abstract
Hydrotropy is a well-established strategy to enhance the aqueous solubility of hydrophobic drugs, facilitating their formulation for oral and dermal delivery. However, most hydrotropes studied so far possess toxicity issues and are inefficient, with large amounts being needed to achieve significant solubility increases. Inspired by recent developments in the understanding of the mechanism of hydrotropy that reveal ionic liquids as powerful hydrotropes, in the present work the use of cholinium vanillate, cholinium gallate, and cholinium salicylate to enhance the aqueous solubility of two model drugs, ibuprofen and naproxen, is investigated. It is shown that cholinium vanillate and cholinium gallate are able to increase the solubility of ibuprofen up to 500-fold, while all three ionic liquids revealed solubility enhancements up to 600-fold in the case of naproxen. Remarkably, cholinium salicylate increases the solubility of ibuprofen up to 6000-fold. The results obtained reveal the exceptional hydrotropic ability of cholinium-based ionic liquids to increase the solubility of hydrophobic drugs, even at diluted concentrations (below 1 mol.kg(-1)), when compared with conventional hydrotropes. These results are especially relevant in the field of drug formulation due to the bio-based nature of these ionic liquids and their low toxicity profiles. Finally, the solubility mechanism in these novel hydrotropes is shown to depend on synergism between both amphiphilic ions.
keywords
BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; AQUEOUS-SOLUTIONS; IMPROVE SOLUBILITY; NICOTINAMIDE; DISSOLUTION; WATER; ENHANCEMENT; ACID; CYCLODEXTRINS; COMPLEXATION
subject category
Pharmacology & Pharmacy
authors
Sintra, TE; Abranches, DO; Benfica, J; Soares, BP; Ventura, SPM; Coutinho, JAP
our authors
Dinis O. Abranches
Assistant Researcher
Jordana Benfica
Collaborator
Sónia Patrícia Marques Ventura
Assistant Professor
Tânia Ereira Sintra
Post-Doc FellowshipGroups
G4 - Renewable Materials and Circular Economy
G6 - Virtual Materials and Artificial Intelligence
Projects
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
acknowledgements
This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the Portuguese Foundation for Science and Technology/MCTES. The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project N. 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). J.B.S. acknowledges FCT for her Ph.D. grant 2020.05802.BD. B.P.S. acknowledges FCT for her Ph.D. grant SFRH/BD/138439/2018.