Removal of API's (Active Pharmaceutical Ingredients) from Organic Solvents by Nanofiltration

Abstract

The removal of 5 specific active pharmaceutical ingredients (API's) with molecular weight of 189, 313, 435, 531, and 721, respectively, from toluene, methylene chloride, and methanol was studied by using solvent resistant nanofiltration. Three membranes of the StarMem series (120, 122, and 228), with cut‐off values of 200, 220, and 280 respectively, were used in the experiments. Although the rejections expected from the size difference between solutes and membrane pores are high, the results largely depended on the solvent used. For toluene, rejections were rather small, due to the low molecular weight of the solutes of interest (all API's except for the largest compound). Modelling of the rejection curve showed that the minimum molecular weight of a solute to obtain a rejection of 90% in toluene with the membranes used, is ca. 600. The application in methylene chloride was unsuccessful due to partial dissolution of the membrane top layer; other polymeric membranes such as the Solsep series might be more successful. The rejections in methanol were sufficiently high (>90%) to allow implementation: the rejection can be significantly increased by using a module design with double membrane passage and recirculation of the retentate, as was calculated from mass balances. A comparison of a (single pass) nanofiltration system with a throughput distillation unit, currently in use, showed that the energy consumption is 200 times lower in the nanofiltration system.     

Effect of impurities in the recovery of 1-(5-bromo-fur-2-il)-2-bromo-2-nitroethane using nanofiltration

The recovery of the active pharmaceutical ingredient 1-(5-bromo-fur-2-il)-2-bromo-2-nitroethane (denoted as G-1) from residual ethanol produced during the purification of G-1 was studied by using solvent resistant nanofiltration. The effect of the impurities pyridine, acetic anhydride and bromine on the process performance was studied.Four commercial nanofiltration membranes were studied in a stirred dead-end filtration module, i.e. NF 90, NF 270, Duramem 150 and BW30XLE, supplied by Evonik Industries and Filmtec (Dow). The membranes Duramem 150 and NF 90 showed the best performance, allowing a recovery of G-1 of above 60% in one stage. The separation factor of pyridine/G-1 for Duramem 150 and NF 90 was found to be higher than 2 for synthetic mixtures containing 26.75 g/L of G-1, 5.35 g/L of pyridine, 0.149 g/L of bromine and 0.105 g/L of acetic anhydride in ethanol. It was found that when using dead-end filtration, the recovery of G-1 is low when a high purity is required; both parameters cannot be optimized together. However, it is shown that with a sequence of filtrations, the recovery can be significantly improved at a given purity of G-1. These results indicate that the application of organic solvent nanofiltration for the recycling of valuable pharmaceutical compounds is feasible in realistic conditions.     

Extraction of Uranyl Ion Using 2-Thenoyltrifluoro Acetone (HTTA) in Room Temperature Ionic Liquids

The extraction of UO₂²⁺ ion was studied using six different solvent systems containing 2-thenoyltrifluoroacetone (HTTA) in room temperature ionic liquids such as [C_nmim][X] (where, n = 4, 6, or 8 and X^? = PF₆^? or NTf₂^?) from low to moderate pH solutions for the first time. The extraction kinetics studies indicated rather slow attainment of equilibrium which in some cases improved if the solutions were pre-equilibrated with the aqueous phase prior to the actual experiments. The D_U values were found to increase with increasing pH and leading to a plateau like profile at higher pH values. The D values were quite high as compared to that obtained with molecular diluents. The nature of the extracted species was ascertained by slope analysis method which suggested species of the type: UO₂(TTA)⁺_IL, UO₂(TTA)_2,IL, and UO₂(TTA)₂(HTTA)_IL in different ionic liquid based solvents. Temperature variation studies on UO₂²⁺ ion extraction were also carried out and the thermodynamic parameters were calculated which indicated high endothermicity of the reactions with large positive entropy values.     

Separation of U(VI) and Pu(IV) from Am(III) and Trivalent Lanthanides with Tri-iso-amyl Phosphate (TiAP) as the Extractant by Using an Ejector Mixer-Settler

Counter-current solvent extraction runs have been carried out to develop a suitable flow sheet for fast reactor fuel reprocessing with 1.1M Tri-iso-amyl Phosphate (TiAP)/Heavy Normal Paraffin (HNP) as the solvent by using an ejector mixer-settler facility. A spent solvent of 1.1M TiAP/HNP used for earlier runs has been employed in the present study after the regeneration. Separation of U(VI) and Pu(IV) from Am(III) and lanthanides such as La(III), Pr(III), Nd(III), Sm(III), and Eu(III) as fission product representatives with the above solvent has been investigated with an optimized flow sheet. Stage profile data generated for the extraction and strip runs for the above separation have been reported. Overall and stage-wise mass balance data for the above runs are also discussed.     

Reversible inactivation of the CG specific SssI DNA (cytosine-C5)-methyltransferase with a photocleavable protecting group

Caging of proteins by conjugation with a photocleavable group is a powerful approach for reversibly blocking enzymatic activity. Here we describe the covalent modification of the bacterial SssI DNA methyltransferase (M.SssI) with the cysteine-specific reagent 4,5-dimethoxy-2-nitrobenzylbromide (DMNBB). M.SssI contains two cysteine residues; replacement of the active-site Cys141 with Ser resulted in an approximately 100-fold loss of enzymatic activity; this indicates an important role for this residue in catalysis. However, replacement of Cys368 with Ala did not affect methyltransferase activity. Treatment of the Cys368Ala mutant enzyme with DMNBB led to an almost complete loss of activity. Irradiation of the inactivated enzyme with near-ultraviolet light (320-400 nm) restored 60 % of the catalytic activity. This indicates that caging by DMNBB can be used for the reversible inactivation of M.SssI.     

季铵盐体系金的萃取与反萃

在碱性条件下研究了十六烷基三甲基溴化铵(CTAB)微乳液体系萃取KAu(CN)2. 实验考察了水相金浓度、反萃液中卤素离子、NH4SCN及羟乙基硫醚浓度对金萃取和反萃的影响及有机相中水含量与金萃取的关系. 结果表明：CTAB/己醇/庚烷微乳液体系可将绝大部分金从水相萃取到有机相;随着萃入金的增加,有机相水含量减少. 卤素离子的反萃能力顺序为：KI>KBr>KCl;高KI浓度(>2.0 mol/L)可将有机相中绝大部分(94%)的金反萃出来. 羟乙基硫醚及NH4SCN也是金的良好反萃剂,两者混合可以降低反萃液粘度,又可以减小NH4SCN浓度,而保持较高的金反萃率.     

Extraction of Copper(II) Ions from Chloride and Sulphate Solutions Using Hydrophobic Pyridyl Ketoximes

Hydrophobic pyridyl ketoximes: 1-(2-pyridyl)tridecan-1-one oxime, 1-(3-pyridyl)tridecan-1-one oxime and 1-(4-pyridyl)tridecan-1-one oxime have been synthesized and investigated as extractants of copper(II) ions. Removal of metal ions was conducted from chloride, sulphate, and sulphate/chloride solutions. The influence of pH of aqueous solutions, copper(II), chloride, and sulphate ions and ligand concentration for extraction process were studied. Copper(II) extraction by hydrophobic 2-, 3-, and 4-pyridyl ketoximes from sulphate solutions is not possible. However, addition of chloride ions to initial sulphate media enables metal removal. The oxime of 1-(2-pyridyl)tridecane-1-one was determined as the strongest extractant of the tested oximes, but metal stripping was impossible. For the rest of the studied extractants the stripping process could be done using water or diluted mineral acid.     

Removal of Cu(II) and Zn(II) Using Lignocellulosic Fiber Derived from Citrus reticulata (Kinnow) Waste Biomass

Abstract

The biosorption of Cu(II) and Zn(II) using dried untreated and pretreated Citrus reticulata waste biomass were evaluated. The Cu(II) and Zn(II) sorption were found to be dependent on the solution pH, the biosorbent dose, the biosorbent particle size, the shaking speed, the temperature, the initial metal ions (800 mg/L), and the contact time. Twenty-eight physical and chemical pretreatments of Citrus reticulata waste biomass were evaluated for the sorption of Cu(II) and Zn(II) from aqueous solutions. The results indicated that biomass pretreated with sulphuric acid and EDTA had maximum Cu(II) and Zn(II) uptake capacity of 87.14 mg/g and 86.4 mg/g respectively. Moreover, the Langmuir isotherm model fitted well than the Freundlich model with R ² > 0.95 for both metal ions. The sorption of Cu(II) and Zn(II) occurred rapidly in the first 120 min and the equilibrium was reached in 240 min. FTIR and SEM studies were also carried out to investigate functional groups present in the biomass and the surface morphological changes of biomass.     

Removal of Zinc (II) Ions from Aqueous Solutions Using Surfactant Modified Bamboo Sawdust

The present study explores the ability of surfactant modified bamboo sawdust in removing zinc (II) ions from aqueous solutions. The modified bamboo sawdust is characterized by surface area analysis, Scanning Electron Microscope, and Fourier Transform Infrared and X-ray fluorescence analysis. Adsorption isotherm and kinetic models were used to study the adsorption characteristics of zinc (II) ions onto modified bamboo sawdust. The equilibrium adsorption isotherm data were fitted into the Langmuir and Freundlich adsorption isotherms. It was found that modified bamboo sawdust yielded maximum adsorption capacity of 111.12 mg/g at 50°C for zinc (II) ions. The kinetic data obtained at different initial concentrations were analyzed using first-order-reversible reaction, pseudo-first-order, and pseudo-second-order models. The results provide strong evidence to support the hypothesis of adsorption mechanism.     

Characterization of Adsorption Behavior of Sucrose Monolaurate on Gold Substrate Using the Quartz Crystal Microbalance (QCM)

One class of biodegradable surfactants, sucrose fatty acid esters (SEs), has attracted wide interest in the food and cosmetic industries due to their excellent biocompatibility, biodegradability and lower pH- and temperature-sensitivity. The objective of this study was to evaluate the adsorption behavior of pure sucrose monolaurate (SML) at the solid–liquid interface as a function of concentration, 0.02–0.5 % w/w, and medium pH, as these can be the pre-determinants of their performance. The quartz crystal microbalance (QCM), an effective and versatile surface adsorption tool with customizable surfaces, was used for the first time in real-time characterization of the adsorption behavior. Adsorption was fast, between 1 and 3 min, with a typical one-step monolayer adsorption mechanism occurring at most concentrations and medium pH used, thus justifying the application of the Sauerbrey equation to determine the deposited mass. The adsorption isotherm was likely Langmuirian and the SML deposition on gold was significantly higher, at and beyond 0.1 % w/w, in de-ionised water (pH 6.9) than in aqueous buffer (physiological pH 5.5) due to the interaction of water molecules with the adsorbed layer. The results from this work highlight the importance of media for studying the adsorption behaviors of SEs and serve as a reference for future investigations on different functionalized surfaces.     

Removal of Ce(IV) Ions from Aqueous Solutions Using Sawdust Coated by Electroactive Polymers

In this work, adsorption of the Ce(IV) ions onto polypyrrole (PPy) and polyaniline (PAn) conducting electroactive polymers as coated form on sawdust has been investigated. The effect of some important parameters such as initial concentration of the Ce(IV) ion adsorbent dosage, and contact time was studied. The experiments were carried out using both batch and column systems at room temperature. The equilibrium adsorption capacity of sawdust coated by polypyrrole and polyaniline for the removal of Ce(IV) ion was measured and extrapolated using linear Freundlich and Langmuir isotherms. It was found that sawdust modified by PPy and PAn improved the removal efficiency of Ce(IV) ions from aqueous solutions greatly.     

Studies on the Separation and Recovery of Uranium from Phosphoric Acid Medium Using a Synergistic Mixture of (2-Ethylhexyl)phosphonic Acid Mono 2-Ethyl Hexyl Ester (PC-88A) and Tri-n-octylphosphine Oxide (TOPO)

This paper deals with studies on the extraction of uranium(VI) from phosphoric acid medium using (2-ethylhexyl)phosphonic acid mono 2-ethylhexyl ester and tri-n-octylphosphine oxide individually as well as from their synergistic mixture. Different extraction parameters were investigated. With an increase in phosphoric acid concentration in the aqueous phase, the distribution ratio (Du) was found to decrease in all the cases. Synergism was observed when a mixture of PC-88A and TOPO was used. The synergistic mixture in the mole ratio of 4:1 (1.80 M PC-88A: 0.45 M TOPO) in xylene was found to be most suitable for uranium extraction. Among the various strip liquors used, 5% (w/v) solution of (NH₄)₂CO₃ was found to be the most suitable. Using a mixture of 1.8 M PC-88A and 0.45 M TOPO as the extractant system and 0.5 M ammonium carbonate as the stripping agent, uranium recovery was found to be better than 97% ± 3% in multiple contacts, (n = 2) from actual Davies Gray Waste while in case of wet phosphoric acid more than 52% ± 3% (n = 3) only could be recovered where n is the number of contacts.     

Removal of Copper(II) and Zinc(II) from Aqueous Solutions Using a Lignocellulosic-Based Polymeric Adsorbent Containing Amidoxime Chelating Functional Groups

In this study, the adsorption of Cu(II) and Zn(II) ions from aqueous solutions onto amidoximated polymerized banana stem (APBS) has been investigated. Infrared spectroscopy was used to confirm graft copolymer formation and amidoxime functionalization. The different variables affecting the sorption capacity such as pH of the solution, adsorption time, initial metal ion concentration, and temperature have been investigated. The optimum pH for maximum adsorption was 10.5 (99.99%) for Zn²⁺ and 6.0 (99.0%) for Cu²⁺ at an initial concentration of 10 mg L^?1. Equilibrium was achieved approximately within 3 h. The experimental kinetic data were analyzed using pseudo-first-order and pseudo-second-order kinetic models and are well fitted with pseudo- second-order kinetics. The thermodynamic activation parameters such as ΔG^o, ΔH^o, and ΔS^o were determined to predict the nature of adsorption. The temperature dependence indicates an exothermic process. The experimental isotherm data were well fitted to the Langmuir model with maximum adsorption capacities of 42.32 and 85.89 mg g^?1 for Cu(II) and Zn(II), respectively, at 20°C. The adsorption efficiency was tested using industrial effluents. Repeated adsorption/regeneration cycles show the feasibility of the APBS for the removal of Cu(II) and Zn(II) ions from water and industrial effluents.     

用198Au示踪法研究季铵盐体系萃取金

The solvent extraction of KAu(CN)2 from alkaline solution by quaternary ammonium salts (trialkylmethylammonium chloride or cetyltrimethylammonium bromide) waw investigated by means of ^198Au radioactive tracer method. Various parameters,such as the gold (I) concentration in aqueous phase,the modiffer,emulsifiation at the interface of two phases, and phase ratio used in the extraction of gold (I) were studied. The results demonstrate that almost all gold (I) in the aqueous phase was practically extracted into the organic phase. The water content in the organic phase decreased significantly with increase of gold (I) concentration using long chain alcohol as modifier,in contrast with the system with tributyl phosphate (TBP) as modifier. Emulsification at the interface of two phases decreases with an increase of modifier concentration in the organic phase or with the addition of a small amount of lysozyme into the aqueous phase. The method with ^198Au tracer can be directly used to determine the Au(I) concentration both in aqueous and organic phases, which is especially suitable for the low concentration of Au(I).     

Enhanced Removal of Cu(II) by Photocatalytic Reduction Using Maghemite PVA-Alginate Separable Beads: Kinetic and Equilibrium Studies

The feasibility of Cu(II) removal by photoreduction using maghemite polyvinylalcohol-alginate beads was investigated. Photoreduction experiments were performed to investigate the influence of initial concentration and pH on the removal of copper(II) metallic ions. The fate of Cu(II) during the photoreduction process was investigated using the X-ray photoelectron spectroscopy. It was observed that the Cu(II) removal rate was faster under sunlight than without sunlight due to the reduction process of Cu(II) to Cu(I). The photoreduction results showed that the adsorption of Cu(II) ions followed a Langmuir Hinshelwood model with the photoreduction rate constant and adsorption coefficient values of 24.1 ppm/min and 0.0098 ppm^?1, respectively.     

Effects of synthesis‐solvent composition and initiator concentration on the swelling behaviour of poly(N‐isopropylacrylamide) P(NIPAAM), poly(NIPAAM‐co‐dimethyl itaconate), and poly(NIPAAM‐co itaconic acid) gels

The effects of synthesis‐solvent composition, initiator concentration, comonomer type and monomer purity on the volume swelling ratios, and polymer‐solvent interaction parameter χ have been investigated as a function of temperature. Non‐ionic N‐isopropylacrylamide (NIPAAM) homopolymer gels, poly[NIPAAM‐co‐(dimethyl itaconate)] (P(NIPAAM‐co‐DMI)) and poly[NIPAAM‐co‐(itaconic acid)] (P(NIPAAM‐co‐IA)) gels containing hydrophobic (DMI) and hydrophilic (IA) comonomers were prepared by free radical polymerization using potassium persulfate (KPS) –N, N, N′, N′‐tetramethyl ethylene diamine (TEMED) (redox initiator) in the presence of an N, N′‐methylene bis(acrylamide) (MBAAM) cross‐linking agent. The synthesis‐solvent composition (40/60 mixture of water/methanol and water) and initiator concentration employed significantly affected the properties of the NIPAAM gels. The transition temperatures of P(NIPAAM‐co‐IA) gels synthesized in water/methanol mixture were higher than that of the gel obtained in water. Furthermore, χ values of the NIPAAM homopolymer gel prepared with higher KPS content was an increasing function of temperature, while χ values of the sample obtained with lower initiator concentration changed around a critical solubility value 0.50. The results obtained also show that the interactions between monomer and solvent molecules in the reaction media (ie composition of the pregel solution) have an important effect on the formation and properties of the network structure (ie pore sizes of the gels). © 2000 Society of Chemical Industry