Liquid pharmaceuticals formulation by eutectic formation

Abbott, Andrew P.; Ahmed, Essa I.; Prasad, Kamalesh; Qader, Idrees B.; Ryder, Karl S.

doi:10.1016/j.fluid.2017.05.009

Cited by 109 publications

(107 citation statements)

References 12 publications

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“…The current COSMO-RS parameterization seems to have problems in dealing with aromatic acids. Abbott et al [13] reported mixtures of choline chloride with acetylsalicylic acid to be liquid at room temperature but using dry compounds this could never be achieved in our study, the actual eutectic temperature observed are well above room temperature. COSMO-RS can in general provide semi-quantitative predictions that can be useful for scanning a large number of systems, selecting a solvent or, as shown in this work, the melting temperature of a mixture.…”

Section: Design Of Novel Pharmaceutical-based Eutectic Solventscontrasting

confidence: 68%

Using COSMO-RS to design choline chloride pharmaceutical eutectic solvents

Abranches

Larriba

Silva

et al. 2019

Fluid Phase Equilibria

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a b s t r a c tDeep eutectic solvents (DES) present interesting properties, mostly connected to their solvation ability, and have been subject to much research in the recent past. Currently, the discovery of new eutectic solvents is accomplished by experimentally measuring the eutectic point of random systems, often using choline chloride as a hydrogen bond acceptor. In this work, the eutectic temperatures of new choline chloride-based eutectic systems were experimentally assessed. These data, along with other previously reported in the literature, were used to evaluate a method based on COSMO-RS to predict the eutectic temperature of choline-chloride based mixtures. The predictive methodology herein developed allows for the quick scanning of a large matrix of systems in order to identify those more promising to be in the liquid state at a given temperature. To validate this method, the eutectic temperature of pharmaceutical drug mixtures was predicted and, then, assessed experimentally, showing that COSMO-RS is useful in the design of liquid drug-based formulations.

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Section: Design Of Novel Pharmaceutical-based Eutectic Solventscontrasting

confidence: 68%

Using COSMO-RS to design choline chloride pharmaceutical eutectic solvents

Abranches

Larriba

Silva

et al. 2019

Fluid Phase Equilibria

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“…50−53 In view of the above, we pursued the chemical synthesis and in vitro evaluation of the antiproliferative properties of PQ, CQ, and MP betulinates. Trihexyltetradecylphosphonium ([P 6,6,6,14 ]) betulinate was also produced, based on the longknown anticancer potential of phosphonium salts. 33−37 Hopefully, a combination of the betulinate anion with organic cations, as the protonated forms of the aforementioned antimalarial drugs or the trihexyltetradecylphosphonium cation, might deliver organic salts with improved solubility, and a synergetic effect against tumor cell lines.…”

Section: Introductionmentioning

confidence: 99%

“…1, 28 The target organic salts derived from BA and the antimalarial drugs [ Figure 3a) were thus synthesized by the neutralization method, as previously reported, 28 whereby each of the basic antimalarials was reacted with an equimolar amount of BA. 1, 28 For the chemical synthesis of [P 6,6,6,14 ][BA] (Figure 3b), the commercially available chloride salt [P 6,6,6,14 ][Cl] was converted into the hydroxide, using an Amberlyst anion exchange resin (A26-OH), prior to the neutralization reaction with BA. These procedures delivered the target ionic compounds in quantitative yields (Table 1) and free of detectable impurities, as confirmed by high-resolution mass spectrometry (HRMS) and by 1 H and 13 C NMR (see the Supporting Information).…”

Section: Introductionmentioning

confidence: 99%

“…0.9 ppm, integrating to 12 protons) from the trihexyltetradecylphosphonium cation (see the Supporting Information). Notably, as shown in Table 1, all but [P 6,6,6,14 ][BA] were solid at room temperature, evidencing relatively high melting points, which were apparently accompanied by decomposition (drastic change in compound color at the melting temperature). In turn, [P 6,6,6,14 ][BA] was a room-temperature IL.…”

Section: Introductionmentioning

confidence: 99%

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Antiproliferative Organic Salts Derived from Betulinic Acid: Disclosure of an Ionic Liquid Selective Against Lung and Liver Cancer Cells

Silva

Cerqueira²,

Prudêncio

et al. 2019

ACS Omega

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In the last few years, we have been witnessing an increasing interest in ionic liquids (ILs) and organic salts, given their potential applications in biological and pharmaceutical sciences. We report the synthesis and in vitro evaluation of novel organic salts combining betulinate, known for its anticancer properties, with antimalarial drugs, primaquine, chloroquine, and mepacrine, and also with the trihexyltetradecylphosphonium ([P 6,6,6,14 ]) cation. The salts were screened for their in vitro activity against tumor lines HepG2 (liver), MG63 (osteosarcoma), T47D (breast), A459 (lung), and RKO (colon), and also on normal human fibroblasts. All betulinates prepared displayed antiproliferative properties, with the trihexyltetradecylphosphonium betulinate standing out for its higher selectivity. This unprecedented disclosure of a betulinic acid (BA)-derived IL with selective antitumor activity constitutes a relevant first step toward development of novel anticancer therapies based on BA-derived IL. (1) Ferraz, R.; Branco, L. C.; Marrucho, I. M.; Araujo, J. M. M.; Rebelo, L. P. N.; da Ponte, M. N.; Prudencio, C.; Noronha, J. P.; Petrovski, Z. Development of novel ionic liquids based on ampicillin. MedChemComm 2012, 3, 494−497. (2) Ferraz, R.; Branco, L. C.; Prudencio, C.; Noronha, J. P.; Petrovski, Z. Ionic Liquids as Active Pharmaceutical Ingredients. ChemMedChem 2011, 6, 975−985. (3) Ferraz, R.; Costa-Rodrigues, J.; Fernandes, M. H.; Santos, M. M.; Marrucho, I. M.; Rebelo, L. P. N.; Prudencio, C.; Noronha, J. P.; Petrovski, Z.; Branco, L. C. Antitumor Activity of Ionic Liquids Based on Ampicillin.

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“…As a result, the product needs no further purification. DESs have been applied in catalytic reaction, material preparation, synthesis processes, biomass pre‐treatment, and extraction processes …”

Section: Introductionmentioning

confidence: 99%

Effective separation of aromatic hydrocarbons by pyridine‐based deep eutectic solvents

et al. 2019

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Many promising qualities of deep‐eutectic solvents made them suitable solvents in separation process. In this work, the pyridine‐based deep eutectic solvents were designed and synthesized with N‐ethylpyridinium bromide and two HBDs (N‐formyl morpholine and levulinic acid). Two ternary systems, benzene + cyclohexane + DES and toluene + n‐heptane + DES, were studied by the liquid‐liquid extraction. The effect of different HBDs, extraction time, volume ratio of DES to system solution, and the initial concentration of aromatic were studied. The DES with N‐formyl morpholine showed better separation performance than that with levulinic acid. The liquid‐liquid extraction equilibrium could be obtained in 10 minutes. The volume ratio of DES to system solution was set as 1:1. Both DESs showed their best separation performance at low temperatures (20°C) and low aromatic concentration system. For the benzene + cyclohexane system, the distribution coefficient of benzene was 1.733 and the selectivity was 23.8 at 20°C. For the toluene + n‐heptane system, the distribution coefficient of toluene was 0.853 and the selectivity was 40.7. Tie‐lines for two ternary systems were obtained, and the Othmer‐Tobias correlation was used to check the reliability of the obtained liquid‐liquid extraction experimental data. The experimental LLE data were correlated using the NRTL model and the calculated data correlated significantly with the experimental data.

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Liquid pharmaceuticals formulation by eutectic formation

Cited by 109 publications

References 12 publications

Using COSMO-RS to design choline chloride pharmaceutical eutectic solvents

Using COSMO-RS to design choline chloride pharmaceutical eutectic solvents

Antiproliferative Organic Salts Derived from Betulinic Acid: Disclosure of an Ionic Liquid Selective Against Lung and Liver Cancer Cells

Effective separation of aromatic hydrocarbons by pyridine‐based deep eutectic solvents

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