Degradation kinetics of fluvoxamine in buffer solutions: In silico ADMET profiling and identification of degradation products by LC-MS/ESI

The kinetics of hydrolysis of fluvoxamine maleate (FLV) has been investigated over the pH range 1.0–12.0 at 40, 60 and 80 °C. FLV degradation follows pseudo-first-order kinetics which is consistent with the kinetics of drugs that are not readily dissolved in aqueous medium. The hydrolytic degradation rate constant (k_obs) range from 0.92 (pH 6.0) to 13.8 × 10⁻⁴ min⁻¹ (pH 1.0). The k_obs represents the sum of six different degradation rate constants; the k_H has been found to be higher than k_OH. The FLV exhibits a typical rate- pH profile with a flat bottom over the pH range 3.0–6.0 which indicates its maximum stability at pH 6.0. Ten FLV degradants have been predicted by Zeneth software and among them four degradation products (D1, D2, D3 and D4) have been identified in degraded samples. The in-silico pharmacokinetics and toxicity of degradation products have been determined using Swiss ADME and admetSAR software. The toxicity profile reveals that D2 is both AMES toxic and carcinogenic while the rest of the products are non-AMES toxic and non-carcinogenic. All of the degradation products are high in causing fish toxicity thus their presence in pharmaceutical waste is alarming for environmental safety.     

In-vivo and in-vitro testing to assess the bioaccessibility and the bioavailability of arsenic, selenium and mercury species in food samples

In-vivo and in-vitro gastrointestinal (GI) extractions, also known as oral bioaccessibility and bioavailability, are important approaches to assess chemical risk to humans. We give an overview of in-vivo and in-vitro bioaccessibility and bioavailability assays for testing arsenic, selenium and mercury (As, Se and Hg) species from food samples. We critically evaluate the parameters affecting in-vivo and in-vitro processes. In addition, we consider the effect of cooking food on bioaccessibility and bioavailability, and stability and transformation, of species during in-vivo or in-vitro processes. The bioaccessibility and bioavailability of As, Se and Hg species are affected by the sample matrix, cooking food and the experimental conditions applied (gastric and intestinal pH, incubation temperature and residence time). Regarding species degradation and transformation during in-vitro procedures, good stability has been observed for most As species, except for certain arsenosugars. Important transformations during in-vitro processes have been reported for Se species [e.g., conversion of γ-glu-Se-MeSeCys to Se-MeSeCys, and organic Se species (MeSeCys, SeCys2 and SeMet) degradation to inorganic Se]. Finally, we summarize speciation and detection conditions for As, Se and Hg speciation, and quality control to assure reliable measurements.     

Interaction forces between α-alumina fibres in aqueous electrolyte measured with an atomic force microscope

The surface charging properties of polycrystalline α-alumina fibres in aqueous electrolyte solutions have been investigated by direct force and streaming potential measurements. The presence of both Al and Si on the surface of the fibres resulted in a chemically heterogeneous surface. The heterogeneous distribution of Si resulted in large attractive forces between the fibres at moderate to low pH values and a pzc/iep at a pH value of approximately 5.5. The origin of this force was electrostatic in nature as the force profiles were well described by the DLVO theory of colloid stability. The agreement between the direct force and streaming potential measurements was good both in terms of the magnitude of the potentials and the position of the pzc/iep. By acid washing the fibres the chemical heterogeneity of the surface was reduced and the attractive force profiles at lower pH values were not observed. Instead repulsive forces were observed which were well described by DLVO theory at all separation distances greater than 8 nm. At smaller separation distances an additional repulsive force was measured which was attributed to the presence of a Al(OH)₃ like layer on the surface of the alumina. The acid washing treatment also resulted in a shift in the pH at which the pzc/iep occurred to a value of 6.5, presumably due to a lower surface silica concentration.     

Preparation and characterization of new hydrogels based on hyaluronic acid and α,β-polyaspartylhydrazide

Hyaluronic acid (HA) has been crosslinked with α,β-polyaspartylhydrazide (PAHy). The crosslinking reaction has been performed in acidic medium in the presence of various amounts of N-ethyl-N′-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC). All obtained samples have been characterized by FT-IR analysis and swelling measurements in double distilled water that have confirmed the occurrence of a chemical linkage between two polymers and the affinity towards aqueous medium of HA-PAHy networks, respectively.In vitro degradation assays have been performed in simulated physiological conditions as well as in the presence of hyaluronidase. Experimental data evidenced that HA-PAHy samples undergo a poor chemical and a reduced enzymatic degradation unlike native HA.     

Biosensors based on a light-addressable potentiometric sensor (LAPS) for analysis in both aqueous solutions and organic solvents

Characteristics of a light-addressable potentiometric sensor (LAPS) based on silicon with Ta₂O₅ dielectric are reported. The pH sensitivity obtained is 45 mV/pH unit in the pH range from 4.01 to 7.5 (for measurements conducted in citrate buffer solutions) and 55 mV/pH unit over the pH range from 7.5 to 8.9 (for measurements conducted in Tris-HCl buffer solutions). The kinetic characteristics (K _m ³ V _m ⁵ pH-profile) of different enzymes, i.e., glucose oxidase, α-chymotrypsin, butyrylcholin esterase, and urease, have been measured under homogeneous conditions. The values of the Michaelis constant obtained are very close to analogous data described in the literature. Biosensors were prepared by immobilization of the enzymes on a pH-sensitive matrix. Two methods of immobilization were used: incorporation in to a hydrophilic matrix of bovine serum albumin (BSA) and incorporation into a hydrophobic matrix of modified polyethylenimine (PEl). It is demonstrated that LAPS can be used for recording the enzymatic reactions in organic media (mixture of the solvents).     

Thermal and fire stability of cotton fabrics coated with hybrid phosphorus-doped silica films

Hybrid phosphorus-doped silica films have been prepared through sol?Cgel processes to enhance the thermal and fire stability of cotton. To this aim, 3-aminopropyltriethoxysilane and N,N,N??,N??,N??,N??-hexakis-methoxymethyl-[1,3,5]triazine-2,4,6-triamine have been reacted with diethylphosphatoethyltriethoxysilane. FT-IR spectroscopy was exploited for assessing the formation of the silica skeleton on the cotton surface and for evaluating the interactions between the cellulosic fibres and the doped film. The effect of the concurrent presence of Si, P and N on cotton has been investigated by thermogravimetric analyses and the flammability behaviour has been assessed by vertical flammability tests, as well. The sol?Cgel treatments in the presence of phosphorus and nitrogen turned out to play a protective role on the degradation of the cotton fibres, hindering the formation of volatile species that fuel the further degradation and favouring the formation of a carbonaceous structure.     

Degradation of poly(lactide-co-glycolide) and its composites with carbon fibres and hydroxyapatite in rabbit femoral bone

The aim of the present work was to analyse the degradation rate of PGLA copolymer depending on a modifier (hydroxyapatite, carbon fibres) under in vivo conditions (rabbit femoral bone). Also, the influence of the implantation site on the degradation rate of a copolymer (rabbit mandible and femoral bone) was analyzed as a continuation of our previous research.The structural and phase changes of poly(lactide-co-glycolide) and its composite with hydroxyapatite and carbon fibres were determined on the basis of IR and NMR spectroscopy. Additionally, microscopic observations with elemental analyses were performed (SEM, EDS).The addition of a modifying phase accelerates implant degradation. However, modifying additives promote regeneration of the treated bone tissue simultaneously with faster polymer degradation. The compositions of a copolymer and composites are variable during degradation.The process of copolymer degradation in the femoral bone is much faster in comparison with previous studies on mandibles. This may be caused by higher activity of osteoblasts, differences in blood supply and oxygenation of tissue as well as different anatomical structure of these two kinds of bones.FTIR and NMR methods allow for following the changes occurring in the resorbable copolymer structure with time and they are very useful tools in analyzing the degradation mechanism and rate of aliphatic polyesters and their composites.     

Raman spectroelectrochemical study on the kinetics of electrochemical degradation of polyaniline

The kinetics of electrochemical degradation of polyaniline and a copolymer of aniline and metanilic acid have been studied by in situ Raman spectroscopy at a gold electrode. It has been concluded that probably no drastic changes in polymer structure occur on prolonged electrochemical treatment of polymer films at a high electrode potential (0.8 V vs. Ag/AgCl). Instead, most prominent changes relate to a gradual decrease of an overall intensity of spectra, viz. to gradual degradation of a polymer layer. The degradation proceeds faster at pH 1.0, compared to pH 7.0. The kinetic results obtained have been analyzed following simple 2- or 3-parameter exponential decay equations, and compared with the known degradation rate constants.     

In-line rheometry of polypropylene based Wood Polymer Composites

A completely satisfactory off-line rheological investigation of Wood Polymer Composites (WPCs) is very challenging at processing temperatures: when using rotational rheometry in oscillatory mode, the linear viscoelastic region is often too small, while in capillary rheometry the sieving effect of the fibres may invalidate the results. Moreover, all off-line tests present the risk of wood degradation.To this aim, an in-line extrusion rheometer (slit die) has been developed. The major advantages are that the measurements are made in real processing conditions and degradation problems are less severe thanks to reduced oxygen level inside the extruder barrel.In order to verify the methodology, tests have been conducted on a commercial polypropylene based WPC with 30 wt.% white fir fibres and compared with off-line measurements performed at a lower temperature on the same material. For comparison, a temperature shift factor has been used, that has been estimated by characterizing the polypropylene matrix alone.     

Thermal stability and lifetime estimates of a high temperature epoxy by Tg reduction

Thermal degradation of a high temperature epoxy network is studied in terms glass transition temperature (T_g) reduction over a temperature window encompassing the T_g of the network. The T_g is shown to decrease as the network is thermally aged at elevated temperatures in air and in argon. The duration of the aging experiments is extended to long time such that the absolute T_g reduction approaches a long time reduction plateau. Degradation is dominated by non-oxidative pyrolysis with a small contribution from diffusion limited thermal oxidative degradation at the surface. A time–temperature superposition is constructed from the extent of T_g reduction of samples aged in air and the thermal shift factors are shown to have Arrhenius scaling behavior. An activation energy is extracted that agrees with previous activation energy measurements derived from other property measurements of the same network aged under similar conditions. The agreement of the activation energy with past results shows that T_g reduction is controlled by the same degradation mechanism and may be used as an observable for lifetime estimates when thermal degradation is pyrolytic in nature. The extent of T_g reduction is modeled with an autocatalytic rate expression and compared to previous property measurements to show the difference in sensitivity of observable material properties on degradation.     

A comparison of the increased temperature accelerated degradation of Poly(d,l-lactide-co-glycolide) and Poly(l-lactide-co-glycolide)

Bioresorbable polymers composed of Poly(lactide), Poly(glycolide) and their related copolymers have become increasingly popular for the preparation of bone substitute constructs. In vitro tests assessing the degradative changes in physicochemical, mechanical, and biological properties of bioresorbable polymers are generally carried out at 37 °C, in pH 7.4 phosphate-buffered saline (PBS). However, long degradation times, varying from months to years make it difficult to assess these polymers at their late stages of degradation. An increased temperature accelerated degradation methodology, that simulates the long-term degradation of Poly(d,l-lactide-co-glycolide) and Poly(l-lactide-co-glycolide), has been validated in this study. Samples were degraded in PBS, under sterile conditions. Degradation temperatures of 47 °C, 57 °C and 70 °C were selected and compared to physiological temperature, 37 °C. At predetermined time intervals, samples were retrieved and evaluated for changes in mass, swelling, molecular weight, crystallinity, and thermal properties. The results from this study suggest that the degradation mechanism at elevated temperatures is similar to that observed at 37 °C. It is recommended that 47 °C is adopted by the research community to accelerate the degradation of these polymers. It is hoped the application of this methodology could be used as a valuable tool, prior to the assessment of the long-term biocompatibility of these polymers.     

Aspects of Degradation Kinetics of Azithromycin in Aqueous Solution

The chemical stability of azithromycin (AZM) in aqueous solution has been investigated utilizing a stability-indicating LC assay with ultraviolet detection. The degradation kinetics were studied as functions of pH (4–7.2), buffer composition (phosphate, acetate, and citrate), buffer concentration, ionic strength, drug concentration and temperature. The observed rate obtained by measuring the remaining intact AZM was shown to follow pseudo-first-order kinetics. The maximum stability of AZM occured at an approximate pH 6.3 in 0.05 M potassium phosphate. The observed degradation rate increased with ionic strength, buffer concentration and obeyed the Arrhenius equation over the temperature range investigated (70–100 °C). The apparent energy of activation (E _a) for AZM in solution was found to be 96.8 kJ mol^?1 and by application of the Arrhenius equation the stability at 25 °C (k ₂₅) and 40 °C (k ₄₀) had been predicted. Moreover, the degradation rate of AZM was independent on its initial concentration. Trace metal ions are unlikely to be involved in the degradation of AZM in aqueous solution. The major degradation product of AZM in aqueous solution was isolated and identified by LC–MS–MS and ¹H and ¹³C NMR spectra.     

The acidity functions of trifluoroethanol and hexafluoroisopropanol,and their mixtures with water

Acidity measurements in trifluoroethanol and hexafluoroisopropanol as solvents, and in their mixtures with water, are reported. The hydrogen electrode and the glass electrode were used for pH measurements. The “experimental” autoprotolysis constants were determined from measurements in strongly acidic (trifluoromethanesulfonic) media and in strongly basic (alcoholate) media: for trifluoroethanol, pK = -log K/mol² l^-2 = 15 and for hexafluoroisopropanol, pK = 14.8. Evaluation of the pH-indicator potential systems with reference to the ferrocene/ferricinium couple gives the acidity function R₀(H). The values obtained are compared to the H₀ values evaluated in the same conditions.     

Simultaneous spectrophotometric flow-through measurements of pH, carbon dioxide fugacity, and total inorganic carbon in seawater

An autonomous multi-parameter flow-through CO₂ system has been developed to simultaneously measure surface seawater pH, carbon dioxide fugacity (fCO₂), and total dissolved inorganic carbon (DIC). All three measurements are based on spectrophotometric determinations of solution pH at multiple wavelengths using sulfonephthalein indicators. The pH optical cell is machined from a PEEK polymer rod bearing a bore-hole with an optical pathlength of ∼15 cm. The fCO₂ optical cell consists of Teflon AF 2400 (DuPont) capillary tubing sealed within the bore-hole of a PEEK rod. This Teflon AF tubing is filled with a standard indicator solution with a fixed total alkalinity, and forms a liquid core waveguide (LCW). The LCW functions as both a long pathlength (∼15 cm) optical cell and a membrane that equilibrates the internal standard solution with external seawater. fCO₂ is then determined by measuring the pH of the internal solution. DIC is measured by determining the pH of standard internal solutions in equilibrium with seawater that has been acidified to convert all forms of DIC to CO₂. The system runs repetitive measurement cycles with a sampling frequency of ∼7 samples (21 measurements) per hour. The system was used for underway measurements of sea surface pH, fCO₂, and DIC during the CLIVAR/CO₂ A16S cruise in the South Atlantic Ocean in 2005. The field precisions were evaluated to be 0.0008 units for pH, 0.9 μatm for fCO₂, and 2.4 μmol kg⁻¹ for DIC. These field precisions are close to those obtained in the laboratory. Direct comparison of our measurements and measurements obtained using established standard methods revealed that the system achieved field agreements of 0.0012 ± 0.0042 units for pH, 1.0 ± 2.5 μatm for fCO₂, and 2.2 ± 6.0 μmol kg⁻¹ for DIC. This system integrates spectrophotometric measurements of multiple CO₂ parameters into a single package suitable for observations of both seawater and freshwater.     

Polymer immobilized Fe(III) complex of 2-phenylbenzimidazole: An efficient catalyst for photodegradation of dyes under UV/Visible light irradiation

Fe(III) complex of 2-phenylbenzimidazole has been covalently anchored on polymer and characterized by elemental analysis, FT-IR, far-IR, BET surface area measurements, UV–Vis/DRS spectroscopy, thermo-gravimetric analysis and magnetic moment measurements by VSM which confirmed an octahedral environment around Fe(III) in the bound complex. The photocatalytic performance of this complex was evaluated in the photodegradation of dyes in presence of H₂O₂ as an oxidizing agent. Suitable reaction conditions have been optimized by considering the effects of various reaction parameters such as pH, oxidants, concentration of dye, H₂O₂ and catalyst for the maximum degradation of dye. The photodegradation was found to be 100% with complete mineralization in 150?min. The comparison of photocatalytic efficiency of the catalyst under visible light, sunlight and dark conditions are accomplished. Comparison between catalytic activity of the polymer-supported complex and unbound complex demonstrated that the polymer-supported complex was more active. Photocatalytic performance of PS-Fe(III)PBMZL was also compared with commercial TiO₂ (P25). This heterogeneous complex retained its activity up to 8 runs. A tentative mechanism has been proposed.     

Acetone extracted propolis as a novel membrane and its application in phenol biosensors: the case of catechol

A novel biosensor for catechol has been constructed by immobilizing polyphenol oxidase (PPO) into acetone-extracted propolis (AEP) composite modified with gold nanoparticles (GNPs) and attached to multiwalled carbon nanotube (MWCNTs) on a gold electrode surface. The propolis for AEP was obtained from honeybee colonies. Under the optimum conditions, this method could be successfully used for the amperometric determination of catechol within a concentration range of 1 × 10^?6 to 5 × 10^?4?M, with a detection limit of 8 × 10^?7?M (S/N = 3). The effects of pH and operating potential are also explored to optimize the measurement conditions. The best response was obtained at pH?5, while an optimum ratio of signal-to-noise (S/N) was obtained at ?20?mV (versus Ag/AgCl), which was selected as the applied potential for the amperometric measurements. All subsequent experiments were performed at pH?5. Cyclic voltammetry and electrochemical impedance spectroscopy was used to characterize the PPO/CNTs/GNPs/AEP/Au biosensor. The biosensor also exhibited good selectivity, stability, and reproducibility.     

A Fast and Simple Screening Method for m-Nisoldipine and Its Related Substances by MEKC

A rapid and simple method has been developed and validated for the determination of m-nisoldipine and its five related substances using micellar electrokinetic capillary chromatography (MEKC). The key factors, including pH, buffer concentration and buffer additive, sodium dodecyl sulfate (SDS) concentration, applied voltage and temperature were systematically investigated in an uncoated fused silica capillary. The total analysis time was less than 9 min. The forced degradation products of m-nisoldipine, which were induced by hydrogen peroxide, acidic and basic conditions, heat and light, were also tested.     

Structure and mechanism formation of polyelectrolyte complex obtained from PSS/PAH system: effect of molar mixing ratio, base–acid conditions, and ionic strength

Colloidal dispersions of polyelectrolyte complexes were prepared in aqueous solutions. We have used mixtures containing the strongly charged anionic polyelectrolyte sodium polystyrene sulfonate (PSS) and the weak cationic polyelectrolyte polyallylamine hydrochloride (PAH). Both polymers have the same molecular weight. The complexes were obtained by adding drop by drop a solution of the anionic polyelectrolyte to excess cationic polyelectrolyte. In these conditions, sodium polystyrene sulfonate and polyallylamine hydrochloride self-assembled in nanometer-range complexes; the self-assembly is driven by electrostatic interactions, as well as by entropy changes due to counterion release. The electrostatic interactions were controlled in several ways: by changing the C _PSS/C _PAH concentration ratio, by modifying the pH (and thus the protonation degree of polyallylamine hydrochloride), and by adding sodium chloride (screened interactions). Dynamic light scattering experiments demonstrated that the hydrodynamics radius of the polyelectrolyte complex increases, changing from soluble to insoluble complex formation, when some physicochemical parameters are increased: the concentration ratio between polyelectrolytes, the sodium chloride concentration, and pH. Zeta potential measurements, as a function of the C _PSS/C _PAH concentration ratio, as well as of pH and ionic strength, allow us to state that the resulting particles have a structure constituted by a neutral core surrounded by a positively charged shell. The polyelectrolyte complexes have globular shapes, as observed by electron microscopy.     

Buffers for the Physiological pH Range: Studies of 4-(N-Morpholino)butanesulfonic Acid (MOBS) from 5 to 55 °C

In this study, we report the pH values of two buffer solutions without chloride ion and eight buffer solutions with NaCl with an ionic strength I=0.16 mol?kg^?1. Electromotive force (emf) techniques have been used to get the cell potentials at 12 temperatures from 5 to 55?°C, including 37?°C. An extended form of the Bates-Guggenheim convention is used in the entire ionic strength range, 0.04 to 0.16?mol?kg^?1. The residual liquid junction potentials (??E _j ) of the buffer solutions of MOBS have been estimated from previous measurements with a flowing junction cell. These values of ??E _j have been used for correction in order to ascertain the operational pH values of four buffer solutions of MOBS at 25 and 37?°C. These solutions are recommended as pH standards for physiological application in the pH range 7.4 to 7.7.     

Electrospinning of α,β-poly(N-2-hydroxyethyl)-dl-aspartamide-graft-polylactic acid to produce a fibrillar scaffold

α,β-Poly(N-2-hydroxyethyl)-dl-aspartamide grafted with polylactic acid (PHEA-g-PLA) is a biocompatible and biodegradable amphiphilic copolymer that has been already employed to prepare a drug delivery system.In this study we have prepared for the first time a fibrillar scaffold from PHEA-g-PLA by the electrospinning of a solution of this copolymer in a mixture of N,N-dimethyl formamide (DMF) and acetone (80:20 vol/vol). The average diameter and the morphology of electrospun fibers were detected by scanning electron microscopy.Chemical degradation studies in phosphate buffer solution pH 7.4 have been performed until 15 days in order to obtain a preliminary information about the hydrolytic resistance of the prepared scaffold.