Deep eutectic systems as enabling pharmaceutical formulations. mechanisms and applications

Abstract

New pharmaceutical chemical entities discovered in research often fail in development, due to poor biopharmaceutical performance, especially regarding aqueous solubility. Deep eutectic solvents or related systems (DES) are a new type of liquid with promising applications in solubility-enhancing pharmaceutics. DES are distinguished from the umbrella term eutectic solvents because their eutectic temperature is clearly lower than that of an ideal binary system from a thermodynamic viewpoint. DESs have been extensively studied and applied in the fields of green chemistry and chemical engineering, mainly for extraction purposes. Over the last decade, several studies have reported that DESs are excellent solubilizers of poorly soluble compounds, making them viable candidates for solubility-enabling formulations. This review aims to provide a thorough introduction to DESs and their material properties in comparison to other similar multicomponent systems, while also providing an overview of eutectic, DES, and therapeutic DES (THEDES) systems from the perspective of their potential application as enabling formulations. Additionally, an overview of computational studies on DESs is provided, where the techniques used to mechanistically study DES properties, including solubility and toxicity, are listed. The review concludes that DES liquids can be utilized as enabling formulations and that increased oral bioavailability would not only be beneficial from a biopharmaceutical perspective but also help reduce the amount of environmentally harmful active pharmaceutical ingredients (APIs). This increased bioavailability offers a further sustainability advantage, making this formulation strategy particularly attractive.