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[Display omitted] • Seven different natural deep eutectic solvents (NADES) were obtained. • The NADES were investigated as co-solvents that enhancing metronidazole (MNZ) solubility. • Choline chloride-citric acid NADES enhanced the solubility of MNZ most efficiently. • The dominating interactions between MNZ and the co-solvent were hydrophilic-hydrophobic and hydrophobic-hydrophobic. This research aimed to explore the utility of natural deep eutectic solvents (NADES) as the co-solvents for slightly water-soluble metronidazole (MNZ). After testing 70 wt% (percentage by weight) aqueous mixtures of seven NADESs, it was found that MNZ had the highest solubility in water solutions of NADES composed of choline chloride (ChCl) and citric acid (CA). The solubility of MNZ (expressed as 103 mol fraction) increased with the concentration of ChCl:CA NADES (from 6.7743 to 26.8518 at 298.5 K, for 30 and 70 wt% NADES-water mixtures, respectively), and it was more effective when compared to aqueous solutions of individual NADES components with wt% corresponding to these in the NADES-water mixtures. The study also found a preferable mixing of MNZ with aqueous solutions of NADES reflected by negative values of standard molar enthalpy change of mixing (approx. − 4.2 kJ·mol−1), compared with positive values in the case of MNZ mixing with water or ChCl aqueous solutions (approx. 7.3 kJ·mol−1). Comparative research conducted on the volume and acoustics of MNZ in water and aqueous solutions of ChCl, CA, and ChCl:CA NADES also confirmed stronger interactions between the drug and NADES and CA. The dominant interactions between MNZ and co-solvent were hydrophilic-hydrophobic and hydrophobic-hydrophobic. This effect increased in the following strength order: ChCl < NADES < CA. In conclusion, the obtained NADES seems to be a promising co-solvent which provides solid grounds for further research to evaluate the full potential in pharmaceutical design of MNZ liquid formulations. [ABSTRACT FROM AUTHOR]

This work describes a simplified method developed for calculating the Hansen parameters (HSPs) for scCO2-polar modifier solvent mixtures. The method consists in fitting 2nd order equations on the calculated values of HSPs of pure components in function of pressure and temperature. It has been proved that these equations are suitable for the characterization of the above system. The current work also proposes a modified representation method, which eliminates the shortcomings of the original ternary Teas diagram, normally used for the representation of the Hansen parameters. On the one hand, the Teas diagram uses quantities without any physical meaning and, on the other hand, the illustration of the solubility information is distorted because it does not take into account the differences of the Hildebrand parameters of different solvents. The factors we have chosen to represent on the ternary diagram possess physical meaning (cohesion energy density partitions). The distortion was eliminated by extending the Teas diagram to a prismatic three dimensional representation. We proved that the Hansen-ellipsoid from the Cartesian coordinate system (dd = f (δH, dp)) is transformed in an ellipsoid also in the new coordinate system (the transformation is pseudo-isomorphic). Nonetheless, the suggested corrections improve the accuracy of the Hansen method, in some cases the interactions between the solvents and the dissolved materials are still not predicted with sufficient accuracy. Most probably a thermodynamic-based correction of the values of the HSPs of small molecules could lead to a significant improvement of the predictive ability of the newly developed method. [ABSTRACT FROM AUTHOR]

Ferulic acid (FA) is a phenolic compound present in many natural extracts. To obtain high FA extraction yields using supercritical carbon dioxide (scCO 2 ), the extraction should be performed in the presence of co-solvents. This work reports FA solubility in scCO 2 /ethanol/water mixtures and its thermodynamic modelling using the Peng-Robinson equation of state. FA solubility in scCO 2 /ethanol was measured by a dynamic method at different temperatures (313, 323 and 333) K, pressures (20, 30 and 40) MPa and mole ratios of the scCO 2 /ethanol mixture (95:5 and 90:10). FA solubility in scCO 2 with ethanol and water was evaluated at 323 K and 30 MPa, at three different mole ratios of the scCO 2 /ethanol/water mixture (97.4:2:0.6, 93.5:5:1.5 and 88:9.3:2.7). Also measured was the solubility of FA in water and in ethanol at ambient pressure. By using 10% ethanol, the FA solubility in (scCO 2 + ethanol) attained values 120 times higher than FA solubility in pure scCO 2 and about 50 times lower than solubility in ethanol. The lowest value was obtained at 313 K and 20 MPa and the highest at 333 K and 40 MPa (1.9 × 10 −3 ); however, the co-solvent effect decreased when increasing pressure. Finally, the presence of the co-solvent is very important to obtain natural extracts rich in ferulic acid. The prediction of FA solubility in ternary and quaternary systems using the binary interaction parameters did not produce good results. Calculated values were smaller than the experimental values, probably due to the strong interactions between acid molecules and alcohol. [ABSTRACT FROM AUTHOR]

The main objective of the present study was to develop formulations of noscapine hydrochloride hydrate with enhanced solubility and bioavailability using co-solvent- and cyclodextrin-based approaches. Different combinations of co-solvents, which were selected on the basis of high-throughput solubility screening, were subjected to in vitro intestinal drug permeability studies conducted with Ussing chambers. Vitamin E tocopherol polyethylene glycol succinate and propylene glycol based co-solvent formulations provided the maximum permeability coefficient for the drug. Inclusion complexes of the drug were prepared using hydroxypropyl-β-cyclodextrin and sulphobutylether cyclodextrins. Pharmacokinetic studies were carried out in male Sprague-Dawley rats for the selected formulations. The relative bioavailabilities of the drug with the co-solvent- and cyclodextrin-based formulations were found to be similar. [ABSTRACT FROM AUTHOR]

The internal pith of a high energy plant, Elephant grass (EG), was more extensively degraded (>50% dry matter) compared to the outer cortex (31%) or the whole stem (35%) by an enzyme preparation from Humicola insolens, Ultraflo. Reducing sugars and acetic acid release from the pith was also higher compared to the cortex. Supplementation of Ultraflo with a type-C feruloyl esterase increased the level of deacetylation but also led to reduced solubilisation. The addition of 20% dimethyl sulfoxide (DMSO) as a co-solvent also reduced the solubility of EG by Ultraflo, although acetic acid release was increased, complimenting previous results found on model substrates. The presence of DMSO was also shown to have a protective effect on xylanase activity but not acetyl esterase activity in Ultraflo. Xylan in the biomass was preferentially solubilised by DMSO, while Ultraflo removed more glucose than xylose. [ABSTRACT FROM AUTHOR]

The aim of present study to enhance the solubility of quercetin, a poorly water soluble drug, quercetin containing blends (keeping total concentration 40% w/v, constant) was fabricated by mixed-solvency approach. In this technique, blends of solubilizers (sodium acetate, sodium citrate, urea as hydrotropic agent, propylene glycol, glycerin, PEG 200, PEG 400, PEG 600 as co solvents, PEG 4000, PEG 6000 as water soluble solvents etc.) have been employed to increase the solubility. The significant enhancement in solubility of drug in mixed solvents was observed in A4 blends which contain 10% sodium citrate, 5% sodium acetate and 25% S co-solvents (25% S co-solvents contains PG, glycerin, PEG 200, PEG 400, PEG 600, PEG 4000, PEG 6000). After improvement of solubility of quercetin in selected blends that incorporated into topical dosage form (prepared gel) by utilizing Carbopol ETD 2020 as gelling agent. The prepared blends and gel were evaluated for pH, surface tension, specific gravity and viscosity and in--vitro diffusion study, skin irritation studies, spreadability respectively. The characterization of pure quercetin, blend, and gel was performed by differential scanning calorimetry (DSC); X-ray diffraction (XRD) etc. From experimental work it was found that the prepared formulation is safe, effective, non-irritant, non-toxic and stable with good spreadability. The results showed that mixed solvency has valuable and unique strategy to ameliorating the solubility of lipophilic herbal anticancer component, quercetin. [ABSTRACT FROM AUTHOR]

Self-emulsifying drug delivery systems (SEDDSs) have gained exposure for their ability to increase solubility and bioavailability of poorly soluble drugs. SEDDSs are mixtures of oils, surfactants, and cosurfactants, which are emulsified in aqueous media under conditions of gentle stirring and digestive motility that are encountered in the gastrointestinal (GI) tract. We found that SEDDSs could efficiently improve oral absorption of the sparingly soluble drugs by rapid self-emulsification and, subsequently, dispersion in the absorption sites. SEDDSs possess unparalleled potential in improving oral bioavailability of poorly water soluble drugs. Following their oral administration, these systems rapidly disperse in GI fluids, yielding micro-or nanoemulsions containing the solubilized drug. Owing to its miniscule globule size, the micro/nanoemulsifed drug can easily be absorbed through lymphatic pathways, bypassing the hepatic first-pass effect. [ABSTRACT FROM AUTHOR]

Solubility enhancement of antimicrobial drug enrofloxacin has been studied using a series of co-solvents and surfactants. Aqueous solubility of enrofloxacin could be increased up to 26 times. Co-solvents alone produced only small increase in solubility. However, the combined effect of co-solvents and buffer was synergistic and a large increase in solubility could be attained. Ionic surfactants were found to be much better solubilizing agents than non-ionic surfactant. Amongst ionic surfactants, solubility was found to be very high in anionic surfactant, sodium dodecylsulphate as compared to the cationic surfactant, cetyltrimethylammonium bromide. Up to 3.8 mg/ml of enrofloxacin could be dissolved in sodium dodecylsulphate. Mechanism of solubilization has been proposed and surfactant solubilization parameters have been calculated. [ABSTRACT FROM AUTHOR]

Abstract: The use of a cyclodextrin induced inclusion complex can be very useful during the biohydrolysis of poorly soluble substrates. By using hydroxypropyl-β-cyclodextrin (HPB), the water solubility of styrene oxide (SO) was increased seven-fold (from 2.12 to 15.11g/l at 15°C) (20%, w/v) and at 10% (w/v) HPB SO was almost three times (9.71g/l at 15°C) more soluble than in 10% dimethylsulfoxide (DMSO) (w/v) (3.80g/l at 15°C). Increasing concentrations of HPB did not influence the enzymatic stability of epoxide hydrolase (EH) from Rhodotorula glutinis contrary to the organic co-solvents which negatively influenced it in the order DMSO>dimethylformamide (DMF). HPB does, however, negatively influence the EH activity of the biocatalyst R. glutinis UOFS Y-0653. When compared to the inhibition resulting from the addition of organic co-solvents, the inhibition was in the order DMF>HPB>DMSO. Inactivation constants of, 4.54±0.32, 3.29±0.28 and 1.81±0.13 (weightratio−1 w/v) were determined for DMF, HPB and DMSO, respectively. Neither DMSO nor DMF influenced the selectivity of the reaction while HPB decreased it slightly. Thermal studies yielded inactivation energy (E a) values of 84.0, 82.3 and 86.0kJ/mol for DMSO, DMF and HPB, respectively. [Copyright &y& Elsevier]

Extraction of organic binders (paraffin waxes) from injected green ceramic parts, by using supercritical fluids, has proven to be very efficient (short time of extraction, no defects in the green part). The extraction is more rapid when the binder is in the liquid state due to capillary migration but the capillary pressure could damage the ceramic green body because of development of internal stresses. In turn, extraction of the binder in solid state avoid formation of defects but the kinetics of extraction by solubilisation in supercritical carbon dioxide is reduced. An organic co-solvent can be added to supercritical CO2 in order to increase the solid paraffin molecules solubility. Polar and non polar organic co-solvents were tested and their efficiency on the solubility of the paraffin molecules were compared. The influence of the length of the chains and of the number of side groups of co-solvent molecules were examined. The extraction was also performed by adding mixed co-solvent molecules. Mixtures of polar and non polar co-solvents were introduced in supercritical CO2. Improved extraction by a factor 5 was obtained with n-hexadecane molecule as co-solvent, which represents a good compromise between destruction of the paraffin binder molecular cohesion, which requires, on one hand, large molecules, and mobility, which requires, on the other hand, small molecules. [Copyright &y& Elsevier]