Determination of mometasone furoate solubility, using deep eutectic systems, and topical formulation- experimental and computational studies

Abstract

The low solubility of some drugs in aqueous medium, is currently a challenge for the pharmaceutical industry, affecting drug bioavailability and treatment efficacy, so there is the need to find new solutions for this challenge. In this work, the solubility of a glucocorticoid drug, mometasone furoate (MF), in different deep eutectic systems (DES) is studied. DES present the advantage of being sustainable solvents, which can be used directly in the final formulation, and establish a synergistic effect with the drug. The solubility of MF in different DES is increased, when compared to the solubility of this drug in an aqueous medium, particularly in DES composed by levulinic acid and terpenes such as menthol and thymol, where the solubility of MF was of 24.1 and 103.3 mgMF/gDES, respectively. Solubility was also assessed using the computational determination of the Hansen solubility parameters of MF in these DES, in particular the total solubility parameter (δT) and Relative Energy Difference (RED). The obtained results correlate well with the MF measured experimentally, showing that this computational tool can be further used to predict MF solubility in DES. Furthermore, oil-in-water emulsions containing DES with MF were developed, allowing more versatility compared to the drug in powdered form, and were prepared containing 1 and 5 % of DES with MF. This work highlights that DES can have an important role in drug solubilization and in the development of new formulation strategies for the pharmaceutical industries.