Deep eutectic solvents based on sugars for oral applications (versión aceptada)

Abstract

Solubility is a critical parameter in drug formulation to achieve the desired therapeutical concentration. Most drugs are weak acids or bases and, therefore, exhibit low solubility and poor oral availability. The main aim of this work is the use of Deep Eutectic Systems (DESs) for improving the solubility of drugs in aqueous medium. In this case, we use DESs formed by choline chloride and sugars (xylitol, fructose, glucose and sorbitol) at different proportions of water. These compounds present low toxicity, and thus can be used in syrups or liquid formulations. Different physicochemical properties, such as density, refractive index, and surface tension, were obtained. In addition, a rheological study of the different systems was carried out. Finally, these DESs were applied to analyse the solubility of the following active principles: caffeine (Class I) and furosemide (Class IV) of the Biopharmaceutics Classification System (BCS). The selection of the drugs attends to different reasons. On one hand, we want to develop a new liquid formulation for model drug furosemide and, on the other hand, the study of caffeine, instead, will be used as a model for comparing purposes. Solubility results show that the systems that best solubilize caffeine are those with the highest water content; however, they do not reach the levels of solubility of pure water. On the other hand, for furosemide, a great increase in solubility was observed, especially for systems formed by xylitol and, fundamentally, in the system with the lowest water content. Obtaining an increase in solubility of up to 4530 times. These systems provide an opportunity to improve the formulation of drugs in the liquid medium of active ingredients that are poorly soluble in an aqueous medium.