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-PURPOSE. Pyrimethamine, an anti-malarial agent known to exhibit solid state polymorphism, may be purified by means of recrystallization. Recrystallization may alter the solid state chemistry of pharmaceuticals, which may impact the toxicity and/or manufacturability thereof. We evaluated the risks associated with the recrystallization of pyrimethamine. METHODS. Pyrimethamine was recrystallized using several organic solvents. X-ray diffraction, thermal analysis, infra-red spectroscopy, microscopy, flowability -, solubility and dissolution testing as well as computational work were employed to evaluate the recrystallized products. RESULTS. A toxic solvatomorph of pyrimethamine (Pyr-MeOH) was found to be the product from methanol recrystallization. The elucidation of -and the elaboration on the unique characteristics of Pyr-MeOH provides the pharmaceutical industry with several means to identify Pyr-MeOH and to distinguish it from the pharmaceutically preferred anhydrous form (Pyr). Thermal methods of analysis found that the toxicity of PyrMeOH may be reversed by overcoming a desolvation activation energy of 148 kJ/mol. In addition it was found that recrystallization altered the morphology of Pyr. Angle of repose and tapped density determinations identified that the different morphologies of Pyr displayed differences in powder flow and compressibility behaviour and In Silico calculations were successful in rendering morphologies resembling that found experimentally. CONCLUSION. We present a solvatomorph of pyrimethamine and provide several characteristic means to identify this unwanted toxic form and quantified the energy required to overcome its toxicity. In addition we describe that Pyr may present in different morphologies and show how it may impact the manufacturability thereof.

A Pharmaceutical Quality Control Laboratory (PQCL) is one of the critical pillars in the quality assurance of medicines to ensure the availability of safe and efficacious medicines. It is thus of critical importance that the PQCL should be able to continue delivering its service to the greater public. With the reporting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 as the causative agent of COVID-19, a new health and safety threat was introduced into greater society and specifically the workplace. The aim of this manuscript is to provide practical guidance and easy access reference to information sources for PQCL managers in an attempt to ensure safer working environments for the analytical and administrative staff of PQCLs, and to support the continued availability of quality assured medicines world-wide during this pandemic.