [1,2]
4-Aminophenol or p-aminophenol (PAP) is one of the major impurities in paracetamol (PA) and mesalazine (MZ), which originates from the synthesis and/or as a primary hydrolytic degradation product from storage conditions and that is difficult to remove [6,7]
The hydrophilic layers consist of the tartrate anions and the hydroxyl and ammonium groups of PAP, which all interact via H-bonding
Summary
From a pharmaceutical point of view, unwanted substances existing in the final formulation are regarded as impurities or pollutants, and these impurities, even in minute quantities, sometimes compromise the stability and safety of the drug substance [1,2]. Pharmaceutical companies dedicate their research in order to find new cost-effective methodologies to remove or avoid impurities from the final product [5]. Salts often show greater solubilities than the single individual components [6,28,29] Based on this knowledge, we prepared four organic salts of PAP in an attempt to efficiently remove knowledge, prepared this impuritywe from. Four organic salts of PAP in an attempt to efficiently remove this impurity fromRemoval. May be due to the cooling crystallization, to the best of the knowledge of the authors This may be due to the similar similar physical–chemical properties of the impurity with respect to the API.
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