An Investigation of the Reuse of Liquid Membranes and the Use of a Multidrug Donor Phase in Solute Transport

Abstract

Complex or multiple emulsions have been investigated for their potential use in pharmaceutics as both drug delivery and drug removal systems. Studies involving previously unused emulsions and single drug donor phases have been described in the literature. The subsequent uptake of solutes using one multiple emulsion or liquid membrane and the co-uptake of solutes from one donor phase were studied. The ability of liquid membranes to remove one solute following removal of another solute was studied for three systems using salicylic acid and phenobarbital at various temperatures. In each case it was observed that the liquid membrane was capable of subsequent drug uptake to varying degrees indicating that the previous use of liquid membranes does not materially affect their further use as sinks. The removal of two drugs from one donor phase using a liquid membrane was studied using acetylsalicylic acid, salicylic acid, and phenobarbital. These systems demonstrated the ability to remove two solutes simultaneously at rates which were of the same magnitude as those measured in single solute systems. The solute combination, initial molar concentration of each solute, and the liquid membrane oil/water ratio were found to influence the apparent rate constants and extent of removal for each drug in the donor phase.     

Removal of phenols from aqueous solutions by emulsion liquid membranes

The present study deals with the extraction of phenols from aqueous solutions by using the emulsion liquid membranes technique. Besides phenol, two derivatives of phenol, i.e., tyrosol (2-(4-hydroxyphenyl)ethanol) and p-coumaric acid (4-hydroxycinnamic acid), which are typical components of the effluents produced in olive oil plants, were selected as the target solutes. The effect of the composition of the organic phase on the removal of solutes was examined. The influence of pH of feed phase on the extraction of tyrosol and p-coumaric was tested for the membrane with Cyanex 923 as an extractant. The use of 2% Cyanex 923 allowed obtaining a very high extraction of phenols (97-99%) in 5-6 min of contact time for either single solute solutions or for their mixtures. The removal efficiency of phenol and p-coumaric acid attained equivalent values by using the system with 2% isodecanol, but the removal rate of tyrosol was found greatly reduced. The extraction of tyrosol and p-coumaric acid from their binary mixture was also analysed for different operating conditions like the volume ratio of feed phase to stripping phase (sodium hydroxide), the temperature and the initial concentration of solute in the feed phase.     

Partition coefficients of environmentally important phenols in a supercritical carbon dioxide-water system from cocurrent extraction without analysis of the compressible phase

Partition coefficients of phenol, salicylic acid, and several environmentally important chloro- and nitrophenols in a supercritical CO2-water system were measured using direct cocurrent extraction of aqueous solutions of the individual solutes with CO2. Partitioning data on the nitrophenols and salicylic acid were obtained for the first time. To bypass the troublesome and error-prone analysis of the CO2-rich phase, the present method employed only the solute concentrations in the aqueous phase before and after extraction to determine the partition coefficient. Unlike most previous engineering studies of phenol partitioning in a CO2-water system, the concentrations of phenolic solutes approached infinite dilution in both phases. This makes the results relevant to analytical-scale SFE of environmental water samples with CO2. Because of effective infinite dilution of the solutes, the partition coefficients provide a direct measure of relative CO2-philicity/hydrophilicity of the individual phenols. Compared to the octanol-water partition coefficients of substituted phenols, the CO2-water partition coefficients are more sensitive to substitution in the position neighboring the hydroxyl group.     

Alternating voltage capillary electrochromatography

A phenomenon was found whereby the application of an alternating voltage to a capillary column can vary the capacity factor of a sample solute. The alternating voltage-induced variation in the capacity factor was studied using an anion exchange mini-bed (a short capillary column 12 mm long). The capacity factor varied according to both the amplitude and frequency of an applied alternating voltage. The variation greatly depended on the kinds of sample solutes and packing materials. A new separation mode for capillary electrochromatography using an alternating voltage, that is, alternating voltage capillary electrochromatography (AV-CEC), was proposed as an application of this phenomenon to control the retention of a sample solute. The chromatographic behavior of three organic acids (benzoic acid, phthalic acid, and salicylic acid) was studied in AV-CEC using an anion exchange column.     

Potential use of Liquid Membranes for Emergency Treatment of Drug Overdose

Several liquid membrane formulations were evaluated for the absorption of model drugs from two different donor solutions. Up to 95% of both phenobarbital and aspirin (acetylsalicylic acid) were removed from pH 2 donors and more than 85% of the former from a pH 7 donor in     

乳状液膜法提取亮氨酸

研究了亮氨酸的乳状液膜提取方法．考察了外相溶液组成、内相 Ｈ＋ 浓度、外相ｐ Ｈ 值及载体用量对提取率的影响，从而确立了各影响因素的最佳值     

Liquid chromatographic separations with mobile-phase additives: influence of pressure on coupled equilibria

On the basis of equilibrium thermodynamics, pressure can cause a shift in equilibrium for any interaction that exhibits a change in partial molar volume. This shift in equilibrium can be observed in liquid chromatography as a pressure-dependent shift in solute retention. In this paper, the impact of pressure on liquid chromatographic separations with mobile-phase additives is examined from both theoretical and experimental perspectives. The theoretical development for coupled-equilibria separations shown here is general and can be applied to any separation using mobile-phase additives. Predictions indicate that the coupled nature of these equilibria leads to pressure-induced perturbations in partitioning and complexation that can either compete with or complement one another. Using positional isomers and enantiomers as model solutes, experimental retention observations are fully consistent with these predictions, showing the diminution of individual pressure effects for competing cases and enhanced pressure effects for complementary cases. When pressure-induced changes in capacity or retention factor differ between individual solutes, changes in solute selectivity are predicted and observed. Using a C18 stationary phase with beta-cyclodextrin as the mobile-phase additive, solutes studied here exhibit changes in selectivity ranging from - 7 to + 10% for a change in average pressure of approximately 215 bar. Perhaps the most dramatic change in selectivity is observed for the separation of positional isomers where pressure-induced changes in selectivity actually reverse solute elution order.     

Self‐Assembled Metal–Phenolic Networks on Emulsions as Low‐Fouling and pH‐Responsive Particles

Interfacial self‐assembly is a powerful organizational force for fabricating functional nanomaterials, including nanocarriers, for imaging and drug delivery. Herein, the interfacial self‐assembly of pH‐responsive metal–phenolic networks (MPNs) on the liquid–liquid interface of oil‐in‐water emulsions is reported. Oleic acid emulsions of 100–250 nm in diameter are generated by ultrasonication, to which poly(ethylene glycol) (PEG)‐based polyphenolic ligands are assembled with simultaneous crosslinking by metal ions, thus forming an interfacial MPN. PEG provides a protective barrier on the emulsion phase and renders the emulsion low fouling. The MPN‐coated emulsions have a similar size and dispersity, but an enhanced stability when compared with the uncoated emulsions, and exhibit a low cell association in vitro, a blood circulation half‐life of ≈50 min in vivo, and are nontoxic to healthy mice. Furthermore, a model anticancer drug, doxorubicin, can be encapsulated within the emulsion phase at a high loading capacity (≈5 fg of doxorubicin per emulsion particle). The MPN coating imparts pH‐responsiveness to the drug‐loaded emulsions, leading to drug release at cell internalization pH and a potent cell cytotoxicity. The results highlight a straightforward strategy for the interfacial nanofabrication of pH‐responsive emulsion–MPN systems with potential use in biomedical applications.     

Continuously functioning artificial nephron system: the promise of nanotechnology

Nearly 900,000 patients worldwide have end-stage renal disease and require dialysis or kidney transplantation. Despite the availability of these forms of renal replacement therapy for nearly four decades, mortality and morbidity are high and patients often have a poor quality of life. We have developed a human nephron filter (HNF) utilizing nanotechnology that would eventually make feasible a continuously functioning, wearable or implantable artificial kidney. The device consists of two membranes operating in series within one device cartridge. The first membrane mimics the function of the glomerulus, using convective transport to generate a plasma ultrafiltrate containing all solutes approaching the molecular weight of albumin. The second membrane mimics the function of the renal tubules, selectively reclaiming designated solutes to maintain body homeostasis. No dialysis solution is used in this device. The HNF has been computer-modeled, and operating 12 hr per day, 7 days per week the HNF provides the equivalent of 30 mL/min glomerular filtration rate (compared to half that amount for conventional thrice-weekly hemodialysis). Animal studies should begin in the next 1 to 2 years, and clinical trials would then follow 1 to 2 years subsequent. The HNF system, by eliminating dialysate and utilizing a novel membrane system created through applied nanotechnology, represents a breakthrough in renal replacement therapy based on the functioning of native kidneys. The enhanced solute removal and wearable design should substantially improve patient outcomes and quality of life.     

Liquid-Crystalline Side-Chain Silastomers, Largly Modifiable Diffusion Media for the Control of Drug Delivery

Liquid-crystalline side-chain polysiloxane elastomers were synthesized in such a manner as to give thin foils that can be used as diffusion-controlling membranes or drug-loaded matrices. The structure and the properties of the silastomers can be modified by the type of polysiloxane main chain, the chain length of the dimethylpolysiloxane crosslinker and by the mesogenic group. The mesogens under investigation are 4-methoxyphenyl-4'-alkenyloxybenzoates with different lengths of the spacer. The type and the content of the mesogenic group strongly influence the permeability of the membrane. If polymers with the same type of mesogen are compared, the logarithms of the diffusion coefficients of the model drug, salicylic acid, in the LC-silastomers are linearly correlated to the mole fractions of mesogen, indicating low permeabilities at high mesogen contents. Further, the permeability depends on the state of the phases of the mesogenic domains: The diffusivity is much smaller and the activation energy much higher in the LC state at lower temperatures than in the isotropic state of the silastomer at higher temperatures; there is a distinct change in the region of phase transition. The saturation concentration of salicylic acid in the polymers increases with increasing mesogen content. Again, the type of the mesogenic group exerts an influence. Further, the solubility of the drug is higher in the LC state of the silastomer at lower temperatures than in the isotropic state. All these properties together offer multifarious possibilities to adjust the drug release to the pharmacodynamic and pharmacokinetic requirements. The importance of the state of order to the permeability of a diffusion medium and the comparability with other liquid-crystalline systems, such as biological membranes, are discussed.     

Liquid-Crystalline Side-Chain Silastomers,Largly Modifiable Diffusion Media for the Control of Drug Delivery

Abstract

Liquid-crystalline side-chain polysiloxane elastomers were synthesized in such a manner as to give thin foils that can be used as diffusion-controlling membranes or drug-loaded matrices. The structure and the properties of the silastomers can be modified by the type of polysiloxane main chain, the chain length of the dimethylpolysiloxane crosslinker and by the mesogenic group. The mesogens under investigation are 4-methoxyphenyl-4′-alkenyloxybenzoates with different lengths of the spacer. The type and the content of the mesogenic group strongly influence the permeability of the membrane. If polymers with the same type of mesogen are compared, the logarithms of the diffusion coefficients of the model drug, salicylic acid, in the LC-silastomers are linearly correlated to the mole fractions of mesogen, indicating low permeabilities at high mesogen contents. Further, the permeability depends on the state of the phases of the mesogenic domains: The diffusivity is much smaller and the activation energy much higher in the LC state at lower temperatures than in the isotropic state of the silastomer at higher temperatures; there is a distinct change in the region of phase transition. The saturation concentration of salicylic acid in the polymers increases with increasing mesogen content. Again, the type of the mesogenic group exerts an influence. Further, the solubility of the drug is higher in the LC state of the silastomer at lower temperatures than in the isotropic state. All these properties together offer multifarious possibilities to adjust the drug release to the pharmacodynamic and pharmacokinetic requirements. The importance of the state of order to the permeability of a diffusion medium and the comparability with other liquid-crystalline systems, such as biological membranes, are discussed.     

乳化液膜法脱除乙二醇中H_2S的研究

采用乳化液膜法对含H2S的乙二醇溶液进行脱硫研究.膜相由膜溶剂煤油、表面活性剂、流动载体乙二胺、膜稳定剂液体石蜡组成;内相试剂为NaOH.考察了传质时间、表面活性剂的种类及浓度、流动载体浓度、内相NaOH浓度、膜溶剂与内相试剂之比、乳化液与外相溶液之比、乙二醇溶液的初始硫含量以及传质搅拌速率对H2S脱除率的影响.试验结果表明,乳化液膜法用于含硫乙二醇溶液的脱硫是可行的,H2S脱除率可达到98%以上.     

Uremic Toxins: Removal with Different Therapies

A convenient way to classify uremic solutes is to subdivide them according to the physicochemical characteristics influencing their dialytic removal into small water‐soluble compounds (<500 Da), protein‐bound compounds, and middle molecules (>500 Da). The prototype of small water‐soluble solutes remains urea although the proof of its toxicity is scanty. Only a few other water‐soluble compounds exert toxicity (e.g., the guanidines, the purines), but most of these are characterized by an intra‐dialytic behavior, which is different from that of urea. In addition, the protein‐bound compounds and the middle molecules behave in a different way from urea, due to their protein binding and their molecular weights, respectively. Because of these specific removal patterns, it is suggested that new approaches of influencing uremic solute concentration should be explored, such as specific adsorptive systems, alternative dialytic timeframes, removal by intestinal adsorption, modification of toxin, or general metabolism by drug administration. Middle molecule removal has been improved by the introduction of large pore, high‐flux membranes, but this approach seems to have come close to its maximal removal capacity, whereas multicompartmental behavior might become an additional factor hampering attempts to decrease toxin concentration. Hence, further enhancement of uremic toxin removal should be pursued by the introduction of alternative concepts of elimination.     

Effect of polymer concentration on partitioning and molecular recognition in plasticized poly(vinyl chloride)

Mixtures of poly(vinyl chloride) (PVC) with plasticizers have been used in ion-selective electrodes for many years. The same material has proven useful in solid-phase microextraction (SPME), both with and without artificial receptors. We hypothesized that by changing the polymer concentration in plasticized PVC membranes containing artificial receptor from the standard 33 wt %, the selectivity of the extraction of barbiturates over similar molecules could be improved. Partition coefficients and receptor-substrate formation constants of a target species, phenobarbital, in membranes with various polymer concentrations were determined. Diffusion coefficients of the solute phenobarbital in receptor-free membranes were also determined. Kamlet-Taft solvatochromic properties beta and pi* were measured for the PVC/dioctyl sebacate materials. Cohesive energy densities were calculated for the same materials. Partition coefficients for phenobarbital (from aqueous solution to membrane) decrease as [PVC] increases, while the formation constants for the complex of the solute with its receptor increase. Diffusion coefficients decrease as the polymer concentration increases as well. The increase in polymer concentration brings about a decrease in hydrogen-bonding basicity and an increase in dipolarity and cohesive energy density. The values of the solvatochromic parameters determined at various compositions are highly correlated; thus, it is impossible to calculate how much each factor contributes to the changes associated with partition and complex formation. The solvatochromic "polarizability correction factor" has been determined to be 0 for PVC. In SPME experiments at 30%, 40%, and 50% (w/w) PVC, as polymer concentration increases, selectivity for barbiturate extraction over other cyclic imides becomes better in the presence of barbiturate receptor and worse without receptor.     

Physicochemical characterization and in vitro release of salicylic acid from O/W emulsions prepared with Montanov 68: effect of formulation parameters

Montanovs® are surfactants consisting of a combination of alkylpolyglucosides and long chain saturated alcohols. They are used to formulated oil in water (O/W) emulsions where they generate liquid crystals. Emulsions containing 5% Montanov 68® with 40% Lanol 1688® were prepared and salicylic acid (SA) was incorporated at different stages of the O/W emulsion preparation. This study highlights the effects of formulation parameters on the microscopic characteristics, particle size and rheologic properties of Montanov 68® O/W emulsions. Diffusion studies with these emulsions showed the influence of SA incorporation at different steps on the release kinetics. Montanov® enabled the release of SA to be controlled when it was solubilized in the internal phase. The presence of a physical barrier formed by the Montanov® at the interface between the oil and water appeared to modulate the SA passage to the external phase.     

Parametric modulation in liquid chromatography: multivariate optimization of mobile phase composition and temperature

The concept and theory of parametric modulation are presented, and the strategy is demonstrated for multivariate optimization of mobile phase composition and temperature in liquid chromatography. Because each parameter to be optimized is maintained in separate and distinct zones along the column, the solutes are able to interact independently within each environment. Under these conditions, solute retention is a simple and rigorously predictable summation of the retention in each environment. Hence, parametric modulation is more accurate and requires fewer preliminary experiments than traditional optimization methods. This approach is demonstrated by application to the separation of isomeric polynuclear aromatic hydrocarbons using a polymeric octadecylsilica stationary phase, with methanol and acetonitrile mobile phases at temperatures from 23 to 45 °C.     

Boron removal from aqueous solutions by activated carbon impregnated with salicylic acid

In this study, the removal of boric acid from aqueous solution by activated carbon impregnated with salicylic acid was studied in batch system. pH, adsorbent amount, initial boron concentration, temperature, shaking rate and salicylic acid film thickness were chosen as parameters. Boron removal efficiencies increased with increasing adsorbent amount, temperature and pH, decreasing initial boron concentration. As thickness of salicylic acid film on activated carbon becomes thin up to 0.088nm, the efficiency increased, and then, the efficiency decreased with becoming thinner than 0.088nm of salicylic acid film. Shaking rate was no effect on removal efficiency. In result, it was determined that the use of salicylic acid as an impregnant for activated carbon led to the increase of the amount of boron adsorbed. A lactone ring, being the most appropriate conformation, forms between boric acid and -COOH and -OH groups of salicylic acid.     

Theoretical and experimental studies of the effect of pressure on solute retention in liquid chromatography

Pressure is often assumed to have a negligible influence on solute retention in liquid chromatography because of the small compressibility of the mobile and stationary phases. The range of pressures commonly encountered in reversed-phase separations is considerable, however, and may give rise to significant changes in solute capacity factor. In this study, the retention of model solutes is measured directly along the chromatographic column as a function of the local pressure. The model solutes, a homologous series of derivatized fatty acids, exhibit a significant increase in capacity factor ranging from +9.3% for n-C(10) to +24.4% for n-C(20) for inlet pressures from 1500 to 5000 psi. These experimental results are compared with a thermodynamic model derived from regular solution theory. This model suggests that state effects alone are not sufficient to describe the measured change in solute retention and that variations in interaction energy with density must also be considered. By using the simple relationship of van der Waals for the interaction energy (E ∝ 1/V), the change in capacity factor with density is slightly underestimated. However, by using an extended relationship that better describes polar fluids (E ∝ 1/V(2)), good agreement is observed. Finally, the correlation of experimental results with this thermodynamic model reveals that all components in the chromatographic system, including the solute, mobile phase, and stationary phase, must be considered compressible. The results of this study have clear implications for the determination of fundamental physicochemical parameters, as well as for the everyday practice of liquid chromatography.     

Porocritical fluid extraction from liquids using near-critical fluids

In this article, Californian-based scientist Marc Sims describes a process of liquid/liquid extraction using supercritical or near critical CO₂ as the extractant solvent in a membrane separation process. Using hollow fibre or spiral wound membranes, Sims found that the transport of solutes through a membrane in a near critical fluid resulted in highly efficient separations.     

乳状液膜法处理H酸废水的实验研究

以Span-80、FSN-100为复合表面活性剂,TOA为流动载体,研究了乳状液膜处理H酸废水时TOA浓度、内相NaOH浓度、油内比Roi、外相pH、乳水比Rew及搅拌强度等因素对废水COD去除率指标的影响,分析了其内在影响因素的规律性.同时,实验结果表明乳状液膜法处理H酸废水具有较好的应用前景.