Characterizing the Solvation Characteristics of Deep Eutectic Solvents Composed of Active Pharmaceutical Ingredients as a Hydrogen Bond Donor and/or Acceptor
Muhammad Qamar Farooq, Nabeel Mujtaba Abbasi, Emily A. Smith, Jacob W. Petrich, Jared L. Anderson
Abstract
The formation of eutectic mixtures from active pharmaceutical ingredients (APIs) has emerged as an effective technique to develop liquid pharmaceutical formulations. API-based deep eutectic solvents (DESs) enhance the water solubility of APIs and avoid their recrystallization. The physicochemical properties of API DESs can be easily modulated by judicious selection of a hydrogen-bond acceptor (HBA) or hydrogen-bond donor (HBD) excipient that is mixed with the API. Solvation properties of API DESs can help in understanding the role of ionic and nonionic excipients toward the overall solvation interactions of these DESs. In this study, the solvation characteristics of three subclasses of API DESs containing API HBAs, API HBDs, or API HBAs and API HBDs are investigated. Inverse gas chromatography is employed to study solute–solvent interactions of a variety of probe molecules for 20 different API DESs. Among the API DESs composed of API HBAs and carboxylic acid- or diol-based HBDs, DESs containing diol-based HBDs exhibited stronger dipolar, hydrogen-bond basicity, and hydrogen-bond acidity interactions compared to carboxylic acid-based HBDs. No significant differences were observed in the solvation properties of DESs composed of API HBAs and API HBDs. API DESs composed of the choline chloride HBA and API HBDs exhibited stronger hydrogen-bond acidity and dipolarity and weaker dispersive-type interactions among the DESs evaluated in this study. An in-depth evaluation of solvation properties for these DESs is important to completely exploit their potential in separation science as well as the fields of biomaterial science, pharmaceutical chemistry, and biotechnology.