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Retrospective/accidental dosimetry seeks for materials that can be used as probes for the dose assessment by means of several methods when there is no dose data available (e.g. from personal dosimeters). In the same respect, researchers also seek materials appropriate for forensic purposes, which would allow to identify the prior presence of radioactive materials at buildings, sites or even vehicles. To this direction, several solid-state drugs, which are ubiquitous, have also been studied as probes for the dose estimation in emergency situations. However, due to their heat-sensitive character, measurements were possible only with OSL. The scope of the present work is to identify a heat-resistant drug (Daktarin) and conduct, for the first time, a detailed study of the thermoluminescence properties of it along with computerized curve deconvolution analysis which would shed light on the traps involved. Results indicate that the glow curve of Daktarin has at least three peaks that can be used for dosimetric purposes, since they exhibit linear dose response for doses up to 20 Gy, do not exhibit any sensitization, have high lifetime and their stability with time is good, since an appreciable signal remains unaffected even 3 months post irradiation. All the above were validated conducting dose recovery tests and successfully calculating the unknown delivered dose for various periods after the irradiation of the samples. The new findings are very supportive and point towards the efficient use of commercial pharmaceuticals as probes for retrospective/accidental/forensic dosimetry using thermoluminescence., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A series of well-defined N-glycosylated IgG4-Fc variants were utilized to investigate the effect of glycan structure on their physicochemical properties (conformational stability and photostability) and interactions with an Fc γ receptor IIIA (FcγRIIIA). High mannose (HM, GlcNAc 2 Man (8+n) [n = 0-4]), Man 5 (GlcNAc 2 Man 5 ), GlcNAc 1 , and N297Q IgG4-Fc were prepared in good quality. The physical stability of these IgG4-Fc variants was examined with differential scanning calorimetry and intrinsic fluorescence spectroscopy. Photostability was assessed after photoirradiation between 295 and 340 nm (λ max  = 305 nm), and HPLC-MS/MS analysis of specific products was performed. The size of glycans at Asn 297 affects the yields of light-induced Tyr side-chain fragmentation products, where the yields decreased in the following order: N297Q > GlcNAc 1 > Man 5 > HM. These yields correlate with the thermal stability of the glycoforms. The HM and Man 5 glycoforms display increased affinity for FcγRIIIA by at least 14.7-fold compared with GlcNAc 1 IgG4-Fc. The affinities measured for the HM and Man 5 IgG4-Fc (0.39-0.52 μM) are similar to those measured for fucosylated IgG1. Dependent on the mechanisms of action of IgG4 therapeutics, such glycoforms may need to be carefully monitored. The nonglycosylated N297Q IgG4-Fc did not present measurable affinity to FcγRIIIA., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

We present here the development of a photochemical model used to quantify the risk to photodegradation of a solid drug substance. A key feature of the proposed model development is streamlined estimation of the dependence of the absorption spectra and the quantum yield to the wavelength. A mathematical description of the relationship between the quantum yield and the wavelength enables estimation of photodegradation kinetics under any light anticipated to be encountered in the manufacturing environment. The system studied here consisted of a first order irreversible transformation (A → B(1Φ)) and the formalism strongly suggested the quantum yield was constant over the relevant wavelength range. The predictive power of the model enabled the design of a control strategy to limit the formation of the photo-degradant to very low levels. Also presented are insights obtained from quantum mechanical modeling of the electronic transitions associated with the UV absorption spectra., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This article describes how the increased use of energy-efficient solid-state light sources (e.g., light-emitting diode [LED]-based illumination) in hospitals, pharmacies, and at home can help alleviate concerns of photodegradation for pharmaceuticals. LED light sources, unlike fluorescent ones, do not have spurious spectral contributions <400 nm. Because photostability is primarily evaluated in the International Council of Harmonization Q1B tests with older fluorescent bulb standards (International Organization for Standardization 10977), the amount of photodegradation observed can over-predict what happens in reality, as products are increasingly being stored and used in environments fitted with LED bulbs. Because photodegradation is premised on light absorption by a compound of interest (or a photosensitizer), one can use the overlap between the spectral distribution of a light source and the absorption spectra of a given compound to estimate if photodegradation is a possibility. Based on the absorption spectra of a sample of 150 pharmaceutical compounds in development, only 15% would meet the required overlap to be a candidate to undergo direct photodegradation in the presence of LED lights, against a baseline of 55% of compounds that would, when considering regular fluorescent lights. Biological drug products such as peptides and monoclonal antibodies are also expected to benefit from the use of more efficient solid-state lighting., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Radiation is the fourth most prevalent type of pollution following the water, air and noise pollution. It can adversely affect normal bodily functions. Radiation alters the protein and mRNA expression of drugmetabolizing enzymes and drug transporters and the pharmacokinetic characteristics of drugs, thereby affecting drug absorption, distribution, metabolism, and excretion. Therefore, it is important to study the pharmacokinetic changes in drugs under radiation., Methods: To update data on the effects of ionizing radiation and non-ionizing radiation caused by environmental pollution or clinical treatments on the protein and mRNA expression of drug-metabolizing enzymes and drug transporters. Data and information on pharmacokinetic changes in drugs under radiation were analyzed and summarized., Results: The effect of radiation on cytochrome P450 is still a subject of debate. The widespread belief is that higherdose radiation increased the expression of CYP1A1 and CYP1B1 of rat, zebrafish or human, CYP1A2, CYP2B1, and CYP3A1 of rat, and CYP2E1 of mouse or rat, and decreased that of rat's CYP2C11 and CYP2D1. Radiation increased the expression of multidrug resistance protein, multidrug resistance-associated protein, and breast cancer resistance protein. The metabolism of some drugs, as well as the clearance, increased during concurrent chemoradiation therapy, whereas the half-life, mean residence time, and area under the curve decreased. Changes in the expression of cytochrome P450 and drug transporters were consistent with the changes in the pharmacokinetics of some drugs under radiation., Conclusion: The findings of this review indicated that radiation caused by environmental pollution or clinical treatments can alter the pharmacokinetic characteristics of drugs. Thus, the pharmacokinetics of drugs should be rechecked and the optimal dose should be re-evaluated after radiation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Pharmaceuticals are a group of ubiquitous emerging pollutants, many of which have been shown to undergo efficient photolysis in the environment. Photochemically produced reactive intermediates (PPRIs) sensitized by the pharmaceuticals in sunlit natural waters may induce photodegradation of coexisting compounds. In this study, the roles of coexisting contaminants on the phototransformation of pharmaceuticals were unveiled with the fibrate drugs gemfibrozil (GMF), fenofibrate (FNF), and fenofibric acid (FNFA) as model compounds. GMF undergoes initial concentration dependent photodegradation due to the involvement of singlet oxygen ( 1 O 2 ) initiated self-sensitized photolysis, and undergoes pH dependent photodegradation due to dissociation and hydroxyl radical (OH) generation. The decarboxylated intermediates of GMF and coexisting FNFA significantly accelerated the photodegradation of GMF. The promotional effects of the decarboxylated intermediates are attributed to generation of PPRIs, e.g. 1 O 2 , superoxide (O 2 - ), that subsequently react with GMF. Besides, FNFA can also promote the photodegradation of GMF through the electron transfer reaction from ground state GMF to excited state FNFA, leading to the formation of decarboxylated intermediates. The formed intermediates can subsequently also facilitate GMF photodegradation. The results presented here provided valuable novel insights into the effects of coexisting contaminants on the photodegradation of pharmaceuticals in polluted waters., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Removal of pharmaceutically active compounds (PhACs) in constructed wetlands (CWs) is a complex interplay of different processes. We studied fate and distribution of seven PhACs (caffeine, CAF; naproxen, NAP; metoprolol, MET; propranolol, PRO; ibuprofen, IBP; carbamazepine, CBZ; diclofenac, DFC) in mesocosm CWs and effects of irradiation via pre-photocatalysis, substrate composition (mainly sediment) through addition of litter (dead plant biomass), and plants. CWs showed high removal of CAF, NAP, MET, PRO, and IBP (79-99%). All seven PhACs were detected in substrate and plant tissues as well as IBP intermediates. Estimated PhAC mass balance showed that sorption dominated PRO removal in CWs while other PhACs were mainly removed by biodegradation and/or phytodegradation. Pre-photocatalysis significantly increased removal of PhACs except for CAF and IBP, and decreased accumulation of PhACs in substrate and plant tissues of the following wetland compartment. Litter addition in CW significantly enhanced removal of PRO and CBZ via biodegradation and/or phytodegradation. Plants played an essential and positive role in removing PhACs, resulting from direct phytoremediation and indirectly enhancing sorption and biodegradation. Our study provides knowledge to understand removal mechanisms of PhACs in CWs and to potentially enhance PhAC removal by developing pre-photocatalysis, adding dead plant biomass, and optimizing vegetation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The electro-peroxone (E-peroxone) process is an emerging ozone-based advanced oxidation process (AOP) that has shown large potential for micropollutant abatement in water treatment. To evaluate its performance under more realistic conditions of water treatment, a continuous-flow pilot E-peroxone system was developed and compared with conventional ozonation and a UV/O 3 process for micropollutant abatements in various water matrices (groundwater, surface water, and secondary wastewater effluent) in this study. With a specific ozone dose of 1.5 mg O 3 /mg DOC, micropollutants that have high and moderate reactivity with ozone (O 3 ) (diclofenac, naproxen, gemfibrozil, and bezafibrate) could be sufficiently abated (>90% abatement) in the various waters by all three processes. However, ozone-resistant micropollutants (ibuprofen, clofibric acid, and chloramphenicol) were abated only by ∼32-68%, 68-91%, and 73-90% during conventional ozonation of the selected groundwater, surface water, and secondary wastewater effluent, respectively. By electro-generating H 2 O 2 or applying UV irradiation to enhance O 3 transformation to •OH during ozonation, the E-peroxone and UV/O 3 processes similarly enhanced the abatement efficiencies of ozone-resistant micropollutants by ∼15-43%, ∼5-15%, and ∼5-10% in the groundwater, surface water, and secondary wastewater effluent, respectively. In addition, the E-peroxone and UV/O 3 processes significantly reduced bromate formation during the treatment of the three waters compared to conventional ozonation. Due to its higher efficiency, the E-peroxone process reduced ∼10-53% of the energy consumption required to abate the concentration of chloramphenicol (the most ozone-resistant micropollutant spiked in the waters) by 1 order of magnitude in the three waters compared to conventional ozonation. In contrast, the UV/O 3 process consumed approximately 4-10 times higher energy than conventional ozonation. This pilot-scale study demonstrates that the E-peroxone process can provide a feasible, effective, and energy-efficient alternative for micropollutant abatement and bromate control in water and wastewater treatment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In this study, UV-C/H 2 O 2 and UV-C/[Formula: see text] processes as photooxidative Advanced oxidation processes were applied for the treatment of seven pharmaceuticals, either already included in the Directive 2013/39/EU "watch list" (17α- ethynylestradiol, 17β-estradiol) or with potential to be added in the near future due to environmental properties and increasing consumption (azithromycin, carbamazepine, dexamethasone, erythromycin and oxytetracycline). The influence of process parameters (pH, oxidant concentration and type) on the pharmaceuticals degradation was studied through employed response surface modelling approach. It was established that degradation obeys first-order kinetic regime regardless structural differences and over entire range of studied process parameters. The results revealed that the effectiveness of UV-C/H 2 O 2 process is highly dependent on both initial pH and oxidant concentration. It was found that UV-C/[Formula: see text] process, exhibiting several times faster degradation of studied pharmaceuticals, is less sensitive to pH changes providing practical benefit to its utilization. The influence of water matrix on degradation kinetics of studied pharmaceuticals was studied through natural organic matter effects on single component and mixture systems.

Photodegradation is one of the major pathways of the degradation of drugs. Some therapeutic agents and excipients are highly sensitive to light and undergo significant degradation, challenging the quality and the stability of the final product. The adequate knowledge of photodegradation mechanisms and kinetics of photosensitive therapeutic entities or excipients is a pivotal aspect in the product development phase. Hence, various pharmaceutical regulatory agencies, across the world, mandated the industries to assess the photodegradation of pharmaceutical products from manufacturing stage till storage, as per the guidelines given in the International Conference on Harmonization (ICH). Recently, numerous formulation and/or manufacturing strategies has been investigated for preventing the photodegradation and enhancing the photostability of photolabile components in the pharmaceutical dosage forms. The primary focus of this review is to discuss various photodegradation mechanisms, rate kinetics, and the factors that influence the rate of photodegradation. We also discuss light-induced degradation of photosensitive lipids and polymers. We conclude with a brief note on different approaches to improve the photostability of photosensitive products.

A candidate drug within the cardiovascular area was identified during early research and evaluated for further development. The aim was to understand and explain the degradation mechanisms for the present compound. The stability of the active pharmaceutical ingredient (API) in solution and solid state was studied during different conditions. The bulk compound was exposed to elevated temperatures, increased relative humidity and stressed light conditions. Degradation of the drug in solutions was followed in the presence versus absence of ethylenediaminetetraacetic acid (EDTA), during aerobic versus anaerobic conditions, stored protected from light versus exposed to light and as a function of pH and concentration. It was possible to improve the stability by adding EDTA and completely abolish degradation by storing dissolved compound at anaerobic conditions. Solutions of API were stable between pH3 and 7, with some degradation at pH1, when stored protected from light and at 22°C, but degrade rapidly when exposed to ambient light conditions. The degradation products were identified by mass spectroscopy. Degradation schemes were drawn. There was concentration dependence in the degradation of dissolved drug when exposed to light, showing a titration behavior that concurred with the measured critical micelle/aggregation concentration (CMC/CAC) of the compound. The compound was stable in solution during the investigated time period, at concentrations above CMC/CAC, where the molecule was protected from photodegradation when the compound aggregated. Below CMC/CAC, a significant degradation of the API occurred. This may be a potential explanation why other surface active compounds show concentration dependent degradation. The photosensitivity was also observed for the neutral compound in crystalline and amorphous form, as well as for the crystalline chloride salt of the drug. However, the degradation of amorphous form was faster compared to crystalline material. No difference was observed in the degradation pattern between the neutral form of the compound and the salt form of the drug., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This study investigated the i) kinetics, and ii) proportion of photolysis of 30 relatively stable active pharmaceutical ingredients (APIs) during artificial UV irradiation for 28 d in ammonium acetate buffer, filtered and unfiltered river water. Buffer was included to control removal kinetics under stable pH conditions and without particulate matter. Dark controls were used to determine removal due to other processes than photolysis and calculate the proportion of photolysis of the total removal. The removal of each API in each matrix was determined using online solid phase extraction/liquid chromatography tandem mass spectrometry (online SPE/LC-MS/MS). Most APIs transformed during the 28 d of UV irradiation and the dark controls showed that photolysis was the major removal process for the majority of the APIs studied. The half-lives ranged from 6 h (amitriptyline) in unfiltered river water to 884 h (37 d, carbamazepine) in buffer. In unfiltered river water, the proportion of APIs with short half-lives (<48 h) was much higher (29%) than in the other matrices (4%), probably due to additional organic carbon, which could have promoted indirect photolysis. Furthermore, two APIs, memantine and fluconazole, were stable in all three matrices, while alprazolam was stable in buffer and unfiltered river water and four additional APIs were stable in buffer. Considering the relatively long-term UV-exposure, this study enabled the investigation of environmentally relevant half-lives in natural waters. Many APIs showed high persistence, which is environmentally concerning and emphasizes the importance of further studies on their environmental fate and effects., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

To upkeep health of astronauts in a unique, isolated, and extreme environment of space is the primary goal for a successful space mission, hence, safe and efficacious medications are essential for the wellness of astronauts. Space medication has been challenged with problems related to efficacy. Along with altered physiology, one of the possible reasons could be instability of space medications in the presence of harsh spaceflight environmental conditions. Altered physical and chemical stability can result in reduced potency which can result in reduced efficacy. Right now, medicines from the International Space Station are replaced before their expiration. But, for longer duration missions to Mars or any other asteroid, there will not be any chance of replacement of medicines. Hence, it is desired that medicines maintain the shelf-life throughout the space mission. Stability of medicines used for short term or long term space missions cannot be judged by drug stability guidelines based on terrestrial environmental factors. Unique environmental conditions related to spaceflight include microgravity, excessive vibration, hard vacuum, humidity variation, temperature differences and excessive radiation, which may cause instability of medicines. This write-up provides a review of the problem and countermeasure approaches for pharmaceuticals exposed to the space environment. The first part of the article discusses thought processes behind outlining of International Conference on Harmonization drug stability guidelines, Q1A (R2) and Q1B, and its acceptance limits for accelerated stability study. The second part of the article describes the difference in the radiation environment of deep space compared to radiation environment inside the space shuttle based on penetration power of different types of radiation. In the third part of the article, various promising approaches are listed which can be used for assurance of space medicine stability. One of the approaches is the use of ground-based space simulation analogues and statistical treatment to data to calculate failure rate of drugs and probabilistic risk assessment. Another approach is to innovate storage and packaging technology using radiation harden polymer or using cryogenic temperatures., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Affinity purification is one of the most prevalent methods for the target identification of small molecules. Preparation of an appropriate chemical for immobilization, however, is a tedious and time-consuming process. A decade ago, a photoreaction method for generating affinity beads was reported, where compounds are mixed with agarose beads carrying a photoreactive group (aryldiazirine) and then irradiated with ultraviolet light under dry conditions to form covalent attachment. Although the method has proven useful for identifying drug targets, the beads suffer from inefficient ligand incorporation and tend to shrink and aggregate, which can cause nonspecific binding and low reproducibility. We therefore decided to craft affinity beads free from these shortcomings without compromising the ease of preparation. We herein report a modified method; first, a compound of interest is mixed with a crosslinker having an activated ester and a photoreactive moiety on each end. This mixture is then dried in a glass tube and irradiated with ultraviolet light. Finally, the conjugates are dissolved and reacted with agarose beads with a primary amine. This protocol enabled us to immobilize compounds more efficiently (approximately 500-fold per bead compared to the original method) and generated beads without physical deterioration. We herein demonstrated that the new FK506-immobilized beads specifically isolated more FKBP12 than the original beads, thereby proving our method to be applicable to target identification experiments., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Iodinated pharmaceuticals, thyroxine (a thyroid hormone) and diatrizoate (an iodinated X-ray contrast medium), are among the most prescribed active pharmaceutical ingredients. Both of them have been reported to potentially disrupt thyroid homeostasis even at very low concentrations. In this study, UV-254 nm-based photolysis and photochemical processes, i.e., UV only, UV/H 2 O 2 , and UV/S 2 O 8 2- , were evaluated for the destruction of these two pharmaceuticals. Approximately 40% of 0.5μM thyroxine or diatrizoate was degraded through direct photolysis at UV fluence of 160mJcm -2 , probably resulting from the photosensitive cleavage of C-I bonds. While the addition of H 2 O 2 only accelerated the degradation efficiency to a low degree, the destruction rates of both chemicals were significantly enhanced in the UV/S 2 O 8 2- system, suggesting the potential vulnerability of the iodinated chemicals toward UV/S 2 O 8 2- treatment. Such efficient destruction also occurred in the presence of radical scavengers when biologically treated wastewater samples were used as reaction matrices. The effects of initial oxidant concentrations, solution pH, as well as the presence of natural organic matter (humic acid or fulvic acid) and alkalinity were also investigated in this study. These results provide insights for the removal of iodinated pharmaceuticals in water and/or wastewater using UV-based photochemical processes., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The susceptibility for photon-induced degradation of over 800 pharmaceutical compounds present in the LOPAC 1280 library, was analyzed by UV/Vis spectroscopy in the absence or presence of TiO 2 P25 in water. In general, few compounds were effectively degraded in the absence of the TiO 2 photocatalyst (3% of all compounds tested), while in the presence of TiO 2 , the majority of compounds was converted, often to a large degree. Differences in degree of degradation are evaluated on the basis of molecular weight, as well as the chemical nature of the drug compounds (functional groups and pharmacological classes). In general, if the molecular weight increases, the degradation efficacy decreases. Relatively high degrees of conversion can be achieved for (relatively small) molecules with functional groups such as aldehydes, alcohols, ketones and nitriles. A low degree of conversion was observed for compounds composed of conjugated aromatic systems. Trends in degradation efficacy on the basis of pharmacological class, e.g. comparing hormones and opioids, are not obvious., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The selection and prioritization of pharmaceuticals and their transformation products for evaluating effects on the environment and human health is a challenging task. One common approach is based on compounds (e.g., mixture composition, concentrations), and another on biology (e.g., relevant endpoint, biological organizational level). Both of these approaches often resemble a Lernaean Hydra-they can create more questions than answers. The present study embraces this complexity, providing an integrated approach toward assessing the potential effects of transformation products of pharmaceuticals by means of mutagenicity, estrogenicity, and differences in the gene expression profiles. Mutagenicity using the tk kinase assay was applied to assess a list of 11 priority pharmaceuticals, namely, atenolol, azithromycin, carbamazepine, diclofenac, ibuprofen, erythromycin, metoprolol, ofloxacin, propranolol, sulfamethoxazole, and trimethoprim. The most mutagenic compounds were found to be β-blockers. In parallel, the photolabile pharmaceuticals were assessed for their mixture effects on mutagenicity (tk assay), estrogenicity (T47D- KBluc assay), and gene expression (microarrays). Interestingly, the mixtures were mutagenic at the µg/L level, indicating a synergistic effect. None of the photolysed mixtures were statistically significantly estrogenic. Gene expression profiling revealed effects related mainly to certain pathways, those of the p53 gene, mitogen-activated protein kinase, alanine, aspartate, and glutamate metabolism, and translation-related (spliceosome). Fourteen phototransformation products are proposed based on the m/z values found through ultra-performance liquid chromatography-tandem mass spectrometry analysis. The transformation routes of the photolysed mixtures indicate a strong similarity with those obtained for each pharmaceutical separately. This finding reinforces the view that transformation products are to be expected in naturally occurring mixtures. Environ Toxicol Chem 2016;35:2753-2764. © 2016 SETAC., (© 2016 SETAC.)

Aim: A procedure was developed for the assessment of photochemical stability of drugs in blood and plasma under standardized conditions. The procedure avoids a variable outcome of photochemical stability experiments and tests relevant worst case conditions so that unnecessary light protection is avoided. Results/methodology: Blood and plasma were spiked with a mixture of drugs and incubated in a Suntest CPS(+), in the laboratory on the bench and near the window on a sunny summer day. The results were compared., Discussion/conclusion: No protection from light, limited protection from light and full protection from light are advised for drugs that are stable in plasma in the Suntest CPS(+) at 250 W/m(2) for at least 30 min, for 5-30 min and for <5 min, respectively.

An industrial wastewater effluent coming from a pharmaceutical laboratory has been treated in a semi-industrial autonomous solar compound parabolic collector (CPC) plant. A photo-Fenton process assisted with ferrioxalate has been used. Up to 79% of TOC can be removed in 2 h depending on initial conditions when treating an aqueous effluent containing up to 400 ppm of initial organic carbon concentration (TOC). An initial ratio of Fe(II)/TOC higher than 0.5 guarantees a high removal. It can be seen that most of TOC removal occurs early in the first hour of reaction. After this time, mineralization was very slow, although H2O2 was still present in solution. Indeed it decomposed to form oxygen in inefficient reactions. It is clear that remaining TOC was mainly due to the presence of acetates which are difficult to degrade., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Micropollutant removal in an algal treatment system fed with source separated wastewater streams was studied. Batch experiments with the microalgae Chlorella sorokiniana grown on urine, anaerobically treated black water and synthetic urine were performed to assess the removal of six spiked pharmaceuticals (diclofenac, ibuprofen, paracetamol, metoprolol, carbamazepine and trimethoprim). Additionally, incorporation of these pharmaceuticals and three estrogens (estrone, 17β-estradiol and ethinylestradiol) into algal biomass was studied. Biodegradation and photolysis led to 60-100% removal of diclofenac, ibuprofen, paracetamol and metoprolol. Removal of carbamazepine and trimethoprim was incomplete and did not exceed 30% and 60%, respectively. Sorption to algal biomass accounted for less than 20% of the micropollutant removal. Furthermore, the presence of micropollutants did not inhibit C. sorokiniana growth at applied concentrations. Algal treatment systems allow simultaneous removal of micropollutants and recovery of nutrients from source separated wastewater. Nutrient rich algal biomass can be harvested and applied as fertilizer in agriculture, as lower input of micropollutants to soil is achieved when algal biomass is applied as fertilizer instead of urine., (Copyright © 2015 Elsevier B.V. All rights reserved.)

To evaluate the performance of zeolite-supported carbon-doped TiO(2) composite catalysts toward target pollutants under solar light irradiation, the adsorption and photocatalytic degradation of 18 pharmaceuticals and pesticides with distinguishing features (molecular size and volume, and photolysis) were investigated using mordenite zeolites with SiO(2)/Al(2)O(3) ratios of 18 and 240. Different quantities of carbon-doped TiO(2) were coated on the zeolites, and then the finished composite catalysts were tested in demineralized, surface, and hospital wastewater samples, respectively. The composite photocatalysts were characterized by X-ray diffraction, field emission scanning electron microscopy, and surface area and porosity analyses. Results showed that a dispersed layer of carbon-doped TiO(2) is formed on the zeolite surface; this layer blocks the micropores of zeolites and reduces their surface area. However, these reductions did not significantly affect adsorption onto the zeolites. Our results demonstrated that zeolite-supported carbon-doped TiO(2) systems can effectively degrade 18 pharmaceuticals and pesticides in demineralized water under natural and simulated solar light irradiation. In surface and hospital wastewaters, zeolite-supported carbon-doped TiO(2) systems present excellent anti-interference capability against radical scavengers and competitive organics for pollutants removal, and higher pollutants adsorption on zeolites evidently enhances the removal rate of target pollutants in surface and hospital wastewater samples with a complicated matrix.

Hospital effluents are an important source of residual drugs and other classes of pharmaceuticals in aquatic environments. The raw wastewater from the studied hospital exhibited acute toxicity to vertebrate organisms, and Cyprinus carpio was the most sensitive organism tested. A mixture of 19 commonly used pharmaceuticals caused acute toxicity to C. carpio with an LC50 value of 60.68mgL(-1) after 96h. This study demonstrated that irradiation for 1-5days significantly increased the acute toxicity of the pharmaceuticals to fish, leading to increased mortality after a 2-h exposure and approximately 40% of the surviving fish died within 28days. The pre-irradiated pharmaceutical mixture also induced strange behaviors in the fish that survived the test. The synergistic increase in toxicity caused by the photolysis and mixing of pharmaceuticals cannot be ignored and warrants further examination., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In search of new options to achieve removal of pharmaceuticals in the environment, combined ultrasound and ozonation has become a focus of intense investigation for wastewater treatment. In this study, three pharmaceuticals were selected as model compounds for degradation experiments: diclofenac (DCF), sulfamethoxazole (SMX) and carbamazepine (CBZ). Comparison of the degradation rates for both ozonation and combined ultrasound/ozonation treatments was performed on single synthetic solutions as well as on a mixture of the selected pharmaceuticals, under different experimental conditions. For single synthetic solutions, the efficiency removal for ozonation reached 73%, 51% and 59% after 40 min for DCF, SMX and CBZ, respectively. Comparable results were obtained for pharmaceuticals in mixture. However, the combined ultrasound/ozone treatment was found to increase degradation efficiencies for both DCF and SMX single solutions up to 94% and 61%, respectively, whereas lower removal yields, up to 56%, was noted for CBZ. Likewise, when the combined treatment was applied to the mixture, relatively low removal efficiencies was found for CBZ (44%) and 90% degradation yield was achieved for DCF.

UV/H2O2 treatment is a well-established technique to degrade organic micropollutants. A CFD model in combination with an advanced kinetic model is presented to predict the degradation of organic micropollutants in UV (LP)/H2O2 reactors, accounting for the hydraulics, fluence rate, complex (photo)chemical reactions in the water matrix and the interactions between these processes. The model incorporates compound degradation by means of direct UV photolysis, OH radical and carbonate radical reactions. Measurements of pharmaceutical degradations in pilot-scale UV/H2O2 reactors are presented under different operating conditions. A comparison between measured and modeled degradation for a group of 35 pharmaceuticals resulted in good model predictions for most of the compounds. The research also shows that the degradation of organic micropollutants can be dependent on temperature, which is relevant for full-scale installations that are operated at different temperatures over the year., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

To minimize environmental pharmaceutical micropollutants, treatment of human urine could be an efficient approach due to the high pharmaceutical concentration and toxic potential excreted in urine. This study investigated the degradation kinetics and mechanisms of sulfamethoxazole (SMX), trimethoprim (TMP) and N4-acetyl-sulfamethoxazole (acetyl-SMX) in synthetic fresh and hydrolyzed human urines by low-pressure UV, and UV combined with H2O2 and peroxydisulfate (PDS). The objective was to compare the two advanced oxidation processes (AOPs) and assess the impact of urine matrices. All three compounds reacted quickly in the AOPs, exhibiting rate constants of (6.09-8.53) × 10(9) M(-1)·s(-1) with hydroxyl radical, and (2.35-16.1) × 10(9) M(-1)·s(-1) with sulfate radical. In fresh urine matrix, the pharmaceuticals' indirect photolysis was significantly suppressed by the scavenging effect of urine citrate and urea. In hydrolyzed urine matrix, the indirect photolysis was strongly affected by inorganic urine constituents. Chloride had no apparent impact on UV/H2O2, but significantly raised the hydroxyl radical concentration in UV/PDS. Carbonate species reacted with hydroxyl or sulfate radical to generate carbonate radical, which degraded SMX and TMP, primarily due to the presence of aromatic amino group(s) (k = 2.68 × 10(8) and 3.45 × 10(7) M(-1)·s(-1)) but reacted slowly with acetyl-SMX. Ammonia reacted with hydroxyl or sulfate radical to generate reactive nitrogen species that could react appreciably only with SMX. Kinetic simulation of radical concentrations, along with products analysis, helped elucidate the major reactive species in the pharmaceuticals' degradation. Overall, the AOPs' performance was higher in the hydrolyzed urine than fresh urine matrix with UV/PDS better than UV/H2O2, and varied significantly depending on pharmaceutical's structure.

In view of the inefficient elimination of micro-pollutants by today's conventional biological treatments and new legislation requiring elimination of at least 80 % of their concentration, the application of an advanced tertiary treatment must be studied. A good option would be advanced oxidation processes (AOPs), which have very often been combined with physicochemical pre-treatSments to increase efficiency or reduce operating costs. This study focused on the combination of membrane nanofiltration and solar photo-Fenton for the main purpose of removing five pharmaceuticals (sulfamethoxazole, ibuprofen, ofloxacin, carbamazepine and flumequine) from real MWTP effluents under realistic conditions (μg L(-1)). This research also included tests performed with modified photo-Fenton using a low iron concentration at circumneutral pH and a low hydrogen peroxide dose, in an attempt to reduce major treatment costs. Over 80 % of dissolved organic carbon, chemical oxygen demand and turbidity were also retained during nanofiltration, making pharmaceutical removal less efficient in terms of concentrate treatment time than direct treatment, i.e. the concentrate illumination time was around 150 min while direct treatment was around 40 min. Nevertheless, it should be highlighted that, although no savings in installation costs was observed for the combined system (nanofiltration/solar photo-Fenton), the reaction rate improved and so, there was a savings in reagent costs (mainly hydrogen peroxide and sulfuric acid).

In recent years, membrane technologies (nanofiltration (NF)/reverse osmosis (RO)) have received much attention for micropollutant separation from Municipal Wastewater Treatment Plant (MWTP) effluents. Practically all micropollutants are retained in the concentrate stream, which must be treated. Advanced Oxidation Processes (AOPs) have been demonstrated to be a good option for the removal of microcontaminants from water systems. However, these processes are expensive, and therefore, are usually combined with other techniques (such as membrane systems) in an attempt at cost reduction. One of the main costs in solar photo-Fenton comes from reagent consumption, mainly hydrogen peroxide and chemicals for pH adjustment. Thus, in this study, solar photo-Fenton was used to treat a real MWTP effluent with low initial iron (less than 0.2 mM) and hydrogen peroxide (less than 2 mM) concentrations. In order to work at neutral pH, iron complexing agents (EDDS and citrate) were used in the two cases studied: direct treatment of the MWTP effluent and treatment of the concentrate stream generated by NF. The degradation of five pharmaceuticals (carbamazepine, flumequine, ibuprofen, ofloxacin and sulfamethoxazole) spiked in the effluent at low initial concentrations (μg L(-1)) was monitored as the main variable in the pilot-plant-scale photo-Fenton experiments. In both effluents, pharmaceuticals were efficiently removed (>90%), requiring low accumulated solar energy (2 kJUV L(-1), key parameter in scaling up the CPC photoreactor) and low iron and hydrogen peroxide concentrations (reagent costs, 0.1 and 1.5 mM, respectively). NF provided a clean effluent, and the concentrate was positively treated by solar photo-Fenton with no significant differences between the direct MWTP effluent and NF concentrate treatments., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Drug sterilization with ionizing radiation is a well-established technology and is gaining ground the last decades due to its numerous advantages. Identification of irradiated drugs would be interesting and, in this respect, the present work aims, for the first time to the authors' best knowledge, to explore whether OSL and TL can be employed as methods for post-sterilization dosimetry on commercial drugs, i.e., as tools for the detection of irradiated drugs. Five widely used drugs, i.e., Daktarin(®), Aspirin(®), Panadol(®), Brufen(®) and Procef(®), are used for this purpose. Preliminary findings are very promising towards the post-sterilization dosimetry and the use of commercial drugs for normal and/or accidental dosimetry., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Drug photodegradation data are usually treated by zero-, first- or second-order kinetic equations. Such treatments would lack reliability since the aforementioned equations have been originally developed for pure thermal reactions. In this respect, it has recently been shown that unimolecular photodegradations obey Ф-order kinetics (Maafi and Maafi, 2013). However, no similar information is, thus far, available for other reactions including photoreversible AB(2Ф) systems. This paper aims at filling this gap for AB(2Ф) kinetics., Methods: Runge-Kutta numerical integration data for photoreversible reactions traces were combined with a template equation in order to derive an optimized (semi-empirical) integrated rate-law equation for AB(2Ф) reactions. The proposed model equation was test by examining its ability to fit synthetic Runge-Kutta data that have not been used for the optimization. The obtained fitting parameters are then compared to their theoretical counterparts., Results: Both an integrated rate-law and an analytical equation for the overall reaction rate-constant were set for photoreversible drug reactions. The values of overall reaction rate-constant and initial velocity obtained theoretically correlated well with those obtained by fitting the kinetic traces of reactions with the derived integrated rate-law. AB(2Ф) photodegradation reactions have been proven to obey Ф-order kinetics. The equation proposed describes faithfully their kinetic behaviour in solution. The formula of the overall rate-constant involves both reagents' characteristics and experimental parameters. These equations facilitated the rationalisation and prediction of the individual effects of each reaction parameter. Specially, our results proved a self-photostabilisation with increasing initial drug-concentration and demonstrated the potential for actinometry of drugs obeying AB(2Ф) mechanism., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Sterilization by gamma irradiation has shown a strong applicability for a wide range of pharmaceutical products. Due to the requirement for terminal sterilization where possible in the pharmaceutical industry, gamma sterilization has proven itself to be an effective method as indicated by its acceptance in the European Pharmacopeia and the United States Pharmacopeia ( ). Some of the advantages of gamma over competitive procedures include high penetration power, isothermal character (small temperature rise), and no residues. It also provides a better assurance of product sterility than aseptic processing, as well as lower validation demands. Gamma irradiation is capable of killing microorganisms by breaking their chemical bonds, producing free radicals that attack the nucleic acid of the microorganism. Sterility by gamma irradiation is achieved mainly by the alteration of nucleic acid and preventing the cellular division. This review focuses on the extensive application of gamma sterilization to a wide range of pharmaceutical components including active pharmaceutical ingredients, excipients, final drug products, and combination drug-medical devices. A summary of the published literature for each class of pharmaceutical compound or product is presented. The irradiation conditions and various quality control characterization methodologies that were used to determine final product quality are included, in addition to a summary of the investigational outcomes. Based on this extensive literature review and in combination with regulatory guidelines and other published best practices, a decision tree for implementation of gamma irradiation for pharmaceutical products is established. This flow chart further facilitates the implementation of gamma irradiation in the pharmaceutical development process. The summary therefore provides a useful reference to the application and versatility of gamma irradiation for pharmaceutical sterilization., Lay Abstract: Many pharmaceutical products require sterilization to ensure their safe and effective use. Sterility is therefore a critical quality attribute and is essential for direct injection products. Due to the requirement for terminal sterilization, where possible in the pharmaceutical industry sterilization by gamma irradiation has been commonly used as an effective method to sterilize pharmaceutical products as indicated by its acceptance in the European Pharmacopeia. Gamma sterilization is a very attractive terminal sterilization method in view of its ability to attain 10(-6) probability of microbial survival without excessive heating of the product or exposure to toxic chemicals. However, radiation compatibility of a product is one of the first aspects to evaluate when considering gamma sterilization. Gamma radiation consists of high-energy photons that result in the generation of free radicals and the subsequent ionization of chemical bonds, leading to cleavage of DNA in microorganisms and their subsequent inactivation. This can result in a loss of active pharmaceutical ingredient potency, the creation of radiolysis by-products, a reduction of the molecular weight of polymer excipients, and influence drug release from the final product. There are several strategies for mitigating degradation effects, including optimization of the irradiation dose and conditions. This review will serve to highlight the extensive application of gamma sterilization to a broad spectrum of pharmaceutical components including active pharmaceutical ingredients, excipients, final drug products, and combination drug-medical devices.

Advanced wastewater treatment is necessary to effectively remove emerging contaminants (ECs) with chronic toxicity, endocrine disrupting effects, and the capability to induce the proliferation of highly resistant microbial strains in the environment from before wastewater disposal or reuse. This paper investigates the efficiency of a novel hybrid process that applies membrane ultrafiltration, activated carbon adsorption, and ultrasound irradiation simultaneously to remove ECs. Diclofenac, carbamazepine, and amoxicillin are chosen for this investigation because of their assessed significant environmental risks. Removal mechanisms and enhancement effects are analysed in single and combined processes. The influence of adsorbent dose and ultrasonic frequency to EC removal are also investigated. Results suggest that adsorption is probably the main removal mechanism and is affected by the nature of ECs and the presence of other components in the mixture. Almost complete removals are achieved in the hybrid process for all ECs., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Boron-doped diamond (BDD) is playing an important role in environmental electrochemistry and has been successfully applied to the degradation of various bio-refractory organic pollutants. However, the review concerning recent progress in this research area is still very limited. This mini-review updated recent advances on the removal of three kinds of bio-refractory wastewaters including pharmaceuticals, pesticides, and dyes using BDD electrode. It summarized the important parameters in three electrochemical oxidation processes, i.e., anodic oxidation (AO), electro-Fenton (EF), and photoelectro-Fenton (PEF) and compared their different degradation mechanisms and behaviors. As an attractive improvement of PEF, solar photoelectro-Fenton using sunlight as UV/vis source presented cost-effectiveness, in which the energy consumption for enrofloxacin removal was 0.246 kWh/(g TOC), which was much lower than that of 0.743 and 0.467 kWh/(g TOC) by AO and EF under similar conditions. Finally the existing problems and future prospects in research were suggested.

A reactive oxygen species (ROS) assay was previously developed for photosafety evaluation of pharmaceuticals, and the present multi-center study aimed to establish and validate a standard protocol for ROS assay. In three participating laboratories, two standards and 42 coded chemicals, including 23 phototoxins and 19 nonphototoxic drugs/chemicals, were assessed by the ROS assay according to the standardized protocol. Most phototoxins tended to generate singlet oxygen and/or superoxide under UV-vis exposure, but nonphototoxic chemicals were less photoreactive. In the ROS assay on quinine (200 µm), a typical phototoxic drug, the intra- and inter-day precisions (coefficient of variation; CV) were found to be 1.5-7.4% and 1.7-9.3%, respectively. The inter-laboratory CV for quinine averaged 15.4% for singlet oxygen and 17.0% for superoxide. The ROS assay on 42 coded chemicals (200 µm) provided no false negative predictions upon previously defined criteria as compared with the in vitro/in vivo phototoxicity, although several false positives appeared. Outcomes from the validation study were indicative of satisfactory transferability, intra- and inter-laboratory variability, and predictive capacity of the ROS assay., (Copyright © 2012 John Wiley & Sons, Ltd.)

Oxidation of aromatic compounds of phenolic (paracetamol, beta-oestradiol and salicylic acid) and carboxylic (indomethacin and ibuprofen) structure used in pharmaceutics was studied. Aqueous solutions were treated with pulsed corona discharge (PCD) as a means for advanced oxidation. Pulse repetition frequency, delivered energy dose and oxidation media were the main parameters studied for their influence on the process energy efficiency. The PCD treatment appeared to be effective in oxidation of the target compounds: complete degradation of pollutant together with partial mineralization was achieved at moderate energy consumption; oxidation proceeds faster in alkaline media. Low-molecular carboxylic acids were identified as ultimate oxidation by-products formed in the reaction.

In order to investigate the effect of sunlight on the persistence and ecotoxicity of pharmaceuticals contaminating the aquatic environment, we exposed nine pharmaceuticals (acetaminophen (AA), amiodarone (AM), dapsone (DP), dexamethasone (DX), indomethacin (IM), naproxen (NP), phenytoin (PH), raloxifene (RL), and sulindac (SL)) in aqueous media to sunlight and to ultraviolet (UV) irradiation at 254, 302 or 365 nm (UV-C, UV-B or UV-A, respectively). Degradation of the pharmaceuticals was monitored by means of high-performance liquid chromatography (HPLC). Sunlight completely degraded AM, DP and DX within 6 hr, and partly degraded the other pharmaceuticals, except AA and PH, which were not degraded. Similar results were obtained with UV-B, while UV-A was less effective (both UV-A and -B are components of sunlight). All the pharmaceuticals were photodegraded by UV-C, which is used for sterilization in sewage treatment plants. Thus, the photodegradation rates of pharmaceuticals are dependent on both chemical structure and the wavelength of UV exposure. Toxicity assay using the luminescent bacteria test (ISO11348) indicated that UV irradiation reduced the toxicity of some pharmaceuticals to aquatic organisms by decreasing their amount (photodegradation) and increased the toxicity of others by generating toxic photoproduct(s). These results indicate the importance of investigating not only parent compounds, but also photoproducts in the risk assessment of pharmaceuticals in aquatic environments.

UV irradiation technology as a membrane bioreactor (MBR) post-treatment was investigated and assessed. Both UV low pressure (LP) and medium pressure (MP) lamps were examined. The technology was installed in a pilot plant treating hospital wastewater to provide the study with adequate field data. The effect of the UV irradiation was enhanced with varying dosages of H2O2 to establish an advanced oxidation process (AOP). The efficiency of the pharmaceutical removal process was assessed by examining 14 micropollutants (antibiotics, analgesics, anticonvulsants, beta-blockers, cytostatics and X-ray contrast media) which are typically released by hospitals and detected with liquid chromatography coupled tandem mass spectrometry (LC-MS/MS). While the MBR treatment generally showed only a low degradation capacity for persistent pharmaceuticals, much better degradation was obtained by applying UV irradiation and H2O2 as AOP. The "conventional" cost-benefit analysis of the different technology options taking into account both electrical energy consumption and pharmaceutical removal efficiency, revealed clearly better performance of low pressure UV lamps as AOP. However, a holistic comparison between the different scenarios was carried out by evaluating their environmental impacts using the life cycle assessment (LCA) methodology. Decisive advantages were highlighted to include this approach in the decision making process., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The Radio Frequency Identification (RFID) technology promises to improve several processes in the healthcare scenario, especially those related to traceability of people and things. Unfortunately, there are still some barriers limiting the large-scale deployment of these innovative technologies in the healthcare field. Among these, the evaluation of potential thermal and non-thermal effects due to the exposure of biopharmaceutical products to electromagnetic fields is very challenging, but still slightly investigated. This paper aims to setup a controlled RF exposure environment, in order to reproduce a worst-case exposure of pharmaceutical products to the electromagnetic fields generated by the UHF RFID devices placed along the supply chain. Radiated powers several times higher than recommended by current normative limits were applied (10 W and 20 W). The electric field strength at the exposed sample location, used in tests, was as high as 100 V/m. Non-thermal effects were evaluated by chromatography techniques and in vitro assays. The results obtained for a particular case study, the ActrapidTM human insulin preparation, showed temperature increases lower than 0.5 °C and no significant changes in the structure and performance of the considered drug.

We describe a new temperature and electric field dual-stimulus responsive nanoparticle system for programmed drug delivery. Nanoparticles of a conducting polymer (polypyrrole) are loaded with therapeutic pharmaceuticals and are subcutaneously localized in vivo with the assistance of a temperature-sensitive hydrogel (PLGA-PEG-PLGA). We have shown that drug release from the conductive nanoparticles is controlled by the application of a weak, external DC electric field. This approach represents a novel interactive drug delivery system that can show an externally tailored release profile with an excellent spatial, temporal, and dosage control., (© 2011 American Chemical Society)

A mixture of five commonly used pharmaceuticals and personal care products (PPCPs) was degraded using a new combined catalyst under visible light irradiation. Scanning electron microscopy and X-ray diffraction analysis revealed that the combined catalyst was composed of copper-plating iron doped Cu2O (FeCu/Cu2O). Compared with the Fe/C inner micro-circuit, the electric currents flowing between Cu and Fe increase the speed of anodic Fe dissolution. Moreover, due to the photochemical properties, Cu2O can accelerate the PPCPs degradation processes under the irradiation of visible light. In addition, shaking increased the dissolved oxygen concentration in the solution, which not only preconditioned the photo-catalysis reaction, but also set the stage for Fe reduction. According to the experimental results, we propose the possible reaction mechanism of the reaction.

The objective of this study was to investigate if coexisting compounds could affect the fate of pharmaceuticals in surface water under solar irradiation. The degradation of metronidazole (MET) in the presence of different coexisting pharmaceuticals was investigated in batch experiments with exposure to sunlight. Tinidazole, which has a similar structure to MET, was employed as an analogue. The results indicated that the presence of an analogue with a similar photosensitive group to MET could inhibit the photodegradation of MET. In addition, the effect of coexisting pharmaceuticals with different absorption spectra on the degradation of MET was investigated. The results showed that the effect depended on the degree of overlapping absorption spectra between MET and the coexisting pharmaceuticals. The relationship between the degree of the influence and the ultraviolet absorption spectra of coexisting pharmaceuticals found in this study could give guidance in assessing the fate of pharmaceuticals in environmental water.

Benzodiazepines are widely consumed psychiatric pharmaceuticals which are frequently detected in the environment. The environmental persistence and fate of these pharmaceuticals as well as their degradation products is of high relevance and it is, yet, scarcely elucidated. In this study, the relevance of photodegradation processes on the environmental persistence of four benzodiazepines (oxazepam, diazepam, lorazepam and alprazolam) was investigated. Benzodiazepines were irradiated under simulated solar irradiation and direct and indirect (together with three different fractions of humic substances) photodegradation kinetics were determined. Lorazepam was shown to be quickly photodegradated by direct solar radiation, with a half-life time lower than one summer sunny day. On the contrary, oxazepam, diazepam and alprazolam showed to be highly resistant to photodegradation with half-life times of 4, 7 and 228 summer sunny days, respectively. Apparent indirect and direct photodegradation rates are of the same order of magnitude. However, humic acids were consistently responsible for a decrease in the photodegradation rates while fulvic acids and XAD4 fraction caused an enhancement of the photodegradation. Overall, the results highlight that photodegradation might not be an efficient pathway to prevent the aquatic environmental accumulation of oxazepam, diazepam and alprazolam. Also, nineteen direct photodegradation products were identified by electrospray mass spectrometry, the majority of which are newly identified photoproducts. This identification is crucial to a more complete understanding of the environmental impact of benzodiazepines in aquatic systems., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The effect of storage in space on the stability of vitamin B complex in two commercial vitamin tablets was examined. Multiple vitamin samples returned after storage on the space shuttle and International Space Station (ISS) along with two ground control and three positive control groups were included in the study. Content of vitamin B(3) in the tablets and in vitro dissolution rate were determined using a modified high performance liquid chromatographic assay from USP/NF 2010. Results indicate that vitamin B(3) in one of the brands tested (#2) may be subject to marginal degradation after storage on ISS for 4 months as indicated by the chromatograms for all six tablets showing a split peak appearing as a notch at the peak tip. Chromatograms were not different for ground and flight samples for Brand #1 suggesting that this may be more suitable for use in space., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objectives: Identify the photosensitive drugs included in the hospital pharmacotherapeutic guide and search for stability data on the storage, reconstitution, and dilution of these compounds., Methods: The data were obtained by referencing technical specifications, information provided by drug laboratories, and in some cases, we performed a more extensive bibliographic search (tertiary sources and conference lectures) for each particular medication. We also performed a data search on the PubMed information database (from 2004 to 2009). The drugs were placed in alphabetical order by brand since the stability of each drug when exposed to light does not depend exclusively on the primary active ingredient. Eight columns describe the principal characteristics of the drugs: brand name, active ingredient, laboratory, storage, reconstitution and dilution conditions, observations, and references., Results: The listing was comprised of 139 photosensitive medicines, of the 1,954 included in the pharmacotherapeutical guide (table 1)., Conclusions: The lack of studies published on the stability of photosensitive medications provided the need for an internal review at our hospital. It is important for drug-producing laboratories to perform photo-sensitivity tests on their products, with the results presented in the technical specifications in order to provide more accessible and reliable information. We believe that this should be required by law., (Copyright © 2010 SEFH. Published by Elsevier Espana. All rights reserved.)

Efficacy and safety of medications used for the treatment of astronauts in space may be compromised by altered stability in space. We compared physical and chemical changes with time in 35 formulations contained in identical pharmaceutical kits stowed on the International Space Station (ISS) and on Earth. Active pharmaceutical content (API) was determined by ultra- and high-performance liquid chromatography after returning to Earth. After stowage for 28 months in space, six medications aboard the ISS and two of matching ground controls exhibited changes in physical variables; nine medications from the ISS and 17 from the ground met the United States Pharmacopeia (USP) acceptance criteria for API content after 28 months of storage. A higher percentage of medications from each flight kit had lower API content than the respective ground controls. The number of medications failing API requirement increased as a function of time in space, independent of expiration date. The rate of degradation was faster in space than on the ground for many of the medications, and most solid dosage forms met USP standard for dissolution after storage in space. Cumulative radiation dose was higher and increased with time in space, whereas temperature and humidity remained similar to those on the ground. Exposure to the chronic low dose of ionizing radiation aboard the spacecraft as well as repackaging of solid dosage forms in flight-specific dispensers may adversely affect stability of pharmaceuticals. Characterization of degradation profiles of unstable formulations and identification of chemical attributes of stability in space analog environments on Earth will facilitate development of space-hardy medications.

Highly entangled TiO(2) nanowires were directly synthesized by hydrothermal growth on Ti substrates at 180 °C utilizing various organic solvents to oxidize Ti. The growth mechanism, microstructure and phase transition of TiO(2) nanowire membranes were investigated in detail. TiO(2) nanowires, with diameters of 10-20 nm and lengths up to 100 μm, show a phase transition from Type-B to anatase by annealing at 700 °C. Robust, free standing TiO(2) nanowire membranes with millimeter level thickness can be cleaved from Ti substrates or directly prepared from thin Ti foils. These porous TiO(2) membranes, while effective for mechanical microfiltration, can also photocatalytically degrade pharmaceuticals such as trimethoprim under UV irradiation., (Copyright © 2011 Elsevier B.V. All rights reserved.)

During the inter-war years, the word "radiated" did not only suggest radioactivity, but it was also used to indicate exposure to others radiations, such as ultraviolets. The actinotherapy, a new therapy in vogue, was applied to many pathologies and tried on many substances. "Radiated drugs" result of those experimentations. Their therapeutical characteristics were found during searches on rickets. Our study relates the story of fight against rickets in France, from the use of cod liver oil to the synthesis of Vitamine D.

This contribution reviews recent applications of micromanipulation, by UV photons, in DNA repair and ageing research as well as in the evaluation of the phototoxicity of drugs. In some cases, micromanipulation is combined with the comet assay, a technique, which allows a direct view on DNA damages. It is shown that, in humans, the sensitivity of DNA to UV induced damage and its subsequent repair is surprisingly stable up to high age and that drugs which are usually non-toxic induce DNA damage when irradiated in parallel by UV irradiation. Using the immune fluorescent comet assay, IFCA, a variant of the comet assay, direct comparison of the effects of ionizing (137) Cs radiation with those of localized UV radiation is possible. When a laser microbeam is used to damage DNA in a cell nucleus with high temporal and spatial resolution, it can be observed directly how repair molecules accumulate (are recruited) at the site of damage. Comparison of the recruitment speed allows establishing an order of DNA repair events., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Photodegradation characteristics of pharmaceuticals and personal care products (PPCPs) and the effectiveness of H(2)O(2) addition for PPCPs photodegradation during UV treatment were examined in this study. Average k (1st order rate constant) value for all the PPCPs investigated increased by a factor of 1.3 by H(2)O(2) addition during UV treatment using biologically treated water (TW) spiked with the 30 PPCPs. Therefore, the effectiveness of H(2)O(2) addition for PPCPs removal during UV treatment in real wastewater treatment process was expected. It could be also known that H(2)O(2) addition would improve photodegradation rates of PPCPs highly resistant for UV treatment such as DEET, ethenzamide and theophylline. UV dose required for 90% degradation of each PPCP was calculated from k values obtained in UV and UV/H(2)O(2) treatment experiments using TW spiked with 30 PPCPs. For UV treatment, UV dose required for degrading each PPCP by 90% of initial concentration ranged from 38 mJ cm(-2) to 5644 mJ cm(-2), indicating that most of PPCPs will not be removed sufficiently in UV disinfection process in wastewater treatment plant. For UV/H(2)O(2) treatment, all the PPCPs except seven PPCPs including cyclophosphamide and 2-QCA were degraded by more than 90% by UV irradiation for 30 min (UV dose: 691 mJ cm(-2)), indicating that H(2)O(2) addition during UV treatment will be highly effective for improving the degradation of PPCPs by UV, even though much higher UV dose is still necessary comparing to for UV disinfection.

The application of sonolysis (US) for remediation of wastewater is an area of increasing interest. The aim of this study was to evaluate the ultrasonic (US) process on the degradation of pharmaceuticals (diclofenac (DCF), amoxicillin (AMX), carbamazepine (CBZ)) in single solutions and also in three mixtures spiked in urban wastewater effluent. Several operating conditions, such as power density (25-100 W L(-1)), initial substrate concentrations (2.5-10 mg L(-1)), initial solution pH (3-11), and air sparging were varied for the evaluation and understanding of the process. The degradation (as assessed by measuring UV absorbance), the generation of hydroxyl radicals (as assessed measuring H(2)O(2) concentration), the mineralization (in terms of TOC and COD removal), and the aerobic biodegradability (as assessed by the BOD(5)/COD ratio) were monitored during sonication. Ecotoxicity to Daphnia magna, Pseudokirchneriella subcapitata and Lepidium sativum before and after treatment was also evaluated. It was found that the pharmaceuticals conversion is enhanced at increased applied power densities, acidic conditions and in the presence of dissolved air. The reaction rate increases with increasing initial concentration of single pharmaceuticals but it remains constant in the mixtures, indicating different kinetic regimes (i.e. first and zero order respectively). Mineralization is a slow process as reaction by-products are more stable than pharmaceuticals to total oxidation; nonetheless, they are also more readily biodegradable. The toxicity of the wastewater samples before and after contamination with pharmaceuticals both in mixtures and in single substance-containing solutions was observed more severely on P. subcapitata; a fact that raises concerns in regards to the discharge of such effluents. D. magna displayed less sensitivity compared to P. subcapitata because it belongs in a lower taxonomic species than D. magna. The germination index of L. sativum in the presence of the drugs' mixture was stimulated instead of inducing any toxicity effect and this might be attributed to the fact the sample, laden with very low drug concentrations was able to act as a provider of additional nutrient elements.