Salts Of Weak Acids Research Articles

Determination of Degradation Kinetics and Effect of Anion Exchange Resin on Dissolution of Novel Anticancer Drug Rigosertib in Acidic Conditions.

Rigosertib is a novel anticancer drug in clinical development by Onconova therapeutics, Inc. Currently, it is in pivotal phase III clinical trials for myelodysplastic syndrome (MDS) patients. Chemically, it is a sodium salt of weak acid with low solubility in lower pH solutions. In the preliminary studies, it was found that rigosertib is unstable in acidic conditions and forms multiple degradation products. In this research, drug degradation kinetics of rigosertib were studied in acidic conditions. Rigosertib follows pseudo-first-order general acid catalysis reaction. Cholestyramine, which is a strong anion exchange resin, was used to form complex with drug to improve stability and dissolution in acidic conditions. Drug complex with cholestyramine showed better dissolution profile compared to drug alone. Effect of polyethylene glycol was investigated on the release of drug from the drug resin complex. Polyethylene glycol further improved dissolution profile by improving drug solubility in acidic medium.

Study of the antibacterial activity of electro-activated solutions of salts of weak organic acids on Salmonella enterica, Staphylococcus aureus and Listeria monocytogenes.

This work assessed the antibacterial activity of electro-activated solutions of salts of weak organic acids (potassium acetate, potassium citrate and calcium lactate) on Salmonella enterica, Staphylococcus aureus and Listeria monocytogenes. This activity was compared in terms of minimal inhibitory (bactericidal) concentration to the effect of commercial acetic, citric and lactic acid at equivalent titratable acidity. Staining live/dead BacLight method was used to consider physiological state of bacteria following the evaluation of pathogenic strains during exposure to the tested solutions. The results demonstrated strong inhibitory activity of all electro-activated solutions. After 10min of exposure to electro-activated potassium acetate, a reduction of ≥6 log CFU/ml of all bacteria was observed. The electro-activated potassium citrate demonstrated the lowest minimal inhibitory concentration. Nevertheless, its inactivation power was significantly higher than that of conjugated citric acid. Although electro-activated calcium lactate was found less effective in comparison with its conjugated acid form, after 10min of contact with the tested pathogens, it induced a population reduction of 2.23, 2.97 and 5.57 log CFU/ml of S. aureus, L. monocytogenes and S. enterica, respectively.

Influence of electro-activated solutions of weak organic acid salts on microbial quality and overall appearance of blueberries during storage

The aim of this work was to study the potential of diluted electro-activated solutions of weak organic acid salts (potassium acetate, potassium citrate and calcium lactate) to extend the shelf life of blueberries during post-harvest storage. The sanitizing capacity of these solutions was studied against pathogenic bacteria Listeria monocytogenes and E. coli O157:H7 as well as phytopathogenic fungi A. alternata, F. oxysporum and B. cinerea. The results showed that a 5-min treatment of inoculated blueberries with electro-activated solutions resulted in a 4 log CFU/g reduction in Listeria monocytogenes for all solutions. For E. coli O157:H7, the electro-activated potassium acetate and potassium citrate solutions achieved a decrease of 3.5 log CFU/g after 5 min of berry washing. The most important fungus reduction was found when blueberries were washed with an electro-activated solution of potassium acetate and a NaOCl solution. After 5 min of blueberry washing with an electro-activated potassium acetate solution, a very high reduction effect was observed for A. alternata, F. oxysporum and B. cinerea, which showed survival levels of only 2.2 ± 0.16, 0.34 ± 0.15 and 0.21 ± 0.16 log CFU/g, respectively. Regarding the effect of the washing on the organoleptic quality of blueberries, the obtained results showed no negative effect on the product color or textural profile. Finally, this work suggests that washing with electro-activated solutions of weak organic acid salts can be used to enhance the shelf-life of blueberries during post-harvest storage.

Electro-activation of potassium acetate, potassium citrate and calcium lactate: impact on solution acidity, Redox potential, vibrational properties of Raman spectra and antibacterial activity on E. coli O157:H7 at ambient temperature.

AimsTo study the electro-activation of potassium acetate, potassium citrate and calcium lactate aqueous solutions and to evaluate their antimicrobial effect against E. coli O157:H7 at ambient temperature.Methods and resultsPotassium acetate, potassium citrate and calcium lactate aqueous solutions were electrically excited in the anodic compartment of a four sectional electro-activation reactor. Different properties of the electro-activated solutions were measured such as: solutions acidity (pH and titratable), Redox potential and vibrational properties by Raman spectroscopy. Moreover, the antimicrobial activity of these solutions was evaluated against E. coli O157:H7. The results showed a pH decrease from 7.07 ± 0.08, 7.53 ± 0.12 and 6.18 ± 0.1 down to 2.82 ± 0.1, 2.13 ± 0.09 and 2.26 ± 0.15, after 180 min of electro-activation of potassium acetate, potassium citrate and calcium lactate solution, respectively. These solutions were characterized by high oxidative ORP of +1076 ± 12, +958 ± 11 and +820 ± 14 mV, respectively. Raman scattering analysis of anolytes showed stretching vibrations of the hydrogen bonds with the major changes within the region of 3410–3430 cm−1. These solutions were used against E. coli O157:H7 and the results from antimicrobial assays showed high antibacterial effect with a population reduction of ≥6 log CFU/ml within 5 min of treatment.ConclusionsThis study demonstrated the effectiveness of the electro-activation to confer to aqueous solutions of organic salts of highly reactive properties that differ them from their conjugated commercial acids. The electro-activated solutions demonstrated significant antimicrobial activity against E. coli O157:H7.Significance and impact of studyThis study opens new possibilities to use electro-activated solutions of salts of weak organic acids as food preservatives to develop safe, nutritive and low heat processed foods.

Utilization of “Titanium White” Waste as Raw Material in Preparation of Poly-Ti–Fe (M-PTF) Coagulant: Changes in Characteristics During Aging Process

A poly-Ti–Fe (M-PTF) coagulant was prepared using a kind of “waste acid filter cake (WAFC)” derived from production process of “titanium white” as a raw material. The impact of aging process on the micro-characteristics of M-PTF was investigated with scanning electron microscopy (SEM), pH meter and UV spectrophotometer (UV), respectively, and coagulation performance in treating a simulated dyeing wastewater was then studied. The results indicated the following changes occurred with the increasing of aging time: the proportion of middle or high polymer part in M-PTF increased, the amount of crystalline-like structure having smooth surface morphology in the mixed netlike structure consisted of non-crystalline and crystalline-like structure increased, gradual conversion occurred from a strong acid weak base salts or acid salts to strong base weak acid salts or basic salts, and the structure and composition basically tended to be stable after aging 10 days. Removal efficiency of pollutants by M-PTF decreased with the increasing of aging time: removal of turbidity, organic matters and color reached 97, 76 and 97 %, and 61, 8 and 66 % at aging time of 1 and 26 days, respectively. Using WAFC to prepare coagulants is a feasible way, and controlling the growth of crystalline-like structure is one of the key factors to improve the stability of storage and removal efficiency of M-PTF.

HYDROLYSIS OF SALTS OF DISTINCT NATURE

The ionization theory attributes this phenomena to the interaction of water ions with the ions of dissolved salts, resulting the formation of an excess of hydrogen or hydroxyl ions. The concentration of hydrogen or hydroxyl ions in water is very low, they are in equilibrium with an immense number of unionized water molecules. When one of them is bound by the ions of the salt, the equilibrium is disturbed, causing new water molecules to ionize, which leads to accumulation an excess of quantities of the other ion, making the solution react acid or alkaline. Any salt can be obtained by neutralization of acids by bases. It is natural to assume, therefore, that solutions, at least those witch are products of complete displacement of hydrogen in acids by metals, must react neutral. However, this assumption holds only for salts of strong acids and strong bases. Salts of weak acids and strong bases, or vice versa, of strong acids and weak bases, do not react neutral when dissolved in water. The methods handbook covers the basic material on the subject ”Hydrolysis of salts of distinct nature” that may reasonably be required from Ordinary Level university standard for the trade 18.03.01 “Engineering chemistry”, in particular, when making a study in Ufa State Petroleum Technological University.

Biphasic dissolution method for quality control and assurance of drugs containing active substances in the form of weak acid salts.

Substances in the form of weak acid salts have been found to be problematic for dissolution testing. Their absorption can start only after they are turned into the form of an acid following the gastric passage although they were administered in the form of a salt. Due to poor solubility, they cannot be tested in acidic gastric environment for a biased dissolution profile. The biphasic dissolution method is promising for overcoming this obstacle. Tablets with warfarin clathrate sodium salt in two concentrations and two different particle size distributions were tested as a suitable model for finding the medium and process conditions of dissolution. The dissolution method based on the use of the upper organic layer (1-octanol) and the lower aqueous layer 0.1 mol L(-1) HCl) was found suitable and discriminatory for tablets containing active substances in the form of salts of weak acids. The method also reflects physical differences in the quality of used substances.

Solvent- and Microwave-Assisted Dehydrations of Polyols to Anhydro and Dianhydro Polyols

Carbohydrate polyol (sorbitol, mannitol, and xylitol) dehydrations by both strong and weak acid catalysts were enhanced by microwave irradiation when performed in aqueous dioxane. Reaction conditions such as the percent of water, type and concentration of acid, reaction time, and temperature were varied. Reactions with different conditions were compared by using the “combined severity” parameter. An 88% yield of the dianhydropolyol isosorbide was achieved by heating sorbitol in a microwave for only 20 min at 205 °C in 7% water/dioxane with H2SO4 as the catalyst, while heating for 1.5 h at 210 °C with the weak acid salt NaHSO4 gave 74% isosorbide. An 85% yield of 1,4-anhydroxylitol was achieved by heating xylitol in a microwave, with H2SO4 as the catalyst, for 15 min at 180 °C in 28% water/dioxane. Increasing reaction severity in the presence of the H2SO4 catalyst gave organic sulfate impurities due to solvent cleavage; in contrast, no solvent cleavage was observed with the weak acid catalyst NaHSO4.

Analysis of trace inorganic anions in weak acid salts by single pump cycling-column-switching ion chromatography.

The application of ion chromatography with the single pump cycling-column-switching technique was described for the analysis of trace inorganic anions in weak acid salts within a single run. Due to the hydrogen ions provided by an anion suppressor electrolyzing water, weak acid anions could be transformed into weak acids, existing as molecules, after passing through the suppressor. Therefore, an anion suppressor and ion-exclusion column were adopted to achieve on-line matrix elimination of weak acid anions with high concentration for the analysis of trace inorganic anions in weak acid salts. A series of standard solutions consisting of target anions of various concentrations from 0.005 to 10 mg/L were analyzed, with correlation coefficients r ≥ 0.9990. The limits of detection were in the range of 0.67 to 1.51 μg/L, based on the signal-to-noise ratio of 3 and a 25 μL injection volume. Relative standard deviations for retention time, peak area, and peak height were all less than 2.01%. A spiking study was performed with satisfactory recoveries between 90.3 and 104.4% for all anions. The chromatographic system was successfully applied to the analysis of trace inorganic anions in five weak acid salts.

Hydrolysis performance of poly-Al-Fe containing zinc (PAZF) coagulant and its removal of color and organic matters

A novel poly-Al-Fe coagulant containing zinc (PAZF) was prepared from a solid waste of galvanized-aluminum slag and its hydrolysis performance was studied. The coagulation behavior by PAZF was investigated in treating different wastewater samples compared to that by poly-aluminum-chloride (PAC). The results showed that PAZF hydrolysis could be seen as a hydrolysis process of complex salt and appeared to be characteristics of different types of salt at various concentrations. PAZF showed the nature of “strong acid and weak base salt” or “strong base and weak acid salt” at lower or higher PAZF level, respectively. For different types of wastewaters, PAZF yielded better removal of color and organic matters than PAC. For dyeing, papermaking, sugar, pharmaceutical and simulated wastewater samples, the removal of color and chemical oxygen demand (CODCr) by PAZF were up to 60.3%, 97.3%, 60%, 78.3% and 98.5%, and 32.5%, 48.1%, 41.6%, 45.4% and 82%, respectively. PAZF gave more 23%, 5%, 5%, 19% and 4%, and 8.1%, 6%, −1%, 7.2% and 18.4% than PAC in removing color and CODCr, respectively. The best pH for removing color by PAZF was different for different wastewater samples. PAZF could withstand great impact load of wastewater qualities.

Identification of key factors affecting the oral absorption of salts of lipophilic weak acids: a case example

Evaluate the ability of biorelevant media to adequately predict solubility in human gastrointestinal aspirates collected in the fasted state for the sodium salt of a highly dosed, Biopharmaceutics Classification System II (BCS II) compound with weakly acidic properties (L-870,810, pKa 7.3, HA (5-(1,1-dioxothiazinan-2-yl)-N-((4-fluorophenyl)methyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide)). Identify key luminal processes that dictate the behaviour of sodium salt of HA (NaA), after single-dose administrations of high (relatively to solubility limit) doses corresponding to 400 and 800 mg of HA in the fasted state. Aspirates from stomach and upper small intestine were collected from eight healthy fasted adults, after administration of 240 ml of water. Solubilities of NaA and HA were measured in aspirated samples and biorelevant media. Dissolution experiments of NaA granules were performed in biorelevant media. Prediction of oral pharmacokinetics was evaluated in silico using Stella software. Equilibrium solubility of NaA in fluids aspirated from the upper gastrointestinal tract is more transient than of HA. Solubility in upper gastrointestinal lumen was adequately estimated by data in biorelevant media. Supersaturation, followed by precipitation, which did not fully revert to the equilibrium solubility of HA, was observed during the dissolution of NaA granules in biorelevant media. Physiologically based pharmacokinetic modelling indicated that while intragastric processes had no significant impact on absorption kinetics, dissolution kinetics, kinetic solubility, radial transport rates and, for the 800-mg dose, precipitation kinetics in the small intestine had the greatest impact on absorption profiles. Adequate prediction of the average plasma profile, after administration of NaA, required consideration of region-dependent dissolution rates and/or solubilisation.

Uptake of Bile Acid into Calcium-Induced Alginate Gel Beads Containing <i>β</i>-Chitosan Weak Acid Salt

Recently, potential applications for β-chitosan (β-CS) have been examined. In the present study, calcium-induced alginate gel beads (Alg-Ca) containing weak acid salts of β-CS were prepared and examined with regard to their ability to adsorb bile acids in vitro. More than 70% of taurocholate dissolved in solution was taken up by Alg-Ca containing 100 mg β-CS, sim. ilar to the degree of uptake observed with Alg-Ca containing α-CS salt. The adsorption of bile acid was affected by the absolute amount of β-CS and/or the acid concentration of the preparation. A secondary bile acid, taurodeoxycholate, was also adsorbed by Alg-Ca containing weak acid salts of β-CS. Therefore, β-CS might be used to adsorb bile acids within the gastrointestinal tract in the same manner as an anion-exchange resin, and thus serve as a complementary means by which to prevent hyperlipidemia.

PH-sensitive fluorescent salicylaldehyde derivative for selective imaging of hydrogen sulfide in living cells

The salicylaldehyde derivative, 9-formyl-8-hydroxyjulolidine was developed as a fluorescent probe to detect weak acid ions. With the salicylaldehyde moiety as the chromophore, the probe exhibits pH sensitive detection of hydrogen sulfide and silicate in aqueous solution. It displays an excellent selectivity for hydrogen sulfide and silicate over other weak acid salts. Time-dependent density functional theory calculations confirmed that the fluorescence turn-on mechanism involved blocking intramolecular charge transfer. The probe detects S2− in live cells, providing a powerful method to study H2S chemistry in biological systems.

An in vitro–in silico–in vivo approach to predicting the oral pharmacokinetic profile of salts of weak acids: Case example dantrolene

The aim of this research was to characterize both the dissolution and precipitation kinetics of a model poorly water soluble drug, dantrolene, from its dissolution data, and to develop a predictive model for its oral pharmacokinetics.Physiologically based pharmacokinetic (PBPK) models were coupled with biorelevant dissolution and precipitation data to predict PK profiles of dantrolene in fasted humans. The paddle method was used to obtain the dissolution profiles of free acid form of dantrolene, dantrolene sodium, and the corresponding commercial product in biorelevant media. The Noyes–Whitney model was used to describe the dissolution kinetics, and a first-order equation was employed for estimating the precipitation kinetics from these dissolution profiles. The PBPK model was set up using STELLA® software.After an initial phase of dissolution, the concentration of dantrolene in FaSSGF and FaSSIF-V2 started to decrease again. From the overall dissolution profiles, the dissolution rate constant based on the Noyes–Whitney theory for dissolution and the first-order precipitation rate constant were calculated. The PK profiles predicted under consideration of the precipitation were close to the observed PK profile. By contrast, when only the dissolution was considered, the absorption rate was overestimated. These results indicate that PBPK modeling with dissolution and precipitation kinetics is useful for the predicting the PK profile after oral administration of dantrolene from the sodium salt and suggests a way forward for predicting PK profiles of other salts of weak acids that are poorly soluble.

Influence of variation in mobile phase pH and solute pKa with the change of organic modifier fraction on QSRRs of hydrophobicity and RP-HPLC retention of weakly acidic compounds

The variation in mobile phase pH and ionizable solute dissociation constant (pKa) with the change of organic modifier fraction in hydroorganic mobile phase has seemingly been a troublesome problem in studies and applications of reversed phase high performance liquid chromatography (RP-HPLC). Most of the early studies regarding the RP-HPLC of acid–base compounds have to measure the actual pH of the mixed mobile phase rigorously, sometimes bringing difficulties in the practices of liquid chromatographic separation. In this paper, the effect of this variation on the apparent n-octanol/water partition coefficient (Kow″) and the related quantitative structure–retention relationship (QSRR) of logKow″ vs. logkw, the logarithm of retention factor of analytes in neat aqueous mobile phases, was investigated for weakly acidic compounds. This QSRR is commonly used as a classical method for Kow measurement by RP-HPLC. The theoretical and experimental derivation revealed that the variation in mobile phase pH and solute pKa will not affect the QSRRs of acidic compounds. This conclusion is proved to be suitable for various types of ion-suppressors, i.e., strong acid (perchloric acid), weak acid (acetic acid) and buffer salt (potassium dihydrogen phosphate/phosphoric acid, PBS). The QSRRs of logKow″ vs. logkw were modeled by 11 substituted benzoic acids using different types of ion-suppressors in a binary methanol-water mobile phase to confirm our deduction. Although different types of ion-suppressor all can be used as mobile phase pH modifiers, the QSRR model obtained by using perchloric acid as the ion-suppressor was found to have the best result, and the slightly inferior QSRRs were obtained by using acetic acid or PBS as the ion-suppressor.

Solubility of potassium and sodium orthophosphates in ethylene glycol

Abstract —Solubility of potassium and sodium orthophosphates in ethylene glycol was determined. DOI: 10.1134/S1070427212050278 Phosphates of metals are used in various industries (textile, cement, glass, and ceramic) and in everyday life, including the use as components of cleaning agents, min-eral fertilizers, structural materials, and food and fodder additives. In the most widespread handbooks and separate papers [1–5] there is only information about dibasic so-dium phosphate solubility in methanol and ethanol. Data on the solubility of acid and neutral orthophosphates of alkali metals in other alcohols, glycols, cellosolves, and glycerin are absent. It is known [6–13] that the alcoholysis of weak-acid salts (carbonates, orthophosphates, sul fi des, and cyanides), of organometallic compounds, and other derivatives of alkali metals, such as acetylenides, am-ides, hydrides, nitrides, and azides, can be considered as a mode of preparation of corresponding alcoholates, whereas the alcoholysis of hydroxides is one of industrial methods of producing potassium and sodium alcoholates:

Hydrothermal synthesis of CeO2nanorods using a strong base–weak acid salt as the precipitant

Single-crystalline CeO2 nanorods of the size of about 30 nm diameter and 300 nm length were synthesised by using a strong base–weak acid salt as the precipitant, by a simple hydrothermal method without any surfactant. The structure and properties of the CeO2 nanorods were characterised by X-ray diffraction, X-ray photoelectron spectroscopy, high-resolution transmission electron microscopy, selected-area electron diffraction, UV–visible absorption and scanning electron microscopy field emission. Reaction parameters, such as the reaction temperature, the reaction time, the molar ratio of the reactants and the pH value, were investigated by a series of control experiments. The effect of the strong base–weak acid salt in the synthesis of the CeO2 nanorods was discussed.

Synthesis of one-dimensional β-Ni(OH)2 nanostructure and their application as nonenzymatic glucose sensors

One-dimensional (1D) β-Ni(OH)2 nanostructure with high surface area have been successfully synthesized via the crystallization–dissolution–recrystallization growth mechanism. The reason why the 1D beta-Ni(OH)2 nanowires can be obtained is that the intermediates α-Ni(OH)2 crystals is internal unstable state and the reaction system switched from alkalescence to acidity with increasing of reaction time. The switch from alkalescence to acidity of reaction system attribute to the hydrolysis of CF3COONa which is the strong base–weak acid salt. In the initial stage, the hydrolysis of CF3COONa provides controlled quantities of OH− ions for the formation of α-Ni(OH)2 crystals. While the OH− supplies to the precipitation of Ni(OH)2, the CF3COOH of the system increases continually. Following the incessant increase of the concentration of CF3COOH, the reaction system switched from alkalescence to acidity. The unstable state of α-Ni(OH)2 crystals derived from that CF3COO−, H2O, and NO3− were intercalated into the interlayer space of α-Ni(OH)2 crystals. The unstable state of α-Ni(OH)2 crystals make these crystals easy to redissolute into the solution and recrystallizate. The unique morphology and large BET surface areas give β-Ni(OH)2 nanowires an advantage over the β-Ni(OH)2 nanosheets in the application for nonenzymatic glucose sensor. The nonenzymatic glucose sensor based on one-dimensional β-Ni(OH)2 nanostructure exhibits an enhanced electrocatalytic property, high sensitivity, and fast amperometric sensing toward oxidation of glucose.

Hydrolytic destruction of thiamine, especially in the presence of cyanocobalamin.

Abstract The hydrolytic destruction of thiamine hydrochloride in various buffer solutions at pH 4.5 at 100° has been investigated. The rate of hydrolysis approximated to that of a first order reaction, the salts of weak organic acids acting as catalysts so that buffer salts could not retard the decomposition. It was confirmed that the hydrolytic products of thiamine affect the stability of cyanocobalamin, and that low concentrations of ferric ions can protect cyanocobalamin against the effects of thiamine breakdown products, but this occurs without appreciably affecting the stability of thiamine itself.

Potentiometric determination of sodium using a sodium ion responsive glass electrode.

Abstract A study to assess the feasibility of using a sodium ion responsive glass electrode in conjunction with a saturated calomel reference electrode to measure the sodium ion concentration of a wide range of electrolyte solutions used in clinical medicine has shown that the method is capable of giving results which are within acceptable limits. Direct measurement of solutions containing sodium chloride is possible by reference to a calibration based on the potential produced by the electrode pair as a function of pNa+ defined as -log10 sodium ion concentration. For the measurement of the sodium content of solutions of sodium salts of weak acids and mixed solutions of electrolytes and dextrose it is necessary to use a calibration carried out in a buffer system (0·5M triethanolamine + hydrochloric acid to pH 7) and to dilute the preparations with buffer before measurement. It is also necessary to buffer dextrose and sodium chloride injection before measurement due to the effect of decomposition of dextrose during sterilization causing a shift in pH which must be corrected before making a determination. The advantages of the potentiometric method over conventional flame photometric and titrimetric methods are discussed and a brief review of the literature given, to indicate the applications of specific ion electrodes.