Designing type V deep eutectic solvents with antimalarial pharmaceutical ingredients

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.

keywords

SOLID DISPERSIONS; SCREENING MODEL; COSMO-RS; DRUG; COCRYSTALS; DELIVERY; SYSTEMS; PYRIMETHAMINE; POLYMORPHS; SOLUBILITY

subject category

Pharmacology & Pharmacy

authors

Teixeira, G; Brandao, P; Ferreira, AIMCL; Abranches, DO; Santos, LMNBF; Ferreira, O; Coutinho, JAP

Groups

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, Portugal, UIDB/50011/2020, UIDP/50011/2020, and LA/P/0006/2020, CIQUP, Centro de Investigaca o em Quimica da Universidade do Porto, Portugal (UIDB/00081/2020) ; IMS, Institute of Molecular Sciences (LA/P/0056/2020) , and CIMO, Portugal, UIDB/00690/2020 (DOI: 10.54499/UIDB/00690/2020) and UIDP/00690/2020 (DOI: 10.54499/UIDP/00690/2020) ; and SusTEC, Portugal, 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, Portugal for his Ph.D. grant (UI/BD/151114/Supplementary data to this article can be found online at https://doi. org/10.1016/j.ejpb.2024.114463.