Europium(III) Meets Etidronic Acid (HEDP): A Coordination Study Combining Spectroscopic, Spectrometric, and Quantum Chemical Methods.

Etidronic acid (1-Hydroxyethylidene-1,1-diphosphonic acid, HEDP, H4L) is a proposed decorporation agent for U(VI). This paper studied its complex formation with Eu(III), an inactive analog of trivalent actinides, over a wide pH range, at varying metal-to-ligand ratios (M:L) and total concentrations. Combining spectroscopic, spectrometric, and quantum chemical methods, five distinct Eu(III)-HEDP complexes were found, four of which were characterized. The readily soluble EuH2L+ and Eu(H2L)2- species with log ß values of 23.7 ± 0.1 and 45.1 ± 0.9 are formed at acidic pH. At near-neutral pH, EuHL0s forms with a log ß of ~23.6 and, additionally, a most probably polynuclear complex. The readily dissolved EuL- species with a log ß of ~11.2 is formed at alkaline pH. A six-membered chelate ring is the key motif in all solution structures. The equilibrium between the Eu(III)-HEDP species is influenced by several parameters, i.e., pH, M:L, total Eu(III) and HEDP concentrations, and time. Overall, the present work sheds light on the very complex speciation in the HEDP-Eu(III) system and indicates that, for risk assessment of potential decorporation scenarios, side reactions of HEDP with trivalent actinides and lanthanides should also be taken into account.

Investigation of Physical Properties of Disodium Etidronate Tetrahydrate and Application of Phosphorus K-Edge X-Ray Absorption Near-Edge Structure Spectroscopy.

PURPOSE: Disodium etidronate is a bisphosphonate, compounds that are widely used in the treatment of bone disorders such as osteoporosis and Paget's disease. We investigated the physical properties of disodium etidronate tetrahydrate crystal, form I. METHODS: We used X-ray powder diffraction (XRPD), thermal analysis, dynamic vapor sorption (DVS), X-ray single crystal structure analysis, and phosphorus K-edge X-ray absorption near-edge structure (XANES) spectroscopy for the first time. RESULTS: XRPD and thermal analyses demonstrated that form I was dehydrated and transformed to an amorphous form, to a crystalline form II, and finally to a form III by heating. DVS measurements revealed that the amorphous form, form II, and form III were rehydrated to form I by humidification, and form I was stable even at 0% relative humidity. These results indicate that form I is the most stable solid-state under ambient conditions and is suitable as an API for manufacture in solid formulations. The phosphorus K-edge XANES spectra differed among form I, the amorphous form, and form II, which may be ascribed to the difference in the coordinate bond schemes between the phosphate moieties and sodium ions. The results demonstrated that the phosphorus K-edge XANES spectroscopy could be applied to the identification or the discrimination of crystal forms of the APIs containing phosphate moieties. CONCLUSIONS: Acquired information about physical properties are crucial for manufacturing of solid formulations of disodium etidronate. XANES spectroscopy is a promising alternative method for evaluating the solid-state forms of APIs.

Batch Studies of Phosphonate and Phosphate Adsorption on Granular Ferric Hydroxide (GFH) with Membrane Concentrate and Its Synthetic Replicas.

Phosphonates are widely used as antiscalants for softening processes in drinking water treatment. To prevent eutrophication and accumulation in the sediment, it is desirable to remove them from the membrane concentrate before they are discharged into receiving water bodies. This study describes batch experiments with synthetic solutions and real membrane concentrate, both in the presence of and absence of granular ferric hydroxide (GFH), to better understand the influence of ions on phosphonate and phosphate adsorption. To this end, experiments were conducted with six different phosphonates, using different molar Ca:phosphonate ratios. The calcium already contained in the GFH plays an essential role in the elimination process, as it can be re-dissolved, and, therefore, increase the molar Ca:phosphonate ratio. (Hydrogen-)carbonate ions had a competitive effect on the adsorption of phosphonates and phosphate, whereas the influence of sulfate and nitrate ions was negligible. Up to pH 8, the presence of CaII had a positive effect on adsorption, probably due to the formation of ternary complexes. At pH > 8, increased removal was observed, with either direct precipitation of Ca:phosphonate complexes or the presence of inorganic precipitates of calcium, magnesium, and phosphate serving as adsorbents for the phosphorus compounds. In addition, the presence of (hydrogen-)carbonate ions resulted in precipitation of CaCO3 and/or dolomite, which also acted as adsorbents for the phosphorus compounds.

Leaching Behaviour and Enhanced Phytoextraction of Additives for Cadmium-Contaminated Soil by Pennisetum sp.

The leaching behavior of five additives, including citric acid (CA), wood vinegar (WV), 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP), polyaspartic acid (PASP) and FeCl3, was investigated to evaluate the possibility of enhanced phytoextraction of Pennisetum sp. from cadmium-contaminated soil. FeCl3 and CA have the highest leaching potential due to the ability that could convert large amounts of mobile fractions of Cd. The pot experiment showed that HEDP, WV, and PASP treatments could not only significantly increase the biomass of Pennisetum sp., but also maintain high uptake capacity of Cd by activating the stable fractions. HEDP has the highest Cd extraction efficiency and metal extraction ratio (MER) value. The phytoremediation efficiency could be improved mainly by increasing the biomass of the tolerant shoots, and Pennisetum sp. seems to have the maximum potential of phytoextraction to Cd with HEDP which could achieve a higher phytoextraction effect than Cd-hyperaccumulator.

Short-term storage stability of NaOCl solutions when combined with Dual Rinse HEDP.

AIM: To assess the stability of NaOCl solutions when combined with a novel product for clinical use, Dual Rinse HEDP, which contains etidronate (1-hydroxyethane 1,1-diphosphonate). METHODOLOGY: Mixtures of NaOCl solutions with Dual Rinse HEDP were prepared so that they initially contained 5.0%, 2.5% or 1.0% NaOCl and always 9.0% of dissolved Dual Rinse HEDP powder per total weight. NaOCl solutions alone were used as controls. The stability of these solutions over 8 h was assessed in transparent borosilicate glass bottles at ambient temperature (23 °C). Subsequently, the effects of heating (60 °C) or storing the solutions at 5 °C were studied in polypropylene syringes. NaOCl concentrations were measured by iodometric titration, that is free available chlorine contents. Experiments were performed in triplicate. RESULTS: In the glass bottles at 23 °C, the 5.0% NaOCl/9.0% Dual Rinse HEDP solution lost 20% of the available chlorine after 1 h, whilst the corresponding 2.5% NaOCl and 1.0% NaOCl solutions retained this relative amount of available chlorine for 2 and 4 h, respectively. Results obtained in the glass bottles were similar to those achieved in the syringes. Heating of the NaOCl/Dual Rinse HEDP mixtures had a detrimental effect on available chlorine, with a complete loss after 1 h. In contrast, storing the NaOCl/Dual Rinse HEDP mixtures in a refrigerator at 5 °C kept the available chlorine high for 7 h, with the expected loss after a further hour of storage at 23 °C. CONCLUSIONS: Initial NaOCl concentration and temperature both affected short-term storage stability of combined solutions containing Dual Rinse HEDP.

An IC-MS/MS Method for the Determination of 1-Hydroxyethylidene-1,1-diphosphonic Acid on Uncooked Foods Treated with Peracetic Acid-Based Sanitizers.

A rapid, sensitive, and specific analytical method for the determination of 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) on uncooked foods after treatment with a peracetic acid-based sanitizer (PAS) was developed. The method involves simple sample preparation steps and analysis using ion chromatography (IC) coupled with tandem mass spectrometry (MS/MS). The quantification limits of HEDP on uncooked foods are 0.007 mg/kg for vegetables and fruits and 0.2 mg/kg for meats. The recovery and relative standard deviation (RSD) of HEDP analyses of uncooked foods ranged from 73.9 to 103.8% and 1.9 to 12.6%, respectively. The method's accuracy and precision were evaluated by inter-day recovery tests. The recovery for all samples ranged from 93.6 to 101.2%, and the within-laboratory repeatability and reproducibility were evaluated based on RSD values, which were less than 6.9 and 11.5%, respectively. Analyses of PAS-treated fruits and vegetables using the developed method indicated levels of HEDP ranging from 0.008 to 0.351 mg/kg. Therefore, the results of the present study suggest that the proposed method is an accurate, precise, and reliable way to determine residual HEDP levels on PAS-treated uncooked foods.

Synthesis of acid-stabilized iron oxide nanoparticles and comparison for targeting atherosclerotic plaques: evaluation by MRI, quantitative MPS, and TEM alternative to ambiguous Prussian blue iron staining.

To further optimize citrate-stabilized VSOPs (very small iron oxide particles, developed for MR angiography) for identification of atherosclerotic plaques, we modified their surface during synthesis using eight other acids for electrostatic stabilization. This approach preserves effective production for clinical application. Five particles were suitable to be investigated in targeting plaques of apoE(-/-) mice. Accumulation was evaluated by ex vivo MRI, TEM, and quantitatively by magnetic particle spectroscopy (MPS). Citric- (VSOP), etidronic-, tartaric-, and malic-acid-coated particles accumulated in atherosclerotic plaques with highest accumulation for VSOP (0.2‰ of injected dose). Targets were phagolysosomes of macrophages and of altered endothelial cells. In vivo MRI with VSOP allowed for definite plaque identification. Prussian blue staining revealed abundant endogenous iron in plaques, indistinguishable from particle iron. In apoE(-/-) mice, VSOPs are still the best anionic iron oxide particles for imaging atherosclerotic plaques. MPS allows for quantification of superparamagnetic nanoparticles in such small specimens. FROM THE CLINICAL EDITOR: The presence of vulnerable plaques in arteries is important for the prediction of acute coronary events. VSOP (very small iron oxide particles, developed for MR angiography) have been shown to be very sensitive in identifying atherosclerotic plaques. The authors studied here further modification to the surface of VSOP during synthesis and compared their efficacy.

Lipophilic analogs of zoledronate and risedronate inhibit Plasmodium geranylgeranyl diphosphate synthase (GGPPS) and exhibit potent antimalarial activity.

We report the results of an in vitro screening assay targeting the intraerythrocytic form of the malaria parasite Plasmodium falciparum using a library of 560 prenyl-synthase inhibitors. Based on "growth-rescue" and enzyme-inhibition experiments, geranylgeranyl diphosphate synthase (GGPPS) is shown to be a major target for the most potent leads, BPH-703 and BPH-811, lipophilic analogs of the bone-resorption drugs zoledronate and risedronate. We determined the crystal structures of these inhibitors bound to a Plasmodium GGPPS finding that their head groups bind to the [Mg(2+)](3) cluster in the active site in a similar manner to that found with their more hydrophilic parents, whereas their hydrophobic tails occupy a long-hydrophobic tunnel spanning both molecules in the dimer. The results of isothermal-titration-calorimetric experiments show that both lipophilic bisphosphonates bind to GGPPS with, on average, a ΔG of -9 kcal mol(-1), only 0.5 kcal mol(-1) worse than the parent bisphosphonates, consistent with the observation that conversion to the lipophilic species has only a minor effect on enzyme activity. However, only the lipophilic species are active in cells. We also tested both compounds in mice, finding major decreases in parasitemia and 100% survival. These results are of broad general interest because they indicate that it may be possible to overcome barriers to cell penetration of existing bisphosphonate drugs in this and other systems by simple covalent modification to form lipophilic analogs that retain their enzyme-inhibition activity and are also effective in vitro and in vivo.

Adsorption on apatitic calcium phosphates for drug delivery: interaction with bisphosphonate molecules.

Bisphosphonates (BPs) are well established as an important class of drugs for the treatment and prevention of several bone disorders including osteoporosis. This work investigated the interaction of two bisphosphonates, risedronate and tiludronate, with several apatitic supports, a well-crystallised hydroxyapatite (HA) and nanocrystalline apatites with varying maturation times, chemical composition and surface characteristics. The purpose was to fully understand the adsorption mechanism and desorption process, by the evaluation of the effect of several physicochemical parameters (temperature, pH and concentration of calcium and phosphate ions). Whatever the nature of the BP and the structure and composition of the apatite, the adsorption of such anti-resorptive agents can be well described as an ion exchange-reaction between phosphates species on the apatitic surface and BP molecules in solution. However, the parameters of adsorption can vary depending on the physicochemical conditions of the adsorption reaction. In addition, the structure and composition of the apatitic surface also influence the adsorption properties. Finally, BPs molecules are slowly released from apatitic supports, because most of the adsorbed molecules are irreversibly bound and not spontaneously released by dilution or simple washing. Moreover, similar to their adsorption, the release of bisphosphonates is strongly affected not only by the chemical properties of the molecule, but also by the chemical and structural characteristics of the apatitic substrates. The understanding of the adsorption and release processes provides fundamental tools for the development of drug delivery systems using apatite materials.

Preparation of risedronate nanoparticles by solvent evaporation technique.

One approach for the enhancement of oral drug bioavailability is the technique of nanoparticle preparation. Risedronate sodium (Biopharmaceutical Classification System Class III) was chosen as a model compound with high water solubility and low intestinal permeability. Eighteen samples of risedronate sodium were prepared by the solvent evaporation technique with sodium dodecyl sulfate, polysorbate, macrogol, sodium carboxymethyl cellulose and sodium carboxymethyl dextran as nanoparticle stabilizers applied in three concentrations. The prepared samples were characterized by dynamic light scattering and scanning electron microscopy. Fourier transform mid-infrared spectroscopy was used for verification of the composition of the samples. The particle size of sixteen samples was less than 200 nm. Polysorbate, sodium carboxymethyl dextran and macrogol were determined as the most favourable excipients; the particle size of the samples of risedronate with these excipients ranged from 2.8 to 10.5 nm.

Bisphosphonate Liposomes for Cobalt and Strontium Decorporation?

ABSTRACT: During a nuclear/radiological incident or an accident involving internal intakes with radioactive cobalt or strontium, the recommended treatments, consisting of the administration of diethylenetriaminepentaacetic acid for 60 Co and calcium gluconate for 90 Sr, are of low specificity, and their effectiveness can be enhanced. In this manuscript, a liposomal formulation was developed to deliver potential chelating agents to the main retention organs of both radionuclides. A bisphosphonate, etidronate, has been selected as a possible candidate due to its satisfying decorporation activity for uranium, bone tropism, and potential affinity with cobalt. Pre-clinical studies have been carried out on rats using radionuclide contamination and treatment administration by the intravenous route. The effectiveness of free or liposomal etidronate was evaluated, with an administration at 30 min, 48 h post-contamination with 60 Co. Regarding 85 Sr, a more extended experiment with etidronate liposomes was performed over 6 d. The results were compared to those performed with reference treatments, diethylenetriaminepentaacetic acid for cobalt and calcium gluconate for strontium. Unexpected results were found for the reference treatments that were significantly less effective than previously reported or showed no effectiveness. Free etidronate revealed no significant efficacy after 48 h, but the liposomal form suggested an interaction with radionuclides, not sufficient to change the biokinetics. This study emphasizes the need for early treatment administration and further research to provide a more effective medical countermeasure.

Novel fluorescent risedronates: synthesis, photodynamic inactivation and imaging of Bacillus subtilis.

Novel fluorescently-labeled conjugates of risedronate were synthesized using an epoxide linker, enabling conjugation of risedronate via its pyridyl nitrogen with the aromatic succinimidyl esters. The compounds were characterized by using (1)H NMR, (13)C NMR, (31)P NMR, UV-vis and fluorescence emission spectroscopies. Biological activity assays showed that the conjugates 14 and 15 exhibited photodynamic inactivation of Bacillus subtilis (ATCC 6633) with 91% and 47% bacterial lethality at 10 µM upon visible light irradiation, respectively. Both 14 and 15 could be also used for fluorescence imaging of Bacillus subtilis.

Inhibition of phosphate transporters ameliorates the inflammatory and necrotic side effects of the nitrogen-containing bisphosphonate zoledronate in mice.

Bisphosphonates (BPs) are pyrophosphate analogs. They are widely used against enhanced bone-resorption in various diseases. Nitrogen-containing BPs (N-BPs) exhibit strong anti-bone-resorptive effects but have inflammatory and necrotic side effects. The non-nitrogen-containing BPs (non-N-BPs) etidronate and clodronate lack such side effects, but their anti-bone-resorptive effects are weak. In mice, etidronate and clodronate reduce the inflammatory/necrotic effects of N-BPs, even those of zoledronate, the N-BP with the strongest anti-bone-resorptive effect yet reported and the highest risk of inflammation/necrosis. Here, to explore the mechanisms underlying this protection, we used a mouse model in which a single reagent or a mixture of two reagents was injected subcutaneously into ear-pinnas. These reagents included zoledronate, four non-N-BPs, pyrophosphate, and inhibitors of various organic-anion-transporters. Pyrophosphate and two of the four non-N-BPs (not etidronate or clodronate) had inflammatory/necrotic effects. These effects were reduced by etidronate and clodronate, but not by phosphonoformate, an inhibitor of two of the three known phosphate-transporter families. Phosphonoformate reduced the inflammatory/necrotic effects of zoledronate, but not those of pyrophosphate or of non-N-BPs. Conversely, pyrophosphate, at non-inflammatory/necrotic concentrations, reduced the inflammatory/necrotic effects of non-N-BPs, but not those of zoledronate. The efficacies of the protective effects against the inflammatory/necrotic effects of zoledronate were clodronate > etidronate > phosphonoformate. These findings suggest that (i) the N-BP zoledronate may enter soft-tissue cells via phosphonoformate-inhibitable phosphate-transporters, (ii) other phosphate-transporters may carry pyrophosphate and inflammatory/necrotic non-N-BPs into such cells, and (iii) etidronate and clodronate inhibit all these transporters, and they ameliorate the side effects of zoledronate by inhibiting phosphonoformate-inhibitable phosphate-transporters.

Application of 1-hydroxyethylidene-1, 1-diphosphonic acid in boiler water for industrial boilers.

The primary method used for boiler water treatment is the addition of chemicals to industrial boilers to prevent corrosion and scaling. The static scale inhibition method was used to evaluate the scale inhibition performance of 1-hydroxyethylidene-1, 1-diphosphonic acid (HEDP). Autoclave static experiments were used to study the corrosion inhibition properties of the main material for industrial boilers (20# carbon steel) with an HEDP additive in the industrial boiler water medium. The electrochemical behavior of HEDP on carbon steel corrosion control was investigated using electrochemical impedance spectroscopy and Tafel polarization techniques. Experimental results indicate that HEDP can have a good scale inhibition effect when added at a quantity of 5 to 7 mg/L at a test temperature of not more than 100 °C. To achieve a high scale inhibition rate, the HEDP dosage must be increased when the test temperature exceeds 100 °C. Electrochemical and autoclave static experimental results suggest that HEDP has a good corrosion inhibition effect on 20# carbon steel at a concentration of 25 mg/L. HEDP is an excellent water treatment agent.

Hydrophilic versus hydrophobic porogens for engineering of poly(lactide-co-glycolide) microparticles containing risedronate sodium.

OBJECTIVE: The aim of this study was to investigate the effect of two mechanistically different porogens, namely: the hydrophilic hydroxy-propyl-ß-cyclodextrin and the hydrophobic porogens (mineral oil and corn oil) in producing open/closed pored engineered polylactide-co-glycolic-acid microspheres suitable for pulmonary delivery of risedronate sodium (RS). MATERIALS AND METHODS: Surface morphology of the microspheres was studied and they were characterized for entrapment efficiency (%EE), particle size, and porosity as well as aerodynamic and flow properties. Selected formulae were investigated for in vitro drug release and deposition behavior using next generation impactor. Furthermore, the safety of the free drug and the selected prepared systems was assessed by MTT viability test performed on Calu-3 cell line. RESULTS AND DISCUSSION: The current work revealed that HP-ß-CD produced open-pored microspheres, while oils produced closed pored microspheres. Modulation of preparation parameters generated porous RS microspheres with high %EE, sustained drug release profile up to 15 days, suitable geometric and aerodynamic particle sizes and excellent flow properties. The safety of HP-ß-CD systems was higher than the systems utilizing oil as porogen. CONCLUSION: Porogen type affected the behavior of the microspheres as demonstrated by the various characterization experiments, with microspheres prepared using HP-ß-CD being superior to those prepared using oils as porogens.

Comparison of the physical properties of disodium etidronate amorphous forms prepared by different manufacturing methods.

Amorphous forms of disodium etidronate were prepared by three manufacturing methods, heat drying, freeze drying, and anti-solvent precipitation, and the effects of these methods on the physical properties of disodium etidronate amorphous forms were evaluated for the first time. Variable temperature X-ray powder diffraction and thermal analyses revealed that these amorphous forms had different physical properties such as glass transition point, water desorption, and crystallization temperatures. These differences can be explained by the molecular mobility and water content in amorphous forms. The differences in the structural characteristics related to the differences in these physical properties could not be detected clearly by the spectroscopic methods like Raman spectroscopy and X-ray absorption near-edge spectroscopy. Dynamic vapor sorption analyses demonstrated that all amorphous forms were hydrated to form I, a tetrahydrated form, at above 50% relative humidity, and the transition to form I was irreversible. These amorphous forms require strict humidity control to avoid crystallization. Among the three amorphous forms of disodium etidronate, the amorphous form prepared by heat drying was the most suitable for manufacturing the solid formulation, considering the low water content and low molecular mobility.

Beyond Antiresorptive Activity: Risedronate-Based Coordination Complexes To Potentially Treat Osteolytic Metastases.

Coordination of clinically employed bisphosphonate, risedronate (RISE), to bioactive metals, Ca2+, Mg2+, and Zn2+, allowed the formation of bisphosphonate-based coordination complexes (BPCCs). Three RISE-based BPCCs, RISE-Ca, RISE-Mg, and RISE-Zn, were produced, and their structures were elucidated by single crystal X-ray diffraction. Interestingly, the addition of an auxiliary ligand, etidronic acid (HEDP), resulted in the recrystallized protonated form of the ligand, H-RISE. The pH-dependent structural stability of the RISE-based BPCCs was measured by means of dissolution profiles under neutral and acidic simulated physiological conditions (PBS and FaSSGF, respectively). In comparison to RISE (Actonel), the complexes showed a lower equilibrium solubility (∼70-85% in 18-24 h) in PBS, while a higher equilibrium solubility (∼100% in 3 h) in acidic media. The results point to the capacity to release this BP in a pH-dependent manner from the RISE-based BPCCs. Subsequently, the particle size of RISE-Ca was reduced, from 300 µm to ∼350 d.nm, employing the phase inversion temperature (PIT)-nanoemulsion method, resulting in nano-Ca@RISE. Aggregation measurements of nano-Ca@RISE in 1% fetal bovine serum (FBS):H2O was monitored after 24, 48, and 72 h to study the particle size longevity in physiological media, showing that the suspended material has the potential to maintain its particle size over time. Furthermore, binding assays were performed to determine the potential binding of nano-Ca@RISE to the bone, where results show higher binding (∼1.7×) for the material to hydroxyapatite (HA, 30%) when compared to RISE (17%) in 1 d. The cytotoxicity effects of nano-Ca@RISE were compared to those of RISE against the human breast cancer MDA-MB-231 and normal osteoblast-like hFOB 1.19 cell lines by dose-response curves and relative cell viability assays in an in vitro setting. The results demonstrate that nano-Ca@RISE significantly decreases the viability of MDA-MB-231 with high specificity, at concentrations ∼2-3× lower than the ones reported employing other third-generation BPs. This is supported by the fact that when normal osteoblast cells (hFOB 1.19), which are part of the tissue microenvironment at metastatic sites, were treated with nano-Ca@RISE no significant decrease in viability was observed. This study expands on the therapeutic potential of RISE beyond its antiresorptive activity through the design of BPCCs, specifically nano-Ca@RISE, that bind to the bone and degrade in a pH-dependent manner under acidic conditions.

H2O2/UV-C treatment of textile preparation wastewater: kinetic investigation on alternative combinations of commercial textile preparation auxiliaries.

Four different textile preparation effluents were simulated to examine the applicability of the hydrogen peroxide/ultraviolet-C (H2O2/UV-C) advanced oxidation process for the treatment of real textile preparation (desizing, scouring and bleaching) wastewater bearing the non-ionic surfactant nonyl phenol decaethoxylate (NP-10). In the absence of any textile preparation chemical, NP-10 degradation was complete in 15 min (rate coefficient: 0.22 min(-1)) accompanied by 78% chemical oxygen demand (COD) (rate coefficient: 0.026 min(-1)) and 57% total organic carbon (TOC) (rate coefficient: 0.014 min(-1)) removals achieved after 60 min photochemical treatment. H2O2 consumption rates were not significantly affected by the introduction of carbonate and chloride ions (average rate coefficient: 0.032 min(-1)) at pH values <11.5, above which H2O2 dissociation to its conjugate base HO2(-) became pronounced. The organic, phosphonate-based sequestering agents competed with NP-10 for UV-C light absorption and HO* radicals. H2O2/UV-C oxidation of the simulated textile preparation effluent containing 3.0 g L(-1) Cl(-), 1.5 g L(-1) NaOH and 1.0 g L(-1) diethylenetriamine pentamethylene phosphonic acid (DTPMP) resulted in the worst treatment performance due to its high pH and organic carbon content. For this textile preparation effluent, NP-10 abatement was complete in 100min (rate coefficient: 0.018 min(-1)), while COD and TOC removals dropped down to only 16% and 8%, respectively, achieved after 60 min treatment. The highest H2O2/UV-C oxidation efficiency resulting in 34% COD and 28% TOC removals was obtained for the simulated textile preparation effluent comprising of 3.0 g L(-1) Cl(-), 1.5 g L(-1) NaOH and 1.0 g L(-1) 1-hydroxy ethylidene-1,1-diphosphonic acid (HEDP). For this textile preparation effluent, NP-10 degradation was complete after 50 min (rate coefficient: 0.061 min(-1)) exposure to H2O2/UV-C treatment.

Crystallization products of risedronate with carbohydrates and their substituted derivatives.

The gastrointestinal absorption of bisphosphonates is in general only about 1%. To address this problem mixtures of risedronate monosodium salt with twelve varied sugar alcohols, furanoses, pyranoses and eight gluco-, manno- and galactopyranoside derivatives as counterions were designed in an effort to prepare co-crystals/new entities with improved intestinal absorption. Crystalline forms were generated by means of kinetically and/or thermodynamically controlled crystallization processes. One hundred and fifty-two prepared samples were screened by means of FT-NIR and FT-Raman spectroscopy. No co-crystal was prepared, but noteworthy results were obtained. A new solid phase of risedronate monosodium salt generated in the presence of phenyl-ß-d-galactopyranoside under thermodynamically controlled crystallization conditions was found and also characterized using solid state NMR spectroscopy, X-ray powder diffraction and differential scanning calorimetry. This new polymorph was named as form P. Interactions between risedronate monosodium salt and both carbohydrates were confirmed by means of molecular dynamics simulation. In the present study the relationships between the chemical structures of the studied compounds required for crystalline form change are discussed.

Mitigation of analyte loss on metal surfaces in liquid chromatography.

The adsorptive loss of acidic analytes in liquid chromatography was investigated using metal frits. Repetitive injections of acidic small molecules or an oligonucleotide were made on individual 2.1 or 4.6 mm i.d. column frits. Losses were observed for adenosine 5'-(α,ß-methylene) diphosphate, 2-pyridinol 1-oxide and the 25-mer phosphorothioate oligonucleotide Trecovirsen (GEM91) on stainless steel and titanium frits. Analyte adsorption was greatest at acidic pH due to the positive charge on the metal oxide surface. Analyte recovery increased when a series of injections was performed; this effect is known as sample conditioning. Nearly complete recovery was achieved when the metal adsorptive sites were saturated with the analyte. A similar effect was achieved by conditioning the frits with phosphoric, citric or etidronic acids, or their buffered solutions. These procedures can be utilized to mitigate analyte loss. However, the effect is temporary, as the conditioning agent is gradually removed by the running mobile phase. Metal frits modified with hybrid organic/inorganic surface technology were shown to mitigate analyte-to-metal surface interactions and improve recovery of acidic analytes. Quantitative recovery of a 15-35 mer oligodeoxythymidine mixture was achieved using column hardware modified with hybrid surface technology, without a need for column conditioning prior to analysis.