A novel water-in-ionic liquid microemulsion and its interfacial effect on the activity of laccase

It is of great significance to develop an appropriate water-in-ionic liquid (W/IL) microemulsion suitable for the expression of the catalytic activity of a given enzyme. In this paper, the phase diagram of a new AOT/Triton X-100/H(2)O/[Bmim][PF(6)] pseudo ternary system is presented. With the aid of nonionic surfactant Triton X-100, AOT could be dissolved in hydrophobic ionic liquid [Bmim][PF(6)], forming a large single phase microemulsion region. The water-in-[Bmim][PF(6)] (W/IL) microemulsion domain was identified electrochemically by using K(3)Fe(CN)(6) as a probe. The existence of W/IL microemulsions was demonstrated spectrophotometrically by using CoCl(2) as a probe. New evidences from the FTIR spectroscopic study, which was first introduced to the W/IL microemulsion by substituting D(2)O for H(2)O to eliminate the spectral interference, demonstrated that there existed bulk water at larger ω(0) values (ω(0) was defined as the molar ratio of water to the total surfactant) in the W/IL microemulsion, which had remained unclear before. In addition to the inorganic salts, biomacromolecule laccase could be solubilized in the W/IL microemulsion. The laccase hosted in the microemulsion exhibited a catalytic activity and the activity could be regulated by the composition of the interfacial membrane.     

Tween80/BmimPF6/醇/甲苯体系的相行为

以环境友好型的Tween80为表面活性剂, 以醇(乙醇、正丁醇、正己醇、正辛醇、正癸醇和异戊醇)为助表面活性剂, 对离子液体1-丁基-3-甲基咪唑六氟磷酸盐(bmimPF6)和甲苯进行了微乳化实验, 绘制了不同条件下Tween80离子液体的微乳体系的拟三元相图, 考察了醇的种类、含量对单相微乳区的影响, 并用电导法研究了在乙醇为助表面活性剂情况下, 单相微乳区的结构转变. 结果表明, 当醇(异戊醇)固定时, 随着表面活性剂/醇的质量比增加, 单相微乳区的面积逐渐增大; 不同链长的直链醇对单相微乳区的面积影响与该醇在离子液体中的溶解情况有关, 单相微乳区的面积随着直链醇链长的增加而越小; 当乙醇作助表面活性剂时, 所得到的单相微乳区的面积最大, 且单相微乳区存在着O/IL(oil-in-ionic liquid)、双连续相和IL/O(ionic liquid-in-oil)三种微结构. 尤其对离子液体微乳体系的电导随油的含量的增加而最初增大的现象进行了解释, 这一现象是由于油主要起到减少离子液体中离子对或离子的积聚, 提高带电离子淌度的作用.     

Synergistic Effect of Mixed Cosurfactants on Transdermal Delivery of Indomethacin from O/W Microemulsion

Since large amounts of oils, surfactants and penetration enhancers used in microemulsion systems might lead to seriously skin irritation, the percutaneous absorption and penetration of indomethacin(IMC, model drug) from O/W microemulsion were enhanced by simply changing the composition of cosurfactants. Pseudo-ternary phase diagrams were constructed with mixed cosurfactants at different ratios. Hairless rat skin was used as a barrier for permeation experiments. Four formulations were prepared with fixed oil, surfactant and different cosurfactant content(4%, 20% and 20%, mass fraction), and formulation F4 with menthol added was evaluated to compare the enhancement effect of it with those of mixed cosurfactants. The O/W microemulsion region was the largest when the mass ratio of ethanol/transcutol was 1:1. However, the region changed slightly for the system with incorporated mixed cosurfactants propylene glycol/transcutol. The flux and skin retention of IMC from O/W microemulsion with mixed cosurfactants were much higher than that with single cosurfactant(P<0.01), while incorporation of menthol would only enhance the drug flux through the skin. To conclude, mixed cosufactants could affect the phase behavior and improve the percutaneous absorption and penetration of IMC. Based on this, it provided a promising solution to enhance drug release from microemulsions without raising potential skin damage.     

Dramatic Change in Viscosities of Pure Ionic Liquids upon Addition of Molecular Solvents

Viscosities of binary mixtures of pyridinium based ionic liquids (1-butyl pyridinium tetrafluoroborate, [BP][BF₄], 1-butyl 3-methyl pyridinium tetrafluoroborate [3-MBP][BF₄], 1-butyl 4-methyl pyridinium tetrafluoroborate, [4-MBP][BF₄]), and phosphonium based ionic liquids, (tetrabutyl phosphonium alaninate, [TBP][Ala]; tetrabutyl phosphonium valinate, [TBP][Val]) with the molecular solvents, water, methanol and dichloromethane, have been measured at 298.15 K. A Brookfield ultra-rheometer was employed to measure the reported viscosities. The drop in viscosity in the close vicinity of pure ionic liquid is more prominent in polar solvents like water compared to less polar solvents. The temperature dependence of this observation was also studied for binary mixtures of [4-MBP][BF₄] with water in range of 298.15–323.15 K. The Vogel-Fulcher-Tamman (VFT) equation was employed to investigate the temperature dependence of the viscosities of pure pyridinium-based ionic liquids in the temperature range from 298.15–323.15 K.     

Surface tension of binary mixtures of imidazolium and ammonium based ionic liquids with alcohols, or water: cation, anion effect

The surface tensions were measured at atmospheric pressure, with use of a ring tensiometer, of a series of alcoholic solutions of closely related ionic liquids: 1-methyl-3-methylimidazolium methylsulfate, [MMIM][CH3SO4] in alcohol (methanol, or ethanol, or 1-butanol at 298.15 K), 1-butyl-3-methylimidazolium methylsulfate, [BMIM][CH3SO4] in alcohol (methanol, or ethanol, or 1-butanol at 298.15 K), 1-butyl-3-methylimidazolium octylsulfate, [BMIM][OcSO4] in alcohol (methanol, or 1-butanol at 298.15 K) and of 1-hexyloxymethyl-3-methylimidazolium tetrafluoroborate, [C6H(13)OCH2MIM][BF4], 1,3-dihexyloxymethylimidazolium tetrafluoroborate, [(C6H13OCH2)2IM][BF4] in alcohol (methanol, or 1-butanol, or 1-hexanol at 308.15 and 318.5 K) and hexyl(2-hydroxyethyl)dimethylammonium bromide, C6Br in 1-octanol at 298.15 K. The set of ammonium ionic liquids of different cations and anions (C2Br, C2BF4, C2PF6, C2N(CN)2, C3Br, C4Br and C6Br) was chosen to show the influence of small amount of the ammonium ionic liquid on the surface tension of water at 298.15 K. The influence of the cation, or anion alkyl chain length on the properties under study (densities and surface tension) was tested.     

On the incorporation of the non-steroidal anti-inflammatory naproxen into cationic O/W microemulsions

Microemulsions (ME) containing hexadecyltrimethylammonium bromide (HTAB)/ethanol as surfactant, isopropylmyristate (IM) or butylstearate (BS) as oil phase and aqueous buffer were studied. Pseudo-ternary phase diagrams of the investigated systems were obtained at constant surfactant/cosurfactant molar ratio (1:5) by titration in order to characterize the proportions between the components to obtain clear systems. Oil in water microemulsions were prepared in a wide range of phase volume (phi). UV-vis absorption spectra of naproxen at pH 5.5 showed that the solubility of Np increases significantly in the presence of O/W ME in high phase volumes. For both, IM and BS microemulsions, the dynamic light scattering experiments showed that the size of the oil droplets remains constant in low values of phi, increasing abruptly in high phi values. Phase solubility study revealed that for both IM and BS microemulsions, the drug incorporation followed a straight-line profile in all range of phi. The data could be analyzed through the phase-separation model and the association constants (K) calculated varied from 27 to 90 M(-1), depending on the pH and on the microemulsion oil phase.     

Crystallization of Celecoxib in Microemulsion Media

Celecoxib belongs to a new NSAID family specifically inhibiting cyclooxygenase‐2 (COX‐2). The present formulations require high dosage since the transmembrane transport fluctuates and is very difficult to control. We solubilized celecoxib in micelles of nonionic microemulsions and hydrophilic surfactant. The supersaturated solubilized drug was precipitated from the nano‐droplets to form a new solid structure with improved dissolution properties. The selected microemulsion systems loaded with celecoxib were characterized by SAXS, SD‐NMR, viscosity, and electrical conductivity techniques. Precipitation was conducted from W/O as well as from O/W U‐type microemulsions. The crystals obtained by the precipitation were characterized by x‐ray powder scattering, differential scanning calorimetry, FTIR measurements, and microscopic scans.     

Nonaqueous microemulsion-containing ionic liquid [bmim][PF6] as polar microenvironment

The phase behavior of toluene/Triton X-100 (TX-100)/1-butyl-3-methylimidazolium hexafluorophosphate([bmim][PF6]) was studied. It was demonstrated that the single-phase microemulsion area covered about 75% of the phase diagram at 25 °C. Electrical conductivities of the system with different w ([bmim][PF6]-to-TX-100 molar ratio) values were determined, and the results were used to locate the sub-regions of the single-phase microemulsion. The results showed that a transform from [bmim][PF6]-in-oil ([bmim][PF6]/O) microstructure via a bicontinuous region to an oil-in-[bmim][PF6] (O/[bmim][PF6]) microstructure occurred with the increase of Φ (weight fraction of TX-100 and [bmim][PF6] in the system). The aggregate size of the reverse microemulsions of [bmim][PF6]/O was determined using small-angle X-ray scattering. The results showed that the size of the reverse microemulsions depended markedly on the w values.     

Microemulsions of Potassium Oleate,Tween-20, Propylene Carbonate,and Ethylene Glycol as Drug Vehicles for Mefenamic Acid

Different microemulsions were prepared with and without mefenamic acid (MFA). The base microemulsion was mainly composed of distilled water; the aqueous phase, propylene carbonate; the oil phase, potassium oleate; the surfactant, and finally di-ethylene glycol; the cosurfactant. The effect of mixing ionic (potassium oleate) with nonionic (Tween-20) surfactant was investigated via constructing the phase diagrams of such systems. Changes in conductivity and viscosity of the freshly prepared microemulsion over time were monitored as an indication for the stability of the microemulsion. Measurements were carried out at room temperature, after a freeze-thaw cycle and also after storage for 3 days at 60°C, where the latter is treated as an accelerated test for the time-temperature effects on the stability of a microemulsion. It was found that a set of surfactants, instead of a single surfactant, and inclusion of cosurfactant resulted in a broader region where a stable microemulsion is predominant. At a mass ratio of 1:2 of potassium oleate to Tween-20, O/W microemulsions were found to have maximum stability among all examined systems, under the accelerated test, such that they have a minimum portion of combined surfactants and cosurfactant of 60 wt% and maximum of 80 wt%. With the aforementioned specifications, no phase separation and neither significant change in the conductivity nor in the viscosity was observed in any of the examined systems after subjecting them both to the accelerated and freeze-thaw cycle test, indicating that such systems were thermodynamically stable. Samples of micro emulsions passing previous tests were further subjected to an acidic medium by dispersing 1 g of MFA-containing microemulsion in 10 g HCl solution (pH 1) in a shaking water bath at 37°C, for a 6 hour period. The maximum solubility of MFA in a stable microemulsion was approximately 5 wt%, evaluated at room temperature.     

Preparation and in vitro Release Test of Insulin Loaded W/O Microemulsion

A W/O microemulsion of Tween‐80‐Span‐80/n‐butylalcohol/ethyl‐oleate/H₂O to envelop insulin (INS) was prepared. In order to obtain the maximum solved water, the components of microemulsion to envelop INS were chosen with the pseudo‐ternary phase diagram and the influences of temperature, salinity as well as the pH on microemulsion areas also were investigated. To test the properties of the microemulsion, the conductance was used to divide O/W, W/O and BC regions, the dynamic light scattering to evaluate the particle diameters of microemulsion, the ¹²⁵I isotope tracing method to measure the release rate of INS loaded in W/O microemulsion, and the growth inhibitory effect test to appraise the cytotoxicity on human normal cells. Results show that W/O microemulsion forms when water content below 50% in the microemulsion system. The microemulsion region decreases slightly with the increase of temperature, salinity and the decrease of pH. However, the viscosity measurements along certainly selected dilution lines to the microemulsion indicate that no phase invert occurred. Diameter of microemulsion particle increases with the addition of INS, and the increase is sharp in the first 5 days then very slightly at 68.6 nm within a month. The INS loaded W/O microemulsion possesses eminent sustaining release efficiency and the cytostatic as well as cytotoxic assays illustrate that the microemulsion can be used as drug delivery at small dosage.     

Interaction of ionic liquid with water with variation of water content in 1-butyl-3-methyl-imidazolium hexafluorophosphate ([bmim][PF6])/TX-100/water ternary microemulsions monitored by solvent and rotational relaxation of coumarin 153 and coumarin 490

The interaction of water with room temperature ionic liquid (RTIL) [bmim][PF6] has been studied in [bmim][PF6]/TX-100/water ternary microemulsions by solvent and rotational relaxation of coumarin 153 (C-153) and coumarin 490 (C-490). The rotational relaxation and average solvation time of C-153 and C-490 gradually decrease with increase in water content of the microemulsions. The gradual increase in the size of the microemulsion with increase in w0 (w0=[water]/[surfactant]) is evident from dynamic light scattering measurements. Consequently the mobility of the water molecules also increases. In comparison to pure water the retardation of solvation time in the RTIL containing ternary microemulsions is very less. The authors have also reported the solvation time of C-490 in neat [bmim][PF6]. The solvation time of C-490 in neat [bmim][PF6] is bimodal with time constants of 400 ps and 1.10 ns.     

Phase behaviour of 1-methyl-3-octylimidazolium bis[trifluoromethylsulfonyl]imide with thiophene and aliphatic hydrocarbons: The influence of n-alkane chain length

This paper reports the results of a new experimental study on the capacity of an ionic liquid to extract a sulfur compound from its mixtures with aliphatic hydrocarbons. With this aim, liquid + liquid equilibrium data of ternary systems containing 1-methyl-3-octyl-imidazolium bis(trifluoromethylsulfonyl)-imide ([C₈mim][NTf₂]), thiophene and n-hexane, n-heptane or n-hexadecane have been determined at T = 298.15 K. All systems showed high solubility of thiophene in the ionic liquid and low solubility of the ionic liquid in the n-alkane. The solute distribution coefficient decreases and the selectivity increases as the chain length of n-alkane increases. Both parameters are higher than unity in most of the cases. The experimental results have been correlated using NRTL activity coefficient model, and large deviations from experimental data have been found at high concentrations of thiophene with the heaviest hydrocarbons.     

SDS/正戊醇-二甲苯-水(盐水)拟三元体系相图和电导研究及纳米ZnO的制备

实验绘制了十二烷基硫酸钠(SDS)/正戊醇(n-C₅H₁₀OH)-二甲苯[C₆H₄(CH₃)₂]-水[或Zn(NO₃)₂溶液]四组分微乳液体系在不同温度时的拟三元相图. 测定了电导率随水(或盐溶液)含量变化的规律, 电导的规律与相图吻合. 依据电解质理论探讨了微乳液的微观结构, 研究表明, 温度对油包水(W/O)反相微乳液区域影响不大, 电解质的加入对油包水(W/O)反相微乳液区域影响较大. 通过SDS/正戊醇-二甲苯-H₂O及SDS/正戊醇-二甲苯-盐水的拟三元体系的相图观察及实验研究, 选择乳化剂(SDS/正戊醇)与二甲苯质量比为4:6的微乳液作为最佳条件, 制备出了ZnO纳米粒子.     

Interaction of ionic liquid with water in ternary microemulsions (Triton X-100/water/1-butyl-3-methylimidazolium hexafluorophosphate) probed by solvent and rotational relaxation of coumarin 153 and coumarin 151

The interaction of ionic liquid with water in 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6])/Triton X-100 (TX-100)/H2O ternary microemulsions, i.e., "[bmim][PF6]-in-water" microregions of the microemulsions, has been studied by the dynamics of solvent and rotational relaxation of coumarin 153 (C-153) and coumarin 151 (C-151). The variation of the time constants of solvent relaxation of C-153 is very small with an increase in the [bmim][PF6]/TX-100 ratio (R). The rotational relaxation time of C-153 also remains unchanged in all micremulsions of different R values. The invariance of solvation and rotational relaxation times of C-153 indicates that the position of C-153 remains unaltered with an increase in R and probably the probe is located at the interfacial region of [bmim][PF6] and TX-100 in the microemulsions. On the other hand, in the case of C-151, with an increase in R the fast component of the solvation time gradually increases and the slow component gradually decreases, although the change in solvation time is small in comparison to that of microemulsions containing common polar solvents such as water, methanol, acetonitrile, etc. The rotational relaxation time of C-151 increases with an increase in R. This indicates that with an increase in the [bmim][PF6] content the number of C-151 molecules in the core of the microemulsions gradually increases. In general, the solvent relaxation time is retarded in this room temperature ionic liquid/water-containing microemulsion compared to that of a neat solvent, although retardation is very small compared to that of the solvent relaxation time of the conventional solvent in the core of the microemulsions.     

Binary,ternary and microencapsulated celecoxib complexes with β-cyclodextrin formulated via hydrophilic polymers

Cyclodextrins are cyclic oligosaccharides, capable of forming inclusion complexes with many active substances. This way, the aqueous solubility and rate of dissolution of active substances can be changed. For this research we have selected celecoxib as the model active substance, due to its low water solubility, high lipophilicity, and high intestinal permeability. Usually, the amount of cyclodextrin complex that can be incorporated into a pharmaceutical dosage form is limited. The usage of hydrophilic polymers can overcome this problem. In this study, we wanted to point out the potential of various types of hydrophilic polymers for enhancing the complex formation efficiencies, and to highlight the possible use of alginate as a solubility stabilizer/enhancer and as a microsphere matrix polymer. The phase solubility investigation showed greater stability constants (> 250 M^?1) in ternary complexes than in the binary complex, which is a good indicator of the complex formation enhancer properties of these hydrophilic polymers. The relative solubilizing efficiency decreased in the next order: PVP K25 (6.49) > Sodium alginate (6.26) > PEG 6000 (5.72) > without polymer (4.81). The DSC curves showed that all samples that were prepared with β-cyclodextrin (both complexes and physical mixtures) had lower melting endotherms at 160 °C than pure celecoxib. XRD confirmed the complex formation by partial celecoxib amorphisation. The dissolution studies of the prepared microspheres revealed that all samples had different release rates (shown by the similarity factor f₂, which was 36.37, 42.46 and 38.11 % respectively) and that the use of β-cyclodextrin increased the dissolution rate of celecoxib from alginate microspheres in a controlled manner. We concluded that sodium alginate could act as a complex stabilizing/enhancing agent and as a microsphere matrix polymer, at the same time.     

Thermodynamic Properties of Binary Mixtures of the Amino Acid Ionic Liquids [Bmim][Glu] or [Bmim][Gly] with Methanol at T=298.15 to 313.15 K

Densities, viscosities and refractive indices were determined for two ionic liquid mixtures formed by the 1-butyl-3-methylimidazolium glutamic acid salt ([Bmim][Glu]) or the 1-butyl-3-methylimidazolium glycine acid salt ([Bmim][Gly]), respectively, with methanol over the mole fraction from 0.1 to 0.9 and at temperatures ranging from 298.15 K to 313.15 K at intervals of 5 K and at atmospheric pressure. Excess molar volumes, viscosity deviations and refractive index deviations have been calculated from the experimental data and fitted to a Redlich–Kister polynomial function. The results have been interpreted in terms of ion-dipole interactions, and structural factors of the ionic liquid and alcohol molecular liquids.     

Thermodynamic modeling of hydrogen sulfide solubility in ionic liquids using modified SAFT-VR and PC-SAFT equations of state

Equations of state based on the statistical associating fluid theory for potentials of variable range (SAFT-VR) and the perturbed chain statistical associating fluid theory (PC-SAFT) have been used to model the PVT behavior of ionic liquids and the solubility of H₂S in six imidazolium-based ionic liquids. The studied systems included [bmim][PF6], [hmim][PF6], [bmim][BF4], [hmim][BF4], [bmim][NTF2] and [hmim][NTF2] at various temperatures and pressures.For pure components, parameters of the models have been obtained by fitting the models to experimental data on liquid densities; the average relative deviation between the calculated and experimental densities for ionic liquids is less than 2.42% in the PC-SAFT model and 5.44% in the SAFT-VR approach, the latter which incorporates the square-well potential for short-range interactions. In both models an additional term has been added to account for dipole-dipole interactions between solute molecules resulting from the permanent charges on the chain molecules of the solvents. The model parameters have also been correlated as functions of the molecular weight of the solvents. For binary mixtures of ionic liquids and H₂S, the association interactions between H₂S molecules and between the ionic liquids and H₂S molecules have also been taken into account in both approaches, using binary interaction coefficients. The results show an average deviation of less than 5% in the calculation of the mole fraction of H₂S in the ionic liquids. The effect of inclusion of the polar term has been studied for binary systems in both models.     

Solubility of CO2, CO, and H2 in the ionic liquid [bmim][PF6] from Monte Carlo simulations

This work reports predictions from molecular simulation results for the solubility of the single gases carbon dioxide, carbon monoxide, and hydrogen in the ionic liquid 1-N-butyl-3-methyl-imidazolium hexafluorophosphate ([bmim][PF6]) at temperatures from 293 to 393 K and at pressures up to 9 MPa. The predictions are achieved by Gibbs ensemble Monte Carlo simulations at constant pressure and temperature (NpT-GEMC). The intermolecular forces are approximated by effective pair potentials for the pure gases and by a quantum-chemistry-based pair potential for [bmim][PF6]. The interactions between unlike groups are described using common mixing rules without any adjustable binary interaction parameter. The simulation results for the solubility of hydrogen agree within their statistical uncertainty with experimental data, whereas the results for carbon monoxide and carbon dioxide reveal somewhat larger deviations.     

Study on the Conductivities of Pure and Aqueous Bromide-Based Ionic Liquids at Different Temperatures

Electrical conductivities were measured for the pure ionic liquids [C₆mim][Br] (1-hexyl-3-methylimidazolium bromide) and [C₈mim][Br] (1-octyl-3-methylimidazolium bromide) at 0.1 MPa from 293.15 to 333.15 K. Conductivity measurements were also made for the binary water + [C₆mim][Br] and water + [C₈mim][Br] systems and their ternary water + [C₆mim][Br] + [C₈mim][Br] system at 0.1 MPa and 293.15, 298.15, and 303.15 K. The conductivity data of the pure ionic liquids were correlated by the VFT (Vogel-Tamman-Fulcher) equation, and the fitting parameters and mean absolute deviations were determined. New explanations are presented for the molality-dependent behavior of the conductivity of the binary water + [C₆mim][Br] and water + [C₈mim][Br] systems. The generalized Young’s rule and the semi-ideal solution theory for conductivity were used to predict the conductivities of the ternary water + [C₆mim][Br] + [C₈mim][Br] system from the conductivities of its corresponding binary water + [C₆mim][Br] and water + [C₈mim][Br] subsystems. The predictions are in good agreement with the measured values.     

CTAB/正丁醇-正辛烷-水和盐水的拟三元体系相图及微乳液微观结构的电导研究

绘制了CTAB/正丁醇-正辛烷-水和Al(NO₃)3(或Na2WO4)盐水拟三元体系的35℃相图.用电导法并结合电解质理论讨论了微乳液的微观结构,将整个微乳液单相区分为W/O微乳区、O/W微乳区和B.C.双连续区,并且用渗滤理论确定了一个分散相质点为W/O球状结构的反胶团微乳液区.