Solubility of acetaminophen in aqueous solutions of three natural deep eutectic solvents (NADESs) and individual components of the NADESs

Abstract

Acetaminophen is a poorly water-soluble drug whose solubility in water can be increased by adding cosolvents. Using non-toxic or low toxic cosolvents is of interest in the pharmaceutical industry. In this work, the effect of three natural deep eutectic solvents (NADESs), choline chloride + l-malic acid, choline chloride + malonic acid, and choline chloride + urea, was experimentally studied on the aqueous solubility of acetaminophen in the temperature range of 293.15 K to 323.15 K. Besides the NADESs, the individual components of the NADESs were also examined to increase the aqueous solubility of acetaminophen. The results showed that the solubility of acetaminophen increased with an increase in the temperature or an increase in the concentration of the studied cosolvents. The most effective and least effective cosolvents were choline chloride and urea, respectively. For instance, an aqueous solution of 6.45% choline chloride by mole increased the solubility of acetaminophen to more than 4 times the solubility in deionized water. The solubility of acetaminophen in the aqueous solutions of the individual components of the NADESs was used for estimating the binary interaction parameters of the NRTL for these systems. The AARD of the model was obtained to be 3.2% for calculating the solubility of acetaminophen in the aqueous solutions of the individual components of the NADESs. Then, the binary interaction parameters were employed to predict the solubility of acetaminophen in the aqueous NADESs. The AARD of the model was obtained to be 6.2% for predicting the solubility of acetaminophen in the aqueous NADESs which indicate the reliable predictability of the model.