CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
Eur J Pharm Biopharm. 2021 Jul;164:86-92. doi: 10.1016/j.ejpb.2021.04.013. Epub 2021 Apr 23.
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), 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.
水增溶是一种提高疏水性药物水溶性的成熟策略，有助于将其制成口服和皮肤给药制剂。然而，迄今为止研究的大多数水增溶剂都存在毒性问题且效率低下，需要大量使用才能显著提高溶解度。受最近对水增溶机制的理解的启发，该机制揭示了离子液体是强大的水增溶剂，在目前的工作中，使用香草基胆碱、没食子基胆碱和水杨基胆碱来提高两种模型药物布洛芬和萘普生的水溶解度。结果表明，香草基胆碱和没食子基胆碱能够将布洛芬的溶解度提高至 500 倍，而三种离子液体都能将萘普生的溶解度提高至 600 倍。值得注意的是，水杨基胆碱将布洛芬的溶解度提高至 6000 倍。与常规水增溶剂相比，这些结果表明基于胆碱的离子液体具有非凡的提高疏水性药物溶解度的水增溶能力，即使在稀释浓度（低于 1 mol·kg）下也是如此。由于这些离子液体的生物基性质及其低毒性特征，这些结果在药物制剂领域尤为重要。最后，结果表明，在这些新型水增溶剂中的溶解度机制取决于两亲离子之间的协同作用。
