Investigation on drug solubility enhancement using deep eutectic solvents and their derivatives

Li, Zheng; Lee, Ping I.

doi:10.1016/j.ijpharm.2016.04.018

Cited by 127 publications

(61 citation statements)

References 28 publications

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“…To our knowledge, no published data are available related to the in vivo effects of NADES as administration tools for bioactive constituents. These eutectics, prepared using different starting materials, can be divided into five groups, the first is based on urea (1-4), the second on polyalcohols and sugars (5-6), the third on organic acid and sugars (7)(8)(9), the fourth on organic acid and amino acid (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), and the fifth group was prepared using choline chloride, sugars and amino acid (28)(29)(30). Our results show the ability of various NADES to dissolve rutin.…”

Section: Rutin Solubility In the Different Prepared Nadesmentioning

confidence: 99%

Natural Deep Eutectic Solvents (NADES) as a Tool for Bioavailability Improvement: Pharmacokinetics of Rutin Dissolved in Proline/Glycine after Oral Administration in Rats: Possible Application in Nutraceuticals

et al. 2016

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There is a need for innovation in plant-derived pharmaceuticals, food supplements and nutraceutical products regarding the use of more eco-sustainable solvents for their extraction. Furthermore, the poor oral bioavailability of several phytochemicals with health promoting effects stimulates the research in the field of pharmaceutical formulations. Natural Deep Eutectic Solvents (NADES) are formed by natural compounds, and can be considered as future solvents being especially useful for the preparation of nutraceuticals and food-grade extracts. In this paper various NADES were prepared using sugars, aminoacids and organic acids. Rutin (quercetin-3-O-α-L-rhamnopyranosyl-(1→6))-β-D-glucopyranose) was used as a model compound to study NADES. Moreover, the effect of various eutectic mixtures on rutin's water solubility was studied. Proline/glutamic acid (2:1) and proline/choline chloride (1:1) mixtures have a solubility comparable to ethanol. The proline/glutamic acid (2:1) eutectic containing rutin was used in a pharmacokinetic study in Balb/c mice while bioavailability was compared to oral dosing of water suspension. Plasmatic levels of rutin were measured by HPLC-MS/MS showing increased levels and longer period of rutin permanence in plasma of NADES treated animals. This paper reports the possible use of non-toxic NADES for pharmaceutical and nutraceutical preparations.

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Section: Rutin Solubility In the Different Prepared Nadesmentioning

confidence: 99%

Natural Deep Eutectic Solvents (NADES) as a Tool for Bioavailability Improvement: Pharmacokinetics of Rutin Dissolved in Proline/Glycine after Oral Administration in Rats: Possible Application in Nutraceuticals

et al. 2016

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“…There are several beneficial properties of NADES which distinguish them from traditional solvents and these include low volatility, liquid state even in sub-zero temperatures, biodegradability, sustainability, high extraction and stabilization potential, low cost and simplicity of preparation ( 30 ). It is then no surprise that natural deep eutectic solvents have found their application in many different areas, such as extraction ( 31 ), stabilization ( 30 ), biotransformation ( 32 ), enzyme reactions ( 33 ), improving solubility in the aqueous phase ( 34 ) or enhancement of bioactivity ( 35 ).…”

Section: Introductionmentioning

confidence: 99%

Natural Deep Eutectic Solvents as Agents for Improving Solubility, Stability and Delivery of Curcumin

2019

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Purpose Study on curcumin dissolved in natural deep eutectic solvents (NADES) was aimed at exploiting their beneficial properties as drug carriers. Methods The concentration of dissolved curcumin in NADES was measured. Simulated gastrointestinal fluids were used to determine the concentration of curcumin and quantum chemistry computations were performed for clarifying the origin of curcumin solubility enhancement in NADES. Results NADES comprising choline chloride and glycerol had the highest potential for curcumin dissolution. This system was also successfully applied as an extraction medium for obtaining curcuminoids from natural sources, as well as an effective stabilizer preventing curcumin degradation from sunlight. The solubility of curcumin in simulated gastrointestinal fluids revealed that the significant increase of bioavailability takes place in the small intestinal fluid. Conclusions Suspension of curcumin in NADES offers beneficial properties of this new liquid drug formulation starting from excreting from natural sources, through safe storage and ending on the final administration route. Therefore, there is a possibility of using a one-step process with this medium. The performed quantum chemistry computations clearly indicated the origin of the enhanced solubility of curcumin in NADES in the presence of intestinal fluids. Direct intermolecular contacts leading to hetero-molecular pairs with choline chloride and glycerol are responsible for elevating the bulk concentration of curcumin. Choline chloride plays a dominant role in the system and the complexes formed with curcumin are the most stable among all possible homo- and hetero-molecular pairs that can be found in NADES-curcumin systems.

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“…The field of applications of natural deep eutectic solvents is very broad, and includes for example the dissolution of DNA [ 11 , 12 ], acting as media for enzyme reactions [ 23 ], biotransformations [ 24 ], biomass processing [ 25 ], the stabilization of pigments [ 16 ], and various extractions [ 26 – 29 ]. The pharmaceutical industry is another field in which NADES can be extremely useful; for instance, they can be used to improve the solubility of drugs that are poorly soluble in water [ 30 , 31 ] and to enhance the bioactivities of dissolved species [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

Application of a computational model of natural deep eutectic solvents utilizing the COSMO-RS approach for screening of solvents with high solubility of rutin

Jeliński

Cysewski

2018

J Mol Model

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The screening of natural deep eutectic solvents (NADES) to identify those with the ability to strongly solvate rutin was conducted using the COSMO-RS methodology. A NADES model was constructed that took into account the possible ionic and neutral forms of its constituents. The distributions of all forms were computed based on the equilibrium constants of neutralization reactions between amino and carboxylic acids. The proposed model was validated against the experimental solubilities of 15 NADES. A linear relationship between these data and the estimated activity coefficient values was found. The screening encompassed 126 different NADES. It was found that ten of them outperformed the best reference system. The most effective two-component solvent comprised proline combined with 2,3-diaminosuccinic acid, and the solubility of rutin in this solvent was found to be 130% greater than its solubility in the best reference system. The amino acids associated with the highest rutin solubilities were all cyclic, and the use of carboxylic acids with two carboxyl groups and a main chain consisting of two methylene groups with two amino substituents was observed to yield the best rutin solubilities. Because of the acidic properties of rutin, the presence of basic sites on the components of the NADES generally leads to enhanced solubility.Electronic supplementary materialThe online version of this article (10.1007/s00894-018-3700-1) contains supplementary material, which is available to authorized users.

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Investigation on drug solubility enhancement using deep eutectic solvents and their derivatives

Cited by 127 publications

References 28 publications

Natural Deep Eutectic Solvents (NADES) as a Tool for Bioavailability Improvement: Pharmacokinetics of Rutin Dissolved in Proline/Glycine after Oral Administration in Rats: Possible Application in Nutraceuticals

Natural Deep Eutectic Solvents (NADES) as a Tool for Bioavailability Improvement: Pharmacokinetics of Rutin Dissolved in Proline/Glycine after Oral Administration in Rats: Possible Application in Nutraceuticals

Natural Deep Eutectic Solvents as Agents for Improving Solubility, Stability and Delivery of Curcumin

Application of a computational model of natural deep eutectic solvents utilizing the COSMO-RS approach for screening of solvents with high solubility of rutin

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