Solubility and Stability of Some Pharmaceuticals in Natural Deep Eutectic Solvents-Based Formulations.

Natali Rianika Mustafa, Vincent Simon Spelbos, Geert Jan Witkamp, Robert Verpoorte, Young Hae Choi

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Some medicines are poorly soluble in water. For tube feeding and parenteral administration, liquid formulations are required. The discovery of natural deep eutectic solvents (NADES) opened the way to potential applications for liquid drug formulations. NADES consists of a mixture of two or more simple natural products such as sugars, amino acids, organic acids, choline/betaine, and poly-alcohols in certain molar ratios. A series of NADES with a water content of 0-30% (w/w) was screened for the ability to solubilize (in a stable way) some poorly water-soluble pharmaceuticals at a concentration of 5 mg/mL. The results showed that NADES selectively dissolved the tested drugs. Some mixtures of choline-based NADES, acid-neutral or sugars-based NADES could dissolve chloral hydrate (dissociated in water), ranitidine·HCl (polymorphism), and methylphenidate (water insoluble), at a concentration of up to 250 mg/mL, the highest concentration tested. Whereas a mixture of lactic-acid-propyleneglycol could dissolve spironolacton and trimethoprim at a concentration up to 50 and 100 mg/mL, respectively. The results showed that NADES are promising solvents for formulation of poorly water-soluble medicines for the development of parenteral and tube feeding administration of non-water-soluble medicines. The chemical stability and bioavailability of these drug in NADES needs further studies.
Original languageEnglish (US)
Pages (from-to)2645
JournalMolecules (Basel, Switzerland)
Issue number9
StatePublished - May 5 2021

Bibliographical note

KAUST Repository Item: Exported on 2021-05-07
Acknowledgements: This work was possible through a collaboration with Tiofarma, Oud-Beijerland, The Netherlands, and a Horizon Valorization Project Grant (93515516) from Netherlands Genomics Initiative.

ASJC Scopus subject areas

  • Organic Chemistry


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