Solubility and Stability of Carvedilol in Deep Eutectic Solvents: A Step Towards a Sustainable Pharmaceutical Formulation in the Liquid State

Abstract

Carvedilol is used to treat chronic hypertension, chronic stable angina pectoris and concomitant treatment heart failure and class II of the Biopharmaceutics Classification System (low solubility and poor bioavailability). This drug is only formulated as tablets, and liquid oral formulations are not available on the market. In this work, several aqueous eutectic mixtures formed by xylitol, citric acid, sorbitol and glucose (HBD) and choline chloride as HBA have been used to improve the solubility. Additionally, SwissADME was used to obtain physicochemical and pharmacokinetic parameters to further knowledge on the ADME (absorption, distribution, metabolism and excretion) parameters for carvedilol.The results reveal that the solubility of carvedilol increases as the content of water decreases, and the mixture formed by citric acid and choline chloride (CACh10) was the most soluble. The stability study shows that carvedilol in DES is stable during the test time, as the maximum and minimum concentration losses were 19.0 % and 0.2 %, respectively. These results help advance the green and sustainable development of new medicines in the liquid state.