Pharmaceuticals diclofenac

Deng, A., M. Himmelsbach, Q.Z. Zhu, et al. 2003. Residue analysis of the pharmaceutical diclofenac in different water types using ELISA and GC-MS. Environ. Sci. Technol. 37 3422-3429. 

Vogna et al. (2004) showed that UV/H2O2 (as well as molecular ozone) was effective at oxidizing transformation products of the pharmaceutical, diclofenac. Lau et al. (2007) studied the formation of a suite of ten transformation products of butylated hydroxyanisole by including 1,4-benzoquinone, f-butyl-l,4-benzoquinone, and hydroquinone. Some of the degradates were precipitated from solutions as an orange-colored solid that could be removed by filtration. The study showed that UV/ozone and ozonation were more effective than UV alone at removal of the parent and transformation products. 

Scheiwe, M.-W., D. Schilling, and P. Aebi, Near infrared spectroscopy analysis of intact pharmaceutical diclofenac coated tablets in transmission. Pharm. Ind., 61 179-183 (1999). 

Diclofenac is an exceedingly potent COX inhibitor slightly more efficacious against COX-2 than COX-1. Its absorption from the gastrointestinal tract varies according to the type of pharmaceutical formulation used. The oral bioavailability is only 30-80% due to a first-pass effect. Diclofenac is rapidly metabolised (hydroxylation and conjugation) and has a plasma half-life of 1.5 h. The metabolites are excreted renally and via the bile. 

Flaherty B, Paxeus N, Lo Giudice R, Pollio A, Garric J (2003) Ecotoxicological impact of pharmaceuticals found in treated wastewaters study of carbamazepine, clofibric acid, and diclofenac. Ecotoxicol Environ Saf 55 359-370... 

Among pharmacenticals, EE2 has been the snbject of particular recent attention becanse of its ability to canse endocrine disrnption in fish, as has been described in Chapter 15. Low levels of mixtnres of beta blockers, such as propranolol, metoprol, and nadolol have been detected in snrface waters, and there have been investigations of their possible effects on aqnatic invertebrates (Huggett et al. 2002). Veterinary medicines, too, have come nnder scrntiny for example, the dramatic effects of diclofenac on vnltnres, which will be discnssed shortly. Many questions remain to be answered abont the possible ecological effects of complex mixtures of pharmaceuticals and veterinary medicines. 

Buser H-R, T Poiger, MD Muller (1998) Occurrence and fate of the pharmaceutical drug diclofenac in surface waters rapid photodegradation in a lake. Environ Sci Technol 32 3449-3456. 

Stuer et al. [46] evaluated the presence of the 25 most used pharmaceuticals in the primary health sector in Denmark (e.g., paracetamol, acetyl salicylic acid, diazepam, and ibuprofen). They compared PECs with experimental determinations and they conclude that measured concentrations were in general within a factor of 2-5 of PECs. Carballa et al. [45] also determined PECs for pharmaceuticals (17), musk fragrances (2) and hormones (2) in sewage sludge matrix. For that purpose they used three different approaches (1) extrapolation of the per capita use in Europe to the number of Spanish inhabitants for musk fragrances (2) annual prescription items multiplied by the average daily dose for pharmaceuticals and (3) excretion rates of different groups of population for hormones. They indicated that these PECs fitted with the measured values for half of them (carbamazepine, diazepam, ibuprofen, naproxen, diclofenac, sulfamethoxazole, roxithromycin, erythromycin, and 17a-ethiny I e strad iol). 

In order to determine more precisely the fate of pharmaceuticals during sludge treatment, different experiments have been conducted in controlled conditions. In continuous anaerobic reactors treating sludge spiked with pharmaceuticals, Carballa et al. [114] observed removals higher than 80% for naproxen, sulfamethoxazole, and roxithromycin, while 40% and 23% of ibuprofen and iopromide, respectively, were eliminated at both mesophilic (37°C) and thermophilic (55°C) temperatures. For diclofenac and diazepam, elimination of about 60% was observed in mesophilic conditions while in thermophilic conditions, 38% and 73% of these two compounds, respectively, were eliminated. In these experiments, the sludge retention time (15 or 30 days) did not seem to influence pharmaceutical removal... 

Conventional WWTPs are, therefore, unable to remove wide ranges of pharmaceuticals and other compounds. For pharmaceuticals, although acute toxicity of aquatic organisms or chronic effects are unlikely with the present concentrations due to dilution effects, a wide range of pharmaceuticals are detected in the Ebro, and the overall toxicity of mixed pharmaceuticals may be high. Further studies are therefore required to assess the interactions of different compounds and the consequential health effects. In a similar manner to other pollutants, pharmaceuticals have a clear sensitivity to climate change through dilution effects, and the projected future decrease in annual precipitation could cause certain compound concentrations (e.g. anti-inflammatory diclofenac and p-blocker pranolol) to reach levels which may cause chronic effects [76]. 

It is a well-known fact that a pharmaceutical substance can be prepared by adopting different routes of synthesis based upon the dynamic ongoing research in the field of organic-reaction-mechanisms. Relentless efforts are exerted vigorously by reputed research laboratories across the world to look for shorter routes of synthesis bearing in mind the cost-effectiveness of the final product. For instance diclofenac sodium (an NSAID) can be manufactured by two methods, one using a bromo compound as a starting material while the other is based on a non-bromo compound. Nevertheless, the latter product is more in demand because it is completely devoid of bromine residues in the final product. 

Vogna D, Marotta R, Napolitano A, Andreozzi R, d Ischia M (2004) Advanced oxidation of the pharmaceutical drug diclofenac with UV/H2O2 and ozone. Water Res 38 414-422... 

Bioactive compounds from Blumea gariepina salicin, salicylic acid, tenoxicam, ketorolac, piroxicam, tolmetin, naproxen, flurbiprofin, diclofenac, and ibuprofen in pharmaceutical formulations and biological samples ... 

Diclofenac has been identified as one of the major pharmaceuticals in the waters in Berlin (Germany) at median concentrations of 0.47 pgL (Ternes et al., 2002 Ferrari et al., 2003). Other analgesics such as naproxen, phenazone, codeine, indome-tacin, fenoprofen, ketoprofen, phenylbutazone, and propyphenazone have also been detected in sewage and surface water (Heberer and Adam, 2005 Boyd et al., 2005), although data about their occurrence in the environment are not extensive. The data presented in Figure 2.5 are not exhaustive but are rather intended to show the great diversity in concentrations of some of the key PPCPs in wastewater. 

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