Separation of Radiogallium from Zinc Using Membrane-Based Liquid-Liquid Extraction in Flow: Experimental and COSMO-RS Studies

ABSTRACT

A switch from batch to continuous manufacturing of gallium-68 (⁶⁸Ga) and ⁶⁸Ga-labeled pharmaceuticals can be advantageous, as it recycles isotopically-enriched zinc-68 (⁶⁸Zn), removes pre- and post-irradiation target manipulations, and provides scalability via dose-on-demand production. Herein we report efficient extraction of radiogallium (^66,67,68Ga = *Ga) from ZnCl₂/HCl solutions in batch and in flow using a membrane-based liquid-liquid separator. From 5.6 M ZnCl₂/3 M HCl, a 1/2 (v/v) diisopropyl ether (ⁱPr₂O)/trifluorotoluene (TFT) solvent extracts 76.3 ± 1.9% of *Ga and 1.9 ± 1.6% of Zn in flow using a single pass through. From 1 M ZnCl₂/6 M HCl, a 1/2 (v/v) n-butyl methyl ether (n-BuOMe)/TFT solvent extracts 95.7 ± 2.0% of *Ga and 0.005 ± 0.003% of Zn in flow. TFT plays a key role in controlling the interfacial tension between the aqueous and the organic phases, ensuring clean membrane-based separation. The process did not extract Cu, Mn, and Co but did extract Fe. Using HGaCl₄ and ZnCl₂ as the extractable species, the COSMO-RS theory predicts the solvation-driven extraction of Ga and Zn with a mean unsigned error of prediction of 4.0% and 3.4% respectively.     

Applications of choline amino acid ionic liquid in extraction and separation of flavonoids and pectin from ponkan peels

Choline leucine ionic liquid solution was chosen to simultaneously extract flavonoids and pectin from ponkan peels, which were subsequently isolated by the corresponding K₃PO₄-based aqueous biphasic systems (ABS). Under optimized conditions of 54% solution for 100 min extraction at liquid–solid ratio 17, the predicted yields of flavonoids and pectin achieved 1.33% and 13.42%, respectively, the flavonoids determined directly after extraction and the pectin after ABS purification, with the two corresponding measured yields of 1.26% ± 0.04% and 12.85% ± 0.51%. Under optimal extraction, crude flavonoids contained maximal total flavonoid content of about 20% ± 1% after purification of the ABS involving 25% K₃PO₄ and dilution precipitation. What was directly isolated from K₃PO₄-rich phase was presumed to be a modified pectin.     

Improved recovery of B‐phycoerythrin produced by the red microalga Porphyridium cruentum

A simplified process for the primary recovery and purification of B‐phycoerythrin (BPE) from Porphyridium cruentum exploiting aqueous two‐phase systems (ATPS) and isoelectric precipitation was developed in order to reduce the number of unit operations and benefit from increased purity and yield of the protein product. Evaluation of the partitioning behaviour of BPE in polyethylene glycol (PEG)/sulphate, PEG/dextran and PEG/phosphate ATPS was carried out to determine under what conditions the BPE and contaminants concentrated into opposite phases. An additional stage of isoelectric precipitation at pH 4.0 after cell disruption resulted in an increase in purity of the target protein from the BPE crude extract and enhanced the performance of the subsequent ATPS. PEG1000/phosphate ATPS proved to be suitable after isoelectric precipitation for the recovery of highly purified (defined as absorbance ratio A_{545 nm}/A_{280 nm} > 4.0) BPE with a potential commercial value as high as US$ 50/mg. An ATPS extraction stage comprising 29.5% (w/w) PEG1000, 9.0% (w/w) phosphate, a volume ratio (V_r) equal to 1.0, a system pH of 7.0 and loaded with 40% (w/w) of the BPE extract generated by precipitation allowed BPE recovery with a purity of 4.1±0.2 and an overall product yield of 72% (w/w). The purity of BPE from the crude extract increased 5.9‐fold after isoelectric precipitation and ATPS. The results reported herein demonstrate the benefits of the practical application of isoelectric precipitation together with ATPS for the recovery and purification of BPE produced by P. cruentum as a first step in the development of a commercial purification process. Copyright © 2006 Society of Chemical Industry     

Natural Pigments Extraction from Basella rubra L. Fruits by Ultrasound-Assisted Extraction Combined with Box-Behnken Response Surface Design

In this study, natural pigments from Basella rubra L. were extracted by ultrasound-assisted extraction (UAE) technique using three levels, four factors (extraction temperature, ultrasonic power, extraction time and solid-liquid (SL) ratio) Box-Behnken response surface design. The optimal condition was found to be: extraction temperature of 54°C, ultrasonic power of 94 W, extraction time of 32 min and SL ratio of 1:17 g/mL respectively. Under this optimal condition, the experimental yield of (betacyanin of 1.42 ± 0.001 and betaxanthin of 5.35 ± 0.13 mg/g) pigments were well correlated with predicted values (betacyanin was 1.43 mg/g and betaxanthin was 5.37 mg/g).     

Extraction of Astaxanthin from Shrimp Waste using Response Surface Methodology and a New Hybrid Organic-Inorganic Monolith

A 17-run Box-Behnken design (BBD) with three factors was used to improve the conditions for extracting astaxanthin from shrimp waste. The astaxanthin level was determined by high performance liquid chromatography (HPLC) using a C₁₈ column and a UV detector at 476 nm. The mean extraction yield of astaxanthin at the improved conditions (extraction time 1.4 h, extraction temperature 72.4°C, and liquid-solid ratio 27.3) was 98.7 ± 2.6 µg g^?1. A solid-phase extraction (SPE)-HPLC method was developed with a new hybrid organic-inorganic hybrid monolith for further purification of astaxanthin from shrimp waste. The SPE recoveries were ranging from 81.3 ± 2.4% to 86.5 ± 3.3%, and the intra-day and inter-day relative standard deviations (RSDs) of the proposed method were less than 4.3 ± 0.5% and 4.8 ± 0.2%, respectively. BBD increased the extraction efficiency and shortened extraction times significantly. SPE-HPLC with hybrid monolith showed good selectivity and purified astaxanthin from shrimp waste.     

Kariya (Hildegardia barteri) seed oil extraction: comparative evaluation of solvents,modeling, and optimization techniques

In this work, the effects of solid/solvent ratio (0.10–0.25?g/ml), extraction time (3–8?h), and solvent type (n-hexane, ethyl acetate, and acetone) together with their shared interactions on Kariya seed oil (KSO) yield were investigated. The oil extraction process was modeled via response surface methodology (RSM), artificial neural network (ANN) and adaptive neuro-fuzzy inference system (ANFIS) while the optimization of the three input variables essential to the oil extraction process was carried out by genetic algorithm (GA) and RSM methods. The low mean relative percent deviation (MRPD) of 0.94–4.69% and high coefficient of determination (R²) > 0.98 for the models developed demonstrate that they describe the solvent extraction process with high accuracy in this order: ANFIS, ANN, and RSM. The best operating condition (solid/solvent ratio of 0.1?g/ml, extraction time of 8?h, and acetone as solvent of extraction) that gave the highest KSO yield (32.52?wt.%) was obtained using GA-ANFIS and GA-ANN. Solvent extraction efficiency evaluation showed that ethyl acetate, n-hexane, and acetone gave maximum experimental oil yields of 19.20?±?0.28, 25.11?±?0.01, and 32.33?±?0.04?wt.%, respectively. Properties of the KSO varied based on the type of solvent used. The results of this work showed that KSO could function as raw material in both food and chemical industries.     

n-3 Polyunsaturated Fatty Acids and Atopy in Korean Preschoolers

Atopy is a growing problem for Korean children. Since eicosapentaenoic acid is a precursor of less active inflammatory eicosanoids, n-3 polyunsaturated fatty acids (PUFA) may have a protective effect on atopy. This study was undertaken to determine whether n-3 PUFA in red blood cells (RBC) is lower in atopic than in non-atopic preschoolers. Three hundred and eight Korean children aged 4–6 years were enrolled. Total RBC fatty acid composition was measured by gas chromatography. The prevalence of atopic dermatitis, allergic rhinitis, or asthma was 29%. Total RBC n-3 PUFA were lower in preschoolers with atopy than controls (9.8 ± 1.2 vs. 11.4 ± 1.6%; P < 0.05), while n-6 PUFA (33.0 ± 1.4 vs. 32.2 ± 1.0%; P < 0.05) and n-6/n-3 PUFA ratio (3.4 ± 0.6 vs. 2.8 ± 0.5; P < 0.05) were greater. The following factors were also associated with an increase in atopy: higher saturated fatty acids (39.6 ± 1.4 vs. 40.6 ± 1.9; P < 0.05) and arachidonic acid (15.3 ± 1.6 vs. 16.0 ± 2.9; P < 0.05), and lower total PUFA (43.8 ± 0.7 vs. 42.8 ± 1.4; P < 0.05) and omega-3 index (EPA + DHA; 9.1 ± 0.8 vs. 7.8 ± 0.5; P < 0.05) in RBC. Maternal history of atopy was a significant (P < 0.05) risk factor, while lactation was not. The results suggest that a reduced content of n-3 PUFA in the RBC membrane could play a role in early children atopy.     

The effects of solvent polarity and pKa on the absorption of solvents into poly(glutaric acid‐glycerol) films

In this study, solvent absorption into the matrices of poly(glutaric acid‐glycerol) films has been evaluated. It was determined that the combined effects of polarity and the size and shape of the solvent molecule, rather than pKa, have the most significant influence on absorption into the films. Polar aprotic solvents (with solvent polarity index values >4) such as 1,4‐dioxane (absorbed 163.8% ± 0.3% [w/w] of the original weight of the polymer), pyridine (200.4% ± 3.5%), and dimethyl sulfoxide (186.0% ± 11.4%) were among the highest absorbed solvents into the polymer matrix. Solvents with polarity index values ≤4.0 were absorbed poorly (≤5.3% ± 1.5%). The polymer films only absorbed ≤26.5% ± 2.1% of their weight of most protic solvents (water and mono‐alcohols) but absorbed 72.6% ± 6.5% of ethylene glycol, a diol. The only high absorbing polar protic solvent was acetic acid (131% ± 13.1%). Except for chloroform, ethyl acetate, and ethanol, all of the solvents examined displayed small increases in absorption (7.8%, on average) when the films were desorbed and used again to absorb solvent. Erosion of the films ranged from 0.0% ± 0.0% to 22.0% ± 3.2% after 2–10 h absorption cycles. Miscible (7.7% ± 2.3% to 15.1% ± 2.2%) and immiscible (12.3% ± 6.4% to 80.0% ± 1.9%) solvents were preferentially absorbed from aqueous solutions. However, up to approximately 5% of those absorption values could be from water absorption. © 2014 Wiley Periodicals, Inc.^? J. Appl. Polym. Sci. 2014 , 131, 40434.     

Optimization of ultrasound-assisted extraction of bioactive compounds from B. forficata subsp. Pruinosa

Extracts containing bioactive compounds were obtained from Bauhinia forficata leaves by ultrasound-assisted extraction (UAE) with three different solvents (n-hexane, ethyl acetate, and ethanol) and were compared with those obtained by a conventional method (maceration). Box-Behnken experimental design was applied to examine and optimize the effect of the extraction temperature (40°C-60°C), power (20%-80%), and sample to solvent ratio (1:10 to 1:20 (w/v)) on the total phenolic content (TPC), total flavonoid content (TFC), and the ferric reducing antioxidant power (FRAP) of B. forficata leaf extracts. This experimental design generated second-order polynomial models, which accurately describe the experimental data, allowing the prediction of optimal conditions for the investigated responses. Optimal extraction was achieved under the following conditions: 80% power, temperature of 41°C, and a 1:20 sample to solvent ratio. Under these conditions, the experimental yield was 8.33 ± 0.32%, total phenolic content was 59.47 ± 0.71 mg GAE · g_extract⁻¹, total flavonoid content was 62.30 ± 3.38 mg QE · g_extract⁻¹, and the ferric reducing antioxidant power was 726.7 ± 15.7 μmol Fe(II)EQ · g_extract⁻¹, which were close to the predicted values, which validated the models. The major compounds found in B. forficata extracts were tocopherols, phytol, heneicosane, and β-Sitosterol.     

Large-Scale Preparative Isolation of Rosavin from Rhodiola rosea via Ion Liquids MAE and Subsequent Flash Adsorption Chromatography

Rosavin was a major active compound from Rhodiola rosea. It is known that it possesses stimulant, antidepressant, and anticancer properties. In the present study, a two-step flash column chromatography has been developed for the large-scale preparative separation and purification of rosavin from the extracts of Rhodiola rosea, which were obtained by microwave assisted extraction (MAE) using ion liquids (ILs) as extraction solvent under the optimized conditions (microwave power 1200 W, extraction time 6 min, solid-liquid ratio 1:20, microwave temperature 120°C) resulting from the analysis of the D-optimal design. In the first separation, the Rhodiola rosea extract was loaded into polyamide and HPD-200 macroporous resin flash columns in series for efficient enrichment of rosavin. In the second one, the rosavin-rich crude sample after the serial column chromatography was subjected to final purification by silica gel flash chromatography. After the two-step separation, 529.1 mg of rosavin was obtained at a purity of 98.2% and a recovery of 60.6%. The separation process can provide a new method for large-scale separation and purification of rosavin for its pharmaceutical and practical use.     

Optimization of Microwave‐Assisted Extraction of Flavonoid from Radix Astragali using Response Surface Methodology

Abstract

Response surface methodology (RSM) was applied to predict optimum conditions for microwave‐assisted extraction (MAE) of flavonoid from Radix Astragali. A central composite design was used to monitor the effect of temperature, extraction time, solvent‐to‐material ratio, and the ethanol concentration on yield of total flavanoid (TFA). Optimum extraction conditions were predicted as 108.2°C, 26.7 min, 23.1 ml/g solvent‐to‐material ratio and 86.2% ethanol. The maximum yield 1.234±0.031 mg/g was close to the yield of Soxhlet and higher than that of ultrasound assisted extraction and heat reflux extraction. MAE was an effective alternative to conventional extraction methods.     

Integrated process of extraction and purification of betanin from Opuntia ficus-indica using aqueous two-phase systems based on THF and sodium salts

This research present an integrated process for the extraction and purification of betanin from fruit of Opuntia ficus-indica. The extraction process was evaluated using different solvents (water, acetonitrile, ethanol and tetrahydrofuran), and then integrated into the purification process using aqueous two-phase systems (ATPS). The optimum conditions for extraction was with THF and the purification conditions determined to be 43 wt% of THF and 6 wt% of sodium citrate buffer (pH 5.5) at 25°C. A purification factor of 13.7 ± 0.5 fold, with a partition coefficient of betanin for salt-rich phase and the antioxidant capacity was increased ≈ 65%.     

Chitin Extraction from Black Tiger Shrimp (Penaeus monodon) Waste using Organic Acids

Abstract

In chitin extraction from black tiger shrimp shell waste, HCl is the commonly used decalcifying agent. However, it is considered a harsh chemical. An alternate was found by using organic acids. Conditions for deproteinization were: 1 M NaOH at 95°C for 6 h and solid‐to‐solvent ratio of 1∶15 (w/v). Demineralization involved treatment with 0.25 M HCl at ambient temperature for 30 min with agitation. The optimal solid‐to‐acid ratio was 1∶30 (w/v) and this led to 86.5±1.2% purification of chitin. With the same conditions, the optimal ratio of mixed acids (0.25 M HCOOH and 0.25 M C₆H₈O₇ at 1∶2 (v/v)) was 1∶28 (w/v) with chitin purification of 88.1±1.8%.     

Squalene from Fish Livers Extracted by Ultrasound-Assisted Direct In Situ Saponification: Purification and Molecular Characteristics

An ultrasound-assisted direct in situ saponification (U-DS) process was developed to extract unsaponifiable matter (rich in squalene) from the livers of four fish species, sea bass, skipjack tuna, gray bamboo shark, and spot-tail shark. The conventional solvent extraction method was used for comparison. Box–Behnken experimental design (BBD) was adopted to optimize the independent variables including the biomass/methanol ratio (1:3 to 1:9 w/v), 50% KOH volume (1–12 mL), and sonication time (0–30 min) over the unsaponifiable yield. With the conventional process, the yield of squalene was 0.10 ± 0.02 to 5.52 ± 0.06 g (100 g)⁻¹, whereas the U-DS process rendered the yield of 0.13 ± 0.03 to 6.86 ± 0.05 g (100 g)⁻¹, depending on the fish species. After extraction, squalene was further concentrated (purity ≥60%) from all fish species via fractional crystallization (yield of squalene concentrate ranged from 48.35% to 74.49%) and purified using a silica gel column with a maximum recovery up to 98%. For all the fractions, components were examined using thin layer chromatography (TLC). Squalene was qualitatively and quantitatively analyzed using reversed-phase high-performance liquid chromatography (RP-HPLC). Entire extraction processes yielded squalene with a purity of ≥94%. Fourier transform infrared (FTIR) analysis confirmed the native structure of squalene with six nonconjugated bonds, suggesting no degradation of squalene taken place during the U-DS process. Thus, the U-DS process along with fractionation and purification could be used for recovering the squalene from fish livers.     

Comparison of extraction methods for determining tocopherols in soybeans

We evaluated the usefulness of saponification, direct solvent extraction, and Soxhlet extraction as extraction methods to determine the amounts of tocopherols in soybeans. Soxhlet extraction yielded the highest analytical values for each tocopherol homolog and was the best method for quantifying tocopherols in soybeans. Coupling of simple Soxhlet extraction with HPLC provided a highly reproducible procedure to quantify tocopherols in soybeans. The percent mean recovery ± standard deviation (n = 5) was 103.2 ± 1.21, 109.8 ± 4.18, 93.8 ± 1.12, and 106.9 ± 1.54% for α‐, β‐, γ‐, and δ‐tocopherol, respectively. The linearity test for quantification was carried out over the ranges of 0.4–10.0, 0.2–4.0, 2.0–16.0, and 0.4–10.0 µg/mL for α‐, β‐, γ‐, and δ‐tocopherol, respectively. Regression analysis showed an excellent linear relationship (R² >0.998), and the results of the validation parameters were generally reliable and satisfactory.     

Increasing Stearidonic Acid (SDA) in Modified Soybean Oil by Lipase-Mediated Acidolysis

The objective of this work was to synthesize a structured lipid (SL) enriched in stearidonic acid (SDA, C18:4 ω-3), from modified soybean oil (MSO) originally containing ~25% SDA. Low temperature crystallization (LTC) of MSO triacylglycerols (TAG) and free fatty acids (FFA) was performed. The TAG and FFA crystallization products (LTC-TAG and LTC-FFA, respectively) had SDA contents of 48.72 and 60.78%, respectively. Enzymatic acidolysis between MSO and LTC-FFA was studied utilizing Novozym 435 and Lipozyme TL IM as biocatalysts. Substrate molar ratio, incubation time, solvent, and enzyme load were explored. Equilibrium was reached at 96 and 48 h for Novozym 435 and Lipozyme TL IM-catalyzed reactions, respectively. The best conditions from these studies were also applied to the acidolysis of LTC-TAG and LTC-FFA. Utilizing Lipozyme TL IM and solvent free conditions, SLs with SDA contents of 37.61 ± 1.00% (20.86 ± 6.48% at sn-2 position) and 53.46 ± 1.85% SDA (36.37 ± 3.14% at sn-2 position) were obtained from the acidolysis reaction between MSO and LTC-FFA, and LTC-TAG and LTC-FFA, respectively. Compared to the original SDA content of MSO, this process leads to a 52 and 116% increase in SDA content, respectively.     

Lipid composition of eggs of an oviparous lizard (Bassiana duperreyi)

Lipid analysis was performed on freshly ovulated eggs (n=5) of the oviparous lizard Bassiana duperreyi. The fresh weight of the whole egg contents was 132.0±4.3 mg (mean+SF) of which lipid constituted 21.9+1.1% (w/w). Iriacylglycerol formed an exceptionally high proportion (85.4+ 0.5%, w/w) of the total lipid, whereas phospholipid, free cholesterol, cholesteryl ester, and free fatty acid, respectively, contributed 11.2±0.3, 1.4±0.1,1.3±0.1, and 0.6±0.1% of the total lipid mass. Linoleic and α-linolenic acids were the major polyunsaturates of the triacylglycerol fraction, respectively, forming 16.3±0.1 and 8.3±0.1% (w/w) of the fatty acids. Linoleic acid was the major fatty acid (29.0±0.1%) of the total phospholipid, which also contained substantial amounts of arachidonic (6.4±0.1%) and eicosapentaenoc (3.0±0.1%) acids, but a relatively low proportion (1.6±0.1%) of docosahexaenoic acid. Phosphatidylcholine formed the major phospholipid class (73.8±2.3% w/w of total phospholipid) and was enriched in linodeic acid, whereas phosphatidylethanolamine, which formed 20.4±1.9% (w/w) of total phospholipid, contained higher proportions of arachidonic and docosahexaenoic acids.     

Solvent-assisted extraction of oil from papaya (Carica papaya L.) seeds: evaluation of its physiochemical properties and fatty-acid composition

ABSTRACT

The present work reports the solvent-assisted extraction of oil from papaya (Carica papaya L.) seeds. Various operating parameters such as solid solvent ratio, temperature and time on oil yield, and its effects have been investigated using response surface methodology. The experimental oil yield (20.30 ± 0.03%) at optimal condition was well agreed with the predicted value. The compositions from GC-FID results showed saturated fatty acid (20.94%), monounsaturated fatty acid (73.12%), and polyunsaturated fatty acid (4.96%). It was also found that the solvent-assisted extraction is a simple and effective method for extraction of oil from papaya seeds.     

Carrier Facilitated Transport of Europium(III) Across Supported Liquid Membranes Containing N,N,N′,N′-tetra-2-ethylhexyl-3-oxapentane-diamide (T2EHDGA) as the Extractant

Studies on the solvent extraction and pertraction behavior of europium(III) was carried out from acidic feed solutions using N,N,N′,N′-tetra-2-ethylhexyl-3-oxapentane-diamide (T2EHDGA) in n-dodecane as the solvent. The nature of the extracted species from the solvent extraction studies conformed to Eu(NO₃)₃ · 3T2EHDGA which is in variance with the analogous Eu(III) – TODGA (linear homolog of T2EHDGA) extraction system. The transport behavior of Eu(III) was investigated from a feed containing 3.0 M HNO₃ into a receiver phase containing 0.01 M HNO₃ across a PTFE flat sheet supported liquid membrane (SLM) containing 0.2 M T2EHDGA in n-dodecane as the carrier solvent and 30% iso-decanol as the phase modifier. Effects of feed acidity, carrier extractant concentration, membrane pore size, and Eu concentration in the feed on the transport rates of Eu(III) were also investigated. Membrane diffusion coefficient (D _o) for the pertracted species was calculated using the Wilke-Chang equation as 4.25 × 10^?6 cm² · s^?1. The influence of Eu concentration on the flux was also investigated. The role of temperature on the transport rates was investigated and the thermodynamic parameters were calculated.     

Effect of grass vs. concentrate feeding on the fatty acid profile of different fat depots in lambs

The aim of this study was to produce high‐quality meat from lambs under different feeding conditions, as measured by the accumulation of n‐3 fatty acids and conjugated linoleic acids (CLA) in muscle and subcutaneous fat. In total, 13 male crossbred lambs (Black Head×Gotland), each at 24 kg live weight, were divided into two feeding groups. Lambs were kept either on pasture (pasture grazing, n = 6) or in the stable (concentrate feeding, n = 7). The linolenic acid (C18:3n‐3) contained in the grass was absorbed and deposited into the different lipid classes of muscle and subcutaneous fat. The proportion of total n‐3 fatty acids in the different lipids of grazing lambs was significantly (p = 0.05) higher compared to that in concentrate‐fed lambs. The n‐6/n‐3 ratio (mean ± SEM) in muscle of grazing lambs was 1.2 ± 0.09 in contrast to 2.3 ± 0.09 (p = 0.05) of the animals kept in the stable. In subcutaneous fat, this ratio was 0.9 ± 0.2 in lambs kept on pasture versus 3.5 ± 0.2 (p = 0.05) after indoor keeping. The relative concentration of C18:1trans‐11 in total muscle lipids, phospholipids, triacylglycerols and subcutaneous fat was significantly increased by grass feeding compared to concentrate feeding. Significant influences of feeding were shown for saturated fatty acids. In concentrate‐fed lambs, a lower content of saturated fatty acids was detected. The proportion of CLAcis‐9,trans‐11 (1.9 ± 0.2% vs. 1.1 ± 0.1% in muscle, 2.5 ± 0.2% vs. 1.4 ± 0.2% in subcutaneous fat, 0.7 ± 0.04% vs. 0.4 ± 0.04% in phospholipids) in lambs was significantly (p = 0.05) higher after grazing than after concentrate feeding, respectively.