abstract
This work studies the formation of deep eutectic solvents formed by one active pharmaceutical ingredient (quinine, pyrimethamine, or 2-phenylimidazopyridine) and a second component potentially acting as an excipient (betaine, choline chloride, tetramethylammonium chloride, thymol, menthol, gallic acid, vanillin, acetovanillone, 4-hydroxybenzaldehyde, syringaldehyde, propyl gallate, propylparaben, or butylated hydroxyanisole), aiming to address challenges regarding drug solubility, bioavailability, and permeability. A preliminary screening was carried out using the thermodynamic model COSMO-RS, narrowing down the search to three promising excipients (thymol, propyl gallate, and butylated hydroxyanisole). Nine solid–liquid equilibrium (SLE) phase diagrams were experimentally measured combining the three model drugs with the screened excipients, and using a combination of a visual melting method and differential scanning calorimetry. Negative deviations from thermodynamic ideality were observed in all nine systems. Furthermore, a total of four new cocrystals were found, with powder and single crystal X-ray diffraction techniques being employed to verify their unique diffraction patterns. In the thermodynamic modelling of the SLE diagrams, two COSMO-RS parametrizations (TZVP and TZVPD-FINE) were also applied, though neither consistently delivered a better description over the other.
authors
Teixeira, G; Brandão, P; Lobo Ferreira, AIMC; Abranches, DO; Santos, LMNBF; Ferreira, O; Coutinho, JAP
our authors
Dinis O. Abranches
Assistant Researcher
Gabriel Teixeira Santos
PhD Student
Paula Cristina Ferreira da Silva Brandão
Assistant ResearcherGroups
G1 - Porous Materials and Nanosystems
G4 - Renewable Materials and Circular Economy
G6 - Virtual Materials and Artificial Intelligence
Projects
Collaboratory for Emerging Technologies, CoLab (EMERGING TECHNOLOGIES)
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
acknowledgements
This work was developed within the scope of the project CICECO - Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020, and LA/P/0006/2020, CIQUP, Centro de Investigação em Química da Universidade do Porto (UIDB/00081/ 2020); IMS, Institute of Molecular Sciences (LA/P/0056/2020), and CIMO, UIDB/00690/2020 (DOI: 10.54499/UIDB/00690/2020) and UIDP/00690/2020 (DOI: 10.54499/UIDP/00690/2020); and SusTEC, LA/P/0007/2020 (DOI: 10.54499/LA/P/0007/2020), financed by national funds through the Portuguese Foundation for Science and Technology FCT/MCTES (PIDDAC). AIMCLF is financed by national funds through the FCT-I.P., in the framework of the execution of the program contract provided in paragraphs 4, 5, and 6 of art. 23 of Law no. 57/2016 of 29 August, as amended by Law no. 57/2017 of 19 July. G.T. thanks FCT for his Ph.D. grant (UI/BD/151114/2021).