Abstract

Unused/expired pharmaceuticals can be regarded as a source of valuable compounds. Valorization of active pharmaceutical ingredients (APIs) from pharmaceutical waste, as an alternative to widely adopted treatment by incineration, is a big challenge in terms of designing green, efficient, scalable and sustainable separation methods. Concerning these demands, this work aimed to investigate and propose new integrated extraction technology based on aqueous biphasic systems (ABS) with eco-friendly components namely, poloxamer (Pluronic PE 6200) and one of two salts (sodium citrate, cholinium dihydrogenphosphate) or ionic liquid (1-butyl-3-methylimidazolium chloride). Liquid-liquid equilibria of each ABS were determined at room temperature followed by partition experiments in the biphasic medium to evaluate the most favorable systems for APIs extraction (acetaminophen and caffeine from one commercial product, and theophylline from the other). The finely designed ABSs were then employed to separate APIs from pharmaceutical solids and fractionate them. The results show that citrate-based ABS induces the strongest salting-out effect leading to extraction of all APIs to the Pluronic-rich phase with high recovery efficiencies between 79.4 and 97.90%; insoluble compounds were removed as residues while hydrophilic excipients remained in the citrate-rich aqueous phase. Ionic liquid/PL6200-based ABS was further applied to fractionate acetaminophen and caffeine toward opposite phases. These results underpin the viability and adjustability of PL6200-based ABSs within an integrated process, by a deftly selected salting-out agent, as a sustainable and efficient alternative platform with the great potential to be implemented on a larger scale.

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