Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systems

Aroso, Ivo Manuel Ascensão; Silva, João Carlos; Mano, Francisca; Ferreira, Ana Sofia; Dionı́sio, Madalena; Sá‐Nogueira, Isabel; Barreiros, Susana; Reis, Rui L.; Paiva, Alexandre; Duarte, Ana Rita C.

doi:10.1016/j.ejpb.2015.11.002

Cited by 180 publications

(158 citation statements)

References 21 publications

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“…To evaluate the anti-bacterial activity of mandelic acid in pure form, when part of a THEDES, and when part of a THEDES encapsulated in gelatin fibers, MIC values were determined for both Gram-positive (S. aureus) and Gramnegative bacteria (E. coli), as previously described (21). Mandelic acid displayed a MIC of 2.5 mg/mL, which is in agreement with that reported for both bacteria (37).…”

Section: Bacteriological Studysupporting

confidence: 81%

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Production of Electrospun Fast-Dissolving Drug Delivery Systems with Therapeutic Eutectic Systems Encapsulated in Gelatin

et al. 2017

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Fast-dissolving delivery systems (FDDS) have received increasing attention in the last years. Oral drug delivery is still the preferred route for the administration of pharmaceutical ingredients. Nevertheless, some patients, e.g. children or elderly people, have difficulties in swallowing solid tablets. In this work, gelatin membranes were produced by electrospinning, containing an encapsulated therapeutic deep-eutectic solvent (THEDES) composed by choline chloride/mandelic acid, in a 1:2 molar ratio. A gelatin solution (30% w/v) with 2% (v/v) of THEDES was used to produce electrospun fibers and the experimental parameters were optimized. Due to the high surface area of polymer fibers, this type of construct has wide applicability. With no cytotoxicity effect, and showing a fast-dissolving release profile in PBS, the gelatin fibers with encapsulated THEDES seem to have promising applications in the development of new drug delivery systems.

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Section: Bacteriological Studysupporting

confidence: 81%

“…This class of DES was named therapeutic deep-eutectic solvents (THEDES) (19,20). API in the form of THEDES presents higher permeability and dissolution rate than its pure form (21). In this work, it was used as gelatin fibers and mandelic acid was used as API.…”

Section: Introductionmentioning

confidence: 99%

Production of Electrospun Fast-Dissolving Drug Delivery Systems with Therapeutic Eutectic Systems Encapsulated in Gelatin

et al. 2017

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“…The eutectic phase behaviour of AVO is advantageous for its successful incorporation into simple, low-energy, bio-compatible SEDDS. Eutectic mixtures are shown to improve drug dissolution/solubility and bioavailability [40][41][42] ; however, these systems employ structurally unrelated molecules (e.g. drug and excipients) to form eutectics.…”

Section: Discussionmentioning

confidence: 99%

Avocado-derived polyols for use as novel co-surfactants in low energy self-emulsifying microemulsions

Ahmed

Kermanshahi

Ghazani

et al. 2020

Sci Rep

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Avocado (Persea americana Mill.; Lauraceae) seed-derived polyhydroxylated fatty alcohols (PFAs) or polyols (i.e., avocadene and avocadyne) are metabolic modulators that selectively induce apoptosis of leukemia stem cells and reverse pathologies associated with diet-induced obesity. Delivery systems containing avocado polyols have not been described. Herein, natural surface active properties of these polyols are characterized and incorporated into self-emulsifying drug delivery systems (SEDDS) that rely on molecular self-assembly to form fine, transparent, oil-in-water (O/W) microemulsions as small as 20 nanometers in diameter. Mechanistically, a 1:1 molar ratio of avocadene and avocadyne (i.e., avocatin B or AVO was shown to be a eutectic mixture which can be employed as a novel, bioactive, cosurfactant that significantly reduces droplet size of medium-chain triglyceride O/W emulsions stabilized with polysorbate 80. In vitro cytotoxicity of avocado polyol-SEDDS in acute myeloid leukemia cell lines indicated significant increases in potency and bioactivity compared to conventional cell culture delivery systems. A pilot pharmacokinetic evaluation of AVO SEDDS in C57BL/6J mice revealed appreciable accumulation in whole blood and biodistribution in key target tissues. Lastly, incorporation of AVO in SEDDS significantly improved encapsulation of the poorly water-soluble drugs naproxen and curcumin. Avocados have been shown to be an exclusive source of unique long carbon chain (C 17 to C 21) polyhydroxylated fatty alcohols or polyols that possess anti-cancer, anti-inflammatory and anti-microbial properties 1-4. Previously, we demonstrated that avocatin B (AVO), a 1:1 mixture of two 17-carbon polyols (avocadyne and avocadene), target mitochondria and inhibit fatty acid oxidation (FAO) which selectively induces death in leukemia cells 5-8. More recently, avocadyne has been shown to exert potent immunomodulatory effects that impede dengue virus replication in vitro 9. Furthermore, our laboratory determined that AVO inhibited FAO in skeletal muscle and pancreatic β-cells reversing insulin resistance and restoring glucose tolerance in diet-induced obesity 10. The highly promising indications for avocado polyols in human disease and nutrition necessitate the complete characterization of their physicochemical properties and subsequent development of optimal formulations for future in vivo and clinical studies. To our knowledge, use of avocado polyols is prominent in topical cosmetic formulations described briefly in patent literature 11,12. This is the first report that avocadene and avocadyne possess unique physicochemical properties ideal for SEDDS applications. SEDDS comprise a mixture of oils, co-solvents, surfactants and co-surfactants that spontaneously self-assemble into oil-in-water (O/W) or water-in-oil (W/O) nano (~100-400 nm in diameter) or micro (<100 nm in diameter) emulsions 13. Surfactants delay droplet coalescence by reducing the surface free energy associated with the oil-water interface by creating a rigid, ...

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“…Their results indicated the potential of these eutectics as dissolution enhancers in the development of novel and more effective drug delivery systems. However, their experiments were limited to in vitro trials only [31].…”

Section: Discussionmentioning

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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Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systems

Cited by 180 publications

References 21 publications

Production of Electrospun Fast-Dissolving Drug Delivery Systems with Therapeutic Eutectic Systems Encapsulated in Gelatin

Production of Electrospun Fast-Dissolving Drug Delivery Systems with Therapeutic Eutectic Systems Encapsulated in Gelatin

Avocado-derived polyols for use as novel co-surfactants in low energy self-emulsifying microemulsions

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

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