Citrate Salts Research Articles

Interaction of fentanyl with various cyclodextrins in aqueous solutions.

Water-soluble fentanyl citrate salt has been used in sublingual or buccal formulations for the breakthrough pain treatment. However, fentanyl absorption through the lipid mucosal membrane may be improved by enhancing the non-ionic lipophilic fentanyl base solubility. Therefore, the interaction between cyclodextrins (CDs) and fentanyl base has been evaluated to obtain basic information for its application. Parent CDs (α-, β- and γ-CD) as well as α- and β-CD derivatives were used for solubility studies with fentanyl base. Nuclear magnetic resonance (NMR) studies were applied in a system including β-CD or glucosyl-β-CD (G1-β-CD) with fentanyl base or fentanyl citrate. (1) H- and (13) C-NMR studies and a two-dimensional rotating frame Overhauser effect spectroscopy (ROESY) study were conducted to confirm inclusion complexes formation. Parent CDs displayed BS type phase solubility diagrams; β-CD exhibited a strong interaction with fentanyl base. Hydrophilic β-CD derivatives, such as G1-β-CD, displayed AL type phase diagrams and higher solubilizing effects compared with parent CDs. ROESY study suggested that fentanyl phenyl groups were included in β-CD cavity. This study revealed that hydrophilic β-CD derivatives, such as G1-β-CD, could be useful pharmaceutical additives for oral mucosal formulations because of the improved fentanyl base solubility via inclusion complexation.

Electrochemical behavior of Cu(II), Zn(II), and Sn(II) ions in simultaneous reduction with thiosulfate ions on a molybdenum electrode

Electrochemical behavior of copper(II), zinc(II), tin(II) in joint reduction with thiosulfate ions on a molybdenum electrode from a citrate solution was studied. It was shown that use of sodium citrate salts as a complexing substance makes it possible to diminish the difference between the reduction potentials of the metals in their joint deposition. The results of an analysis of cyclic voltammetric curves were used to develop a method for electrochemical deposition of a Cu–Zn–Sn–S quaternary compound in a single stage from an aqueous solution on a molybdenum electrode at a constant potential.

Storage of washed platelets in BRS-A platelet additive solutions based on two types of clinically available bicarbonated Ringer's solutions with different electrolyte concentrations

BackgroundIn Japan, no platelet (PLT) additive solutions (PASs) are officially approved for clinical use although blood centers often receive requests for washed PLTs to reduce adverse reactions. Recently, we developed a novel PAS called BRS-A based on clinically available bicarbonated Ringer's solution (BRS), Bicanate and acid–citrate–dextrose formula A (ACD-A), which has been shown to maintain the in vitro properties of PLTs in the condition of <5% residual plasma during 7-day storage. The aim of this study was to evaluate whether another clinically available BRS, Bicarbon with different electrolyte concentrations can be used as a PAS. Study design and methodsTwo types of BRS-As were prepared by adding 25 mL of ACD-A to 500 mL of Bicanate or Bicarbon BRSs. Bicanate-based BRS-A and Bicarbon-based BRS-A contain 0.9 or 0.5 mmol/L of magnesium chloride, 95.2 or 100.1 mmol/L of sodium chloride, 4.2 or 5.1 mmol/L of trisodium citrate, and 26.6 or 23.8 mmol/L of sodium bicarbonate, respectively; the other components were identical. Apheresis PLTs stored in these solutions with less than 5% plasma for 7-day storage were compared with regard to their in vitro properties. ResultsThe pH levels of all units were above 7 throughout storage. The mean PLT volume, hypotonic shock response, glucose consumption, lactate production, swirling, and CD62P and CD42b expression were similar during 7-day storage. The bicarbonate levels in Bicarbon-based BRS-A were lower than those in Bicanate-based BRS-A. ConclusionDifferences in concentrations of electrolytes such as magnesium, sodium, citrate, and bicarbonate salts in BRS-A do not affect the in vitro properties of PLTs during 7-day storage. These results indicate that the use of another type of BRS-A based on Bicarbon as a PAS is feasible. Thus, BRS-A can be used in hospitals that do not stock Bicanate but have Bicarbon.

Non-allopathic adjuvant management of osteoarthritis by alkalinisation of the diet.

BackgroundOsteoarthritis (OA) is a chronic condition. Nonsteroidal anti-inflammatory drugs recommended for treatment have serious adverse effects. A compelling body of anecdotal evidence alerted the authors to the therapeutic potential of dietary supplementation with Multiforce® (MF) Alkaline Powder for relief of OA symptoms.AimThe aim of the study was to test the hypothesis that dietary supplementation with MF relieves clinical signs and symptoms of OA of the hands.SettingThe study was done at the MEDSAC hospital in Somerset West, Western Cape, South Africa.MethodsThe research was conducted in two stages. An open interventional study (n = 40) confirmed the notion that MF 7.5 g twice daily is likely to be an effective alternative or adjunct for relief of symptoms of OA of the hands. The main study was conducted with 100 eligible, consenting volunteers (aged 47–89 years) according to a randomised, placebo-controlled, crossover design. Study duration was 56 days, 28 days per regimen; crossover to alternate regimens took place on day 28.ResultsCompared to placebo, MF intake over 28 days was associated with significant reductions (p < 0.005) in pain, tenderness and stiffness of interphalangeal and metacarpophalangeal joints of the hand. Confirmation of systemic alkalinisation by MF, which is rich in organic anions in the form of citrate salts, was reflected by a significant and sustained increase in urine pH.ConclusionA dietary supplement, Multiforce® Alkaline Powder, containing citrate salts which are converted into bicarbonate in vivo, was efficacious and safe as sole therapeutic intervention, significantly attenuating OA-associated signs and symptoms of the hands.

Heat-Stable Dry Powder Oxytocin Formulations for Delivery by Oral Inhalation.

In this work, heat stable dry powders of oxytocin (OT) suitable for delivery by oral inhalation were prepared. The OT dry powders were prepared by spray drying using excipients chosen to promote OT stability including trehalose, isoleucine, polyvinylpyrrolidone, citrate (sodium citrate and citric acid), and zinc salts (zinc chloride and zinc citrate). Characterization by laser diffraction indicated that the OT dry powders had a median particle size of 2 μm, making them suitable for delivery by inhalation. Aerodynamic performance upon discharge from proprietary dry powder inhalers was evaluated by Andersen cascade impaction (ACI) and in an anatomically correct airway (ACA) model, and confirmed that the powders had excellent aerodynamic performance, with respirable fractions up to 77% (ACI, 30 L/min). Physicochemical characterization demonstrated that the powders were amorphous (X-ray diffraction) with high glass transition temperature (modulated differential scanning calorimetry, MDSC), suggesting the potential for stabilization of the OT in a glassy amorphous matrix. OT assay and impurity profile were conducted by reverse phase HPLC and liquid chromatography-mass spectrometry (LC-MS) after storage up to 32 weeks at 40°C/75%RH. Analysis demonstrated that OT dry powders containing a mixture of citrate and zinc salts retained more than 90% of initial assay after 32 weeks storage and showed significant reduction in dimers and trisulfide formation (up to threefold reduction compared to control).

Mesoporous carbons synthesized by direct carbonization of citrate salts for use as high-performance capacitors

A simple one-step synthesis methodology for the fabrication of mesoporous carbons with an excellent performance as supercapacitor electrodes is presented. The procedure is based on the carbonization of non-alkali organic salts such as citrate salts of iron, zinc or calcium. The carbonized products contain numerous inorganic nanoparticles (i.e. Fe, ZnO or CaO) embedded within a carbonaceous matrix. These nanoparticles act as endotemplate, which when removed, leaves a mesoporous network. The resulting carbon samples have a large specific surface area up to ∼1600m2g−1 and a porosity made up almost exclusively of mesopores. An appropriate heat-treatment of these materials with melamine allows the synthesis of N-doped carbons which have a high nitrogen content (∼8–9wt.%), a large specific surface area and retain the mesoporous structure. The mesoporous carbon samples were employed as electrode materials in supercapacitors. They exhibit specific capacitances of 200–240Fg−1 in 1M H2SO4 and 100–130Fg−1 in EMImTFSI/AN. More importantly, the carbon samples possess a good capacitance retention in both electrolytes (>50% in H2SO4 and >80% in EMImTFSI/AN at 100Ag−1) owing to their mesoporous structure which facilitates the penetration and transportation of ions.

Molecular salts and co-crystals of mirtazapine with promising physicochemical properties

Pharmaceutically suitable non-sublimating salts and molecular salts of anti-depressant drug R/S-mirtazapine with one of several dicarboxilic acids were studied. The salts/salt molecules were characterized by powder X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis and crystal structure of tartarate and oxalate molecular salt were determined by single crystal X-ray diffraction. The salts/salt molecules of mirtazapine do not show any sublimation at elevated temperature whereas sublimation of mirtazapine has been observed at ambient temperature. The aqueous solubility of the mirtazapine molecular salts was significantly improved with a maximum of citrate salt which was about 180 times more than the solubility of the parent mirtazapine at 35°C.

Room temperature seed mediated growth of gold nanoparticles: mechanistic investigations and life cycle assesment

In this study, we report the first room temperature seed-mediated synthesis of gold nanoparticles (AuNPs) in the presence of citrate and gold salt.

Densities, Sound Speed, and UV Absorption Studies of Trisodium Citrate and Tripotassium Citrate in Aqueous Solutions of 1-Hexyl-3-methylimidazolium Chloride [C6mim][Cl

Densities, ρ, and speeds of sound, u, for trisodium citrate and tripotassium citrate in (0.01 and 0.03) mol·kg–1 in aqueous solutions of 1-hexyl-3-methylimidazolium chloride ([C6mim][Cl]) over a range of temperatures T = (288.15, 293.15, 298.15, 303.15, 308.15) K have been measured at atmospheric pressure. The experimental densities are used to calculate the apparent molar volume, limiting apparent molar volumes, and transfer volumes. Experimental values of the speed of sound were used to estimate apparent molar isentropic compression, limiting apparent molar isentropic compression, and transfer parameter. The structure making or breaking ability of 1-hexyl-3-methylimidazolium chloride has been discussed in terms of the sign of (∂2Vϕ0/∂T2). The UV absorption studies have also been made in this study. The results have been discussed in terms of competing patterns of interactions prevailing in the solute and solvent, that is, citrate salt + [C6mim][Cl] + water mixtures.

Bioavailability of magnesium from inorganic and organic compounds is similar in rats fed a high phytic acid diet.

A large section of the North American population is not meeting recommended intakes for magnesium (Mg). Supplementation and consumption of Mg-fortified foods are ways to increase intake. Currently, information on Mg bioavailability from different compounds and their efficacy in improving Mg status is scant. This study compared the relative ability of inorganic and organic Mg compounds to preserve the Mg status of rats when fed at amounts insufficient to retain optimal Mg status. Male Sprague-Dawley rats (n=12/diet group) were fed one of eight test diets supplemented with phytic acid (5 g/kg diet) and low levels of Mg (155 mg elemental Mg/kg diet) from Mg oxide, Mg sulphate, Mg chloride, Mg citrate, Mg gluconate, Mg orotate, Mg malate or ethylenediaminetetraacetic acid disodium Mg salt for five weeks. Rats were also fed three control diets that did not contain added phytic acid but were supplemented with 500 (NMgO, normal), 155 (LMgO, low) or 80 (DMgO, deficient) mg of Mg per kg diet as Mg oxide. Mg concentrations in femur, serum and urine showed a graded decrease in rats fed the control diets with lower Mg. Mg concentrations did not differ (P≥0.05) between rats fed the different test diets. Addition of phytic acid to the diet did not affect the Mg status of the rats. The results indicate that any differences in the Mg bioavailability of the compounds were small and physiologically irrelevant.

Model study of the constituents of wall painting degradation patinas: The effect of the treatment with chelating agents on the solubility of the calcium salts

A model study on the application of chelating solutions on superficial calcium degradation patinas of wall paintings is presented. For this purpose the solubility of calcium sulfate, carbonate and oxalate in aqueous solutions of the Ca2+ chelators EDTA and citrate, was evaluated. Both the obtained solutions and their insoluble materials were analyzed by several analytical techniques. These studies revealed that the treatment of solid samples containing calcium sulfate and carbonate as the models of painting patinas resulted in higher solubilities of calcium sulfate and carbonate over that of oxalate. Moreover, our investigations confirmed the higher capacity of EDTA to chelate Ca2+ compared to that of citrate. All these results were interpreted and discussed on the basis of speciation models, solubility products of the salts and formation constants of the calcium complexes in solution. Finally, we report the characterization of a sodium calcium double citrate salt formed as an unexpected product in the treatment of the calcium sulfate with citrate. Overall our results suggest that the low solubility of calcium oxalate prevents its dissolution upon treatments with chelators, and that the capacity of citrate to dissolve the calcium salts is lower than that of EDTA irrespective of the duration of treatment.

Bonding in Group 1 Citrate Salts

Computational studies of &gt; 15 new crystal structures and the 10 previously-reported structures of alkali metal citrates provide insight into why the atoms are where they are. The metal-citrate bonding is predominantly ionic, with very little covalent character, which decreases as the cation size increases. Bond valence calculations indicate that most cations are crowded, and that the crowding decreases as the cation size increases. Although most oxygen atoms coordinate to the metals, a few do not, and they tend to be the least-negative oxygens. Both the citrate hydroxyl groups and water molecules tend to bridge two cations, and the carboxylate coordination is more varied. The solid state energy differences are dominated by differences in van der Waals and electrostatic energy contributions. In the Li and Na salts, the citrate anion occurs predominantly in a higher-energy "kinked" conformation, rather than the extended lowest-energy conformation observed in salts of the larger cations. Detailed conformational analysis of the citrate anions enables quantification of the conformational energy costs in these solids. Hydrogen bonding is important to the stability of these salts. The Mulliken overlap population in the hydrogen bonds provides a quantitative measure of their strength, and permits identification of long (weak) interactions which are significant in some of these compounds. Patterns in both the local environments of the hydrogen bonds and the more-extended features (graph sets) are noted. Polymorphs and sets of isostructural compounds permit more-detailed analysis of the structures and energetics in these compounds. The order of ionization of the three carboxylic acid groups is in general central/terminal/terminal, but there are two exceptions. While we have concentrated on salts containing a single alkali metal cation (and hydrogen), the structures of NaK2C6H5O7 and NaKHC6H5O7 provide an exciting window on a larger universe of mixed salts.

Synthesis and Characterization of Centhaquin and its Citrate Salt and a Comparative Evaluation of their Cardiovascular Actions

Centhaquin is a compound that produces hypotension and bradycardia in higher doses and resuscitation in lower doses. It is water insoluble, and is unsuitable for intravenous use. We prepared the citrate salt of centhaquin and evaluated its cardiovascular efficacy vs. centhaquin. Centhaquin citrate was prepared and characterized; its purity was determined by HPLC. Mean arterial pressure (MAP), heart rate (HR), pulse pressure (PP), cardiac output (CO), stroke volume (SV) and stroke work (SW) following intravenous administration of centhaquin and the citrate (0.05, 0.15 and 0.45 mg.kg(-1)) were determined in anaesthetized male Sprague-Dawley rats. Centhaquin citrate was 99.8% pure and water soluble. Centhaquin (0.05, 0.15 and 0.45 mg.kg(-1)) produced a maximal decrease in MAP of 15.6, 25.2 and 28.1%, respectively; while centhaquin citrate produced a greater (p<0.001) decrease of 35.7, 47.1 and 54.3%, respectively. The decrease in PP and HR produced by the citrate was greater than centhaquin (p<0.001). At 0.45 mg.kg(-1) centhaquin produced a maximal decrease of 20.9% (p<0.01) in CO, while centhaquin citrate produced a decrease of 42.1% (p<0.001). Reduction in SV (p<0.01) and SW (p<0.001) produced by centhaquin citrate were greater than centhaquin. Centhaquin citrate has greater cardiovascular activity compared to centhaquin.

Safety Assessment of Citric Acid, Inorganic Citrate Salts, and Alkyl Citrate Esters as Used in Cosmetics.

The CIR Expert Panel (Panel) assessed the safety of citric acid, 12 inorganic citrate salts, and 20 alkyl citrate esters as used in cosmetics, concluding that these ingredients are safe in the present practices of use and concentration. Citric acid is reported to function as a pH adjuster, chelating agent, or fragrance ingredient. Some of the salts are also reported to function as chelating agents, and a number of the citrates are reported to function as skin-conditioning agents but other functions are also reported. The Panel reviewed available animal and clinical data, but because citric acid, calcium citrate, ferric citrate, manganese citrate, potassium citrate, sodium citrate, diammonium citrate, isopropyl citrate, stearyl citrate, and triethyl citrate are generally recognized as safe direct food additives, dermal exposure was the focus for these ingredients in this cosmetic ingredient safety assessment.

Urinary calculi and infection

Infection urinary stones resulting from urease-producing bacteria are composed by struvite and/or carbonate apatite. Bacterial urease splits urea and promotes the formation of ammonia and carbon dioxide leading to urine alkalinization and formation of phosphate salts. Proteus species are urease-producers, whereas a limited number of strains of other Gram negative and positive species may produce urease. Ureaplasma urealyticum and Corynebacterium urealyticum are urease-producers that are not isolated by conventional urine cultures, but require specific tests for identification. Primary treatment requires surgical removal of stones as complete as possible. Extracorporeal and endoscopic treatments are usually preferred, while open surgery is actually limited to few selected cases. Residual stones or fragments should be treated by chemolysis via ureteral catheter or nephrostomy or administration of citrate salts in order to achieve a stone-free renal unit. Postoperatively, recurrent urinary tract infection should be treated with appropriate antibiotic treatment although long-term antibiotic prophylaxis can cause resistance. Urinary acidification has been proposed for the prophylaxis of infection stones, but long-term acidification is difficult to achieve in urine infected by urease-producing bacteria. Urease inhibitors lead to prevention and/or dissolution of stones and encrustations in patients with infection by urea-splitting bacteria, but their use is limited by their toxicity. The administration of citrate salts involves an increase of the value of nucleation pH (pHn), that is the pH value at which calcium and magnesium phosphate crystallization occurs, in a greater way than the corresponding increase in the urinary pH due to its alkalinizing effect and resulting in a reduction of the risk of struvite crystallization. In conclusion prevention of the recurrence of infection stones can be achieved by an integrated approach tailored on the single patient. Complete clearance of the stone must be achieved by primary surgical procedure and residual fragments should be extensively treated. In the case of persistent infection, conservative measures, such as acidification and urease inhibitors or citrate administration, should be adopted to minimize its effect on urinary saturation with respect to struvite.

Research on fermentation process of citric acid in solid state using sugarcane bagasse and Aspergillus Niger

Citric acid is an organic acid that has a wide range of applications in food industry and other industries. In the pharmaceutical industry, citric acid is used to produce different metal citrate salts so that these minerals can be biologically used in many medicines. For example, iron citrate made from citric acid provides iron to protect human blood, or is used to produce medicines in tablet or cream forms and cosmetics. In this research, we investigated effects of technological factors on the fermentation process of citric acid in the solid state using sugarcane bagasse and Aspergillus Niger. We conducted an experiment to determine the content of citric acid obtained in fermented liquid using HPLC. The result showed that substrate humidity, culture ratio and duration significantly influence on the fermentation process. Through the investigation of water content change in solid state from sugarcane bagasse, we indicated that during the fermentation time, a fixed amount of water to be supplemented every day to maintain the initial humidity. Based on the results, we recommend a fermentation process of citric acid using sugarcane bagasse under the following condition: substrate humidity 80%, temperature 30OC, 9-day duration, A.niger ratio 10% (v/w). The content of citric acid that can be obtained under the above condition is 12.02g/100g of sugarcane bagasse.

Antibacterial properties and mode of action of new triaryl butene citrate compounds

The aim of this study was to evaluate the antibacterial activity of newly synthesized triaryl butene analogues of tamoxifen. Several compounds were synthesized and converted to citrate salts to ensure greater solubility. Four compounds showed significant antibacterial activity at micromolar concentrations against Gram-positive and Gram-negative foodborne pathogens including Listeria monocytogenes, Listeria ivanovii, Enterococcus faecalis, Staphylococcus aureus and Escherichia coli. Two compounds at 50 μM, caused only 7.8 and 11% hemolysis. One of these as well as the remaining two caused high K+ and Na+ efflux from bacterial cells. Ultrastructural alterations were also visible using transmission electron microscopy, which revealed severe damage of the inner or outer membrane of E. coli. L. ivanovii showed swelling, corrugations and similar damage indicating a loss of cell-wall integrity. Organometallic compounds may offer interesting opportunities for the design of novel classes of antimicrobial compounds.

Laser-induced fluorescent micro-structures in silver nanoparticle based films

An optical method for the formation of micron sized line features within silver nanoparticle based films using focused laser irradiation is developed. The observed light-induced effect is a strong function of light flux producing line features with widths of less than 5μm, which can be controlled by careful selection of the focused incident beam waist. A potentially useful local feature is generated just outside the region of laser exposure; the film displays significant fluorescence emission across the visible spectrum. The source of the fluorescence is attributed to the presence of hydrated citrate salts that have been decomposed due to local heating and recrystallized as confirmed by electron microscopy and confocal fluorescence spectroscopy.

Studies on rapid multi-residue analysis of pesticides in agricultural products by LC-MS/MS

Rapid multi-residue analysis of pesticides in agricultural products was studied by using LC-MS/MS. Pesticide residues in 10 g of homogenized agricultural products were extracted with 30 mL of acetonitrile and salted out with 4 g of anhydrous magnesium sulfate and 1 g of sodium chloride in the presence of citrate salts for buffering in a disposable tube. Co-extractives were removed by use of our original triple layered column (C18/GC/PSA; 60/30/60 mg). According to the method validation guideline of the Ministry of Health, Labour and Welfare of Japan, we conducted recovery tests in 5 kinds of agricultural products (brown rice, kiwi, cabbage, sweet potato and spinach) spiked with 60 pesticides at the level of 0.01 or 0.1 μg/g. Each concentration of pesticide spiked was extracted from 2 samples per day on 5 days. Pesticides in the test solution were determined by two types of LC-MS/MS using scheduled MRM. Using this method, 58 out of 60 pesticides satisfied the guideline criteria in brown rice, 59 in kiwi, 55 in cabbage, 55 in sweet potato and 56 in spinach. This method is applicable for routine examination of pesticide residues in agricultural products.

Equilibrium Phase Behavior of Aqueous Two-Phase Systems Containing Ethylene Oxide–Propylene Oxide of Different Molecular Weight (2500, 12000) and Sodium Citrate Salt at Various Temperatures and pH

The liquid–liquid equilibrium (LLE) experimental data, including the binodal curve and the tie line of the aqueous two phase systems (ATPS) for two different molecular weights of ethylene oxide–propylene oxide copolymer (2500, 12000) and sodium citrate salt, are presented in two categories: first at different pH values 5, 7, and 8.2 at a constant temperature 25 °C and second at a constant pH of 8.2 with different temperatures of 25 °C, 30 °C, and 40 °C. It is found out that increases in the molecular weight of the polymer, pH, and temperature cause an increase of the two-phase region. Moreover, the experimental binodal data of the considered systems are successfully fitted to the Merchuk equation with significant R2 and low standard deviation.