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The oral route is the most preferred route of drug administration. Tablets are the most prominent oral dosage form as they can provide greater dose precision, higher stability, simplicity and lower cost of manufacturing and suitability for large-scale production. Compressed tablets, which are the most widely used tablets, consist of a blend of one or more active pharmaceutical ingredients (APIs) with suitable excipients. The excipients in tablets, in particular dissolution enhancing excipients, play a vital role in ensuring an efficient oral drug delivery (i.e., high oral bioavailability). These excipients are usually utilized as a part of a solubilization strategy to enhance the drug solubility, and thus its oral bioavailability. However, various excipients in tablets are associated with instability issues, hence, a comprehensive, costly, and time-consuming investigation of excipients is essential to develop stable and efficient tablets. SmartFilms technology is an innovative strategy which enhances the drug aqueous solubility via embedding the drug within a matrix of cellulose-based paper in an amorphous state. Despite its proven effectiveness, smartFilms technology remains unrecognized by the pharmaceutical industry due to the difficulty of large-scale production of paper tablets from paper cut outs with limited flowability. The inadequate flowability might obstruct the compression process due to the adherence of the paper to the tablet press, which might result in dose variation of the tablets. In addition, the influence of the smartFilm tablets on the bioactivity of the loaded drug is still ambiguous. In this thesis, smartFilm tablets were investigated as a potential, industrially feasible approach for an improved solubility and bioactivity of poorly water-soluble APIs. The first part of the thesis investigated the possibility of transforming unloaded smartFilms (i.e., paper) into a flowable physical form and the influence of sucrose as a binder (i.e., amounts and forms) on the behavior of the material under compression as well as the properties of the obtained tablets. Cellulose-based paper utilized in this work was successfully transformed into granules via a wet granulation process. The obtained unloaded paper granules exhibited a slightly elongated shape, demonstrated good flowability and allowed the production of tablets in a continuous mode. The results also showed that using sucrose as a dry powder during the granulation process was the most suitable for obtaining paper granules that can be compressed in large scale into tablets with good pharmaceutical properties (i.e., in accordance with the European Pharmacopoeia). Investigating the mechanical behavior of paper granules under compression indicated that the compaction behavior of these granules was comparable to the behavior of classical binders and compression enhancers. These findings indicate that the obtained paper granules have good flowability, a suitable compression behavior and propose paper granules as suitable intermediate products for the production of tablets made from paper on a large, industrial scale. The second and the third part of the thesis studied the impact of smartFilm tablets on the oral delivery and bioactivity of two poorly water-soluble APIs (i.e., curcumin and norfloxacin) using an ex vivo porcine intestinal model. Curcumin-loaded smartFilms and norfloxacin-loaded smartFilms were successfully transferred into smartFilm granules and smartFilm tablets, respectively. Results also showed that the curcumin-loaded smartFilm granules and smartFilm tablets preserved the amorphous state of the incorporated drug. The obtained tablets also fulfilled the criteria according to the European Pharmacopoeia regarding hardness, friability, content uniformity, mass uniformity, and disintegration time. The incorporation of curcumin or norfloxacin into smartFilm tablets resulted in increasing the dissolution rate (approx. two-fold) especially at the beginning of the release. The ex vivo intestinal permeability of curcumin from the smartFilm tablets was also studied and compared to a physical mixture of curcumin and paper and to a classical and an innovative commercial product, respectively. The innovative product contains curcumin in a micellar form and has previously demonstrated an exceptional oral bioavailability. The findings showed an enhanced intestinal permeability of curcumin from the smartFilm tablets, as compared to the physical mixture tablet and the classical marketed product that contains curcumin as a raw powder (approx. two-fold increase). No difference in the total amount of permeated curcumin was found between the smartFilm tablets and the innovative commercial product (i.e., micellar curcumin). Nevertheless, a trend towards a deeper intestinal permeation of the curcumin from the smartFilm tablets was observed. These outcomes indicate that smartFilm tablets can be equally efficient as innovative and classical curcumin formulation approaches in improving the oral bioavailability of curcumin. The ex vivo bioactivity of norfloxacin from the smartFilm tablets was also investigated and showed a similar trend (i.e., a two-fold higher antibacterial activity of norfloxacin from the smartFilm tablets when compared to the physical mixture tablet). The findings of this thesis provide evidence that smartFilm tablets are a cost-effective, universal, industrially feasible formulation approach for improved solubility and enhanced bioactivity of poorly water-soluble APIs, i.e., BCS class II and IV drugs.

Murray-Darling Freshwater Research CentreMDFRC item.Filter-papers impregnated with iron oxides (“iron-strips”) are increasingly being used to estimate “bioavailable” phosphorus. This study shows that these strips, in addition to being able to adsorb phosphate ions, can also mediate the hydrolysis of a model organic phosphorus compound. It is proposed that the high correlation between bioavailable phosphorus and iron-strip available phosphorus is due in part to the strips' hydrolytic capability.

Contamination and associated risks posed by cadmium (Cd) and chromium (Cr) were characterized in the soils being continuously exposed by paper mill waste discharge in Assam, India. Soil samples from 20 (S-1 to S-20) sites surrounding a paper mill were analyzed by sequential extraction technique for Cd and Cr to assess the potential mobility and bioavailability of these heavy metals in the soils. Cadmium was mostly found in its carbonate fraction (37.14%) whereas; Cr was mostly available in Fe-Mn oxide bound fraction (34.72%). Relatively low amounts of Cd and Cr were associated with the water soluble fractions. The pollution load index (P i) values of Cd exceeded the maximum permissible limit i.e. 1 in all the sites but, for Cr it exceeded in all sites but S-7, S-13 and S-16. The mobility factor values ranged from 47.4% to 87.1% for Cd and 12.8–67.2% for Cr. High mobility factor values represent relatively higher biological availability in the soil samples and thus could pose environmental threats in the area surrounding the paper mill. The high values of other contamination factors, viz. individual and global contamination factors, potential ecological risk factor, ecological risk index and geo-accumulation index indicated that the studied area was widely polluted by Cd and Cr as a result of the effluents discharged from the paper mill.

Heavy metal content has become a serious issue with increase in compost application in agricultural land. The bioavailable fraction (water soluble and diethylene triamine pentaacetic acid (DTPA) extractable) is the major concern comparing to the total concentration as it can be taken up by plants which in turn affects the human health. Thus, this study was carried out to determine the variation in bioavailable and leachable fraction of heavy metals (Cd, Cu, Fe, Ni, Pb, Cr, Zn, Hg and Mn) and to assess the influence of temperature, pH, organic matter degradation and humification during rotary drum composting of paper mill sludge (PMS) for 20 days. A total concentration of all the metals as well as nutrients increased during composting. The Hg was not detected in water soluble and DTPA extractable fraction, whereas Pb and Cr were also not detected in water soluble fraction in all the trials. A decreasing trend was observed in leachable quantity for all the metals during composting. Water extractable quantity increased for Fe and Cu during composting. Organic matter degradation and humification during composting influences the variation in bioavailability and leachability of heavy metals, which can be optimized by applying appropriate proportion of cow dung during rotary drum composting of PMS.

Speciation of heavy metals (Cu, Cr, Pb, Ni, Cd and Zn) during anaerobic co-disposal of two distinct paper mill sludges viz. effluent treatment plant sludge and de-inking plant sludge with municipal solid waste in anaerobic landfill bioreactor was investigated. Effects of moisture content, volatile solids and pH on fractionation of heavy metals over the course of landfilling were also analyzed. Study revealed enhancement in bioavailability of Cu, Cr, Ni and Cd on sole disposal municipal solid waste in bioreactor landfill over 300 days. However, co-disposal of effluent treatment plant sludge with municipal solid waste showed reduction in bioavailability of every analyzed heavy metals with maximum increment in stable residual forms of Cu, Cr, Pb, Ni and Zn by 3.70 %, 0.73 %, 3.08 %, 1.17 % and 3.45 % (dry weight), respectively. De-inking sludge co-disposal was also found effective for reducing bioavailability of Cu, Cd and Zn while bioavailability of Cr, Ni and Pb was unaltered. Strong correlations between increase in residual forms of heavy metals and volatile solid reduction obtained for both co-disposed bioreactors.

An increasing proportion of recycled fibers are used in paper industries due to their important environmental and economic benefits. However, removing the ink, clay, coatings and contaminants from paper waste in order to produce recycled fibers creates large amounts of de-inking paper sludge. For this reason, the preparation of biochar from pyrolysis process of this kind of waste rich in cellulose fibers, carbonates and clays, and their use in soil remediation contaminated by heavy metals can be perceived as an interesting valorization alternative. The aim of the present work is to study the influence of biochar from de-inking paper sludge (HP) pyrolysis in a Ni2+ polluted soil. Selected soil (S) was artificially contaminated with Ni2+ at 1000 mg Ni kg(-1) (S1000) and then amended at a rate of 5 wt% using HP and two biochars prepared from pyrolysis of HP at 300 degrees C (HP300) and 500 degrees C (HP500). Non-contaminated soil (S) was used as control and amended with the same rate of HP, HP300 and HP500. An incubation experiment was designed and soil CO2 emissions were measured in the different treatments during 77 days. The results have shown that CO2 emissions followed the order S = S + HP = S + HP300 > S + HP500 for the non-polluted soil and the patternS1000 + HP300 > S1000 approximate to S1000 + HP > S1000 + HP500 for the soil spiked with Ni. Finally, it was observed that HP500 addition to the polluted soil reduced the quantity of mobile, leached and bioavailable Ni.

Objective: The objective of this study was to formulate orodispersible tablets containing empagliflozin by direct compression method with sufficient hardness and rapid disintegration time and to study the effect of functionality differences of super-disintegrants on the tablet properties. Methods: A two factor three level factorial design (32) was used for the formulation optimization of orodispersible tablets of Empagliflozin and experimental trials were performed on all possible formulations, in which the amount of β-cyclodextrin, crospovidone and croscarmellose sodium were selected as independent variables (factor) varied at three different levels: low (-1), medium (0), and high (+1) levels. The drug release and disintegration time were used as dependent variables (response). All formulations were characterized for parameters such as diameter, hardness, weight, thickness, friability, disintegration time, drug release. Results: Formulation FD6 having 30 sec disintegration time, 98.84% drug release after 30 min, 2.8 kg/cm2 hardness and 0.292% friability was found best among all formulations and selected as an optimized formulation with rapid onset of action and enhanced bioavailability (more than 98% drug release within 30 min.) as compared to the oral empagliflozin tablet. Conclusion: Empagliflozin orodispersible tablets with different superdisintegrants were successfully prepared and formulation containing highest percentage of crospovidone was found best among all other formulations in terms of bioavailability and rapid onset of action.

This study investigated the morphology and potentially toxic metal concentrations of paper waste-based biochar (PB) and kitchen waste-based biochar (KB) obtained at 500 and 700 °C. The morphology and potentially toxic metals (Cr, Mn, Cu, Cd, Pb, Zn, Ag, and Ba) concentrations in the biochars were determined by SEM and FT-IR analysis. The Cr, Mn, Cu, and Cd concentrations in PB were low, while the Ba content was relatively high at 0.1 mg∙kg−1. An increase in the terminal temperature led to an increase in the concentrations of Fe/Mn oxide-bound potentially toxic metals of PB, and a decrease in the concentrations of organic matter-bound potentially toxic metals. The Fe/Mn oxide-bound Cr, Mn, Cu, Pb, and Zn concentrations of KB decreased with an increase in the terminal temperature. Therefore, increasing the terminal temperature could reduce the bioavailability of potentially toxic metals in PB and KB. The environmental risk of the different biochars when used for soil remediation was assessed by the potential ecological risk index (RI), and a case study of a Tibetan soil was also conducted. The potentially toxic metal concentrations leached from both PB and KB were lower than the relevant standards. The findings showed that both PB and KB can be safely used for soil remediation.

Introduction Studies have suggested that free radicals-induced neurodegeneration is one of the many studies of Parkinson Disease (PD). Quercetin as a natural polyphenol has been regarded as a significant player in altering the progression of neurodegenerative diseases by protecting from damages caused by free radicals. Owing to its poor water solubility, preparation of its oral formulation is urgently needed. Recently, nanocrystal technique as an effective way has been introduced for oral administration of drugs. Methods This study investigated the neuroprotective effects of quercetin nanocrystals on 6-hydroxydopamine (6-OHDA)-induced Parkinson-like model in male rats. Quercetin nanocrystals were prepared by the Evaporative Precipitation of Nanosuspension (EPN) method. Results Administration of quercetin and its nanocrystals (10 and 25 mg/kg) prevented disruption of memory, increased antioxidant enzyme activities (superoxide dismutase and catalase) and total glutathione and reduced Malondialdehyde (MDA) level in the hippocampal area. Conclusion The present study results demonstrated that quercetin nanocrystals with greater bioavailability is effective than quercetin alone in treatment of Parkinson-like model in rat.

We determined the potentially algal-available P (P(aa)) in pulp and paper mill effluents by two bioassay techniques (a dual-culture assay and a batch approach) and compared it with chemically analysed P (total P, total dissolved P, reactive P, dissolved reactive P and dissolved hydrolysable P). The mean P(aa) given by the dual-culture assay was within a 40% range of that given by the batch approach. The P(aa) obtained by both bioassays differed from total P. Dissolved reactive P appeared to be the most readily available chemical P fraction, but other P fractions also contributed to P(aa). The analysis of reactive P, which involves direct staining of an unfiltered sample, best approximated the P(aa) given by the dual-culture assay (relative error 9%). The results suggest that assessment of eutrophying effluent P can be improved by analysing simple chemical P fractions in wastewater. The fractions to be analysed, however, may be site specific.

International audience; Bisphenol A (BPA) is an endocrine disrupting environmental contaminant used in a wide variety of products, and BPA metabolites are found in almost everyone's urine, suggesting widespread exposure from multiple sources. Regulatory agencies estimate that virtually all BPA exposure is from food and beverage packaging. However, free BPA is applied to the outer layer of thermal receipt paper present in very high (∼20 mg BPA/g paper) quantities as a print developer. Not taken into account when considering thermal paper as a source of BPA exposure is that some commonly used hand sanitizers, as well as other skin care products, contain mixtures of dermal penetration enhancing chemicals that can increase by up to 100 fold the dermal absorption of lipophilic compounds such as BPA. We found that when men and women held thermal receipt paper immediately after using a hand sanitizer with penetration enhancing chemicals, significant free BPA was transferred to their hands and then to French fries that were eaten, and the combination of dermal and oral BPA absorption led to a rapid and dramatic average maximum increase (Cmax) in unconjugated (bioactive) BPA of ∼7 ng/mL in serum and ∼20 µg total BPA/g creatinine in urine within 90 min. The default method used by regulatory agencies to test for hazards posed by chemicals is intra-gastric gavage. For BPA this approach results in less than 1% of the administered dose being bioavailable in blood. It also ignores dermal absorption as well as sublingual absorption in the mouth that both bypass first-pass liver metabolism. The elevated levels of BPA that we observed due to holding thermal paper after using a product containing dermal penetration enhancing chemicals have been related to an increased risk for a wide range of developmental abnormalities as well as diseases in adults.

The risk analysis was performed to study the bioavailability and eco-toxicity of heavy metals in biochar obtained from pyrolysis of sludge of pulp and paper mill effluent treatment plant. The sludge was pyrolyzed at different temperatures (200-700°C) and the resultant biochar were analyzed for fractionation of heavy metals by sequential extraction procedure. It was observed that all the heavy metals get enriched in biochar matrix after pyrolysis, but the bioavailability and eco-toxicity of the heavy metals in biochar were significantly reduced as the mobile and bioavailable heavy metal fractions were transformed into the relatively stable fractions. Moreover, it was observed that the leaching potential of heavy metals decreased after pyrolysis and the best results were obtained for biochar pyrolyzed at 700°C.

Heavy metal contamination of soil poses risks and hazards to environment and human being. Many amendments were used to remediate the contaminated soil. In this report, paper sludge was used to reduce the bioavailability of Pb in soil, and the remediation mechanism was studied by investigating the redistribution of Pb speciation after paper sludge addition. In pot experiments, significantly increased weights of shoots (from 1.6 to 3.3 mg per plant) and roots (from 0.7 to 0.8 mg per plant), as well as significantly decreased Pb content in shoots (from 153.8 to 24.4 mg kg−1) and roots (from 467.1 to 38.0 mg kg−1) of rape were observed after paper sludge was added. The addition of paper sludge resulted in redistribution of Pb from the liable fractions (carbonate-bound Pb from 58.3 to 3.7%) to the Fe–Mn oxide-bound fraction (from 29.2 to 74.9%). Paper sludge addition increased the content of organic matters and pH of soil, and induced Pb redistribution, which ultimately inhibited Pb uptake and improved...

This study examined the physical, chemical and biological characteristics of the phosphorus (P) in the effluents from a paper processing facility before and after an alum based P removal process. The alum based treatment process reduced effluent total P concentrations from an average of 230 ± 103 (±1 SD) μg L−1 to an average of 36 ± 10 μg L−1. Ultra-filtration showed the treatment process shifted the P in these effluents from being 75 ± 9% particulate pre-removal to being 52 ± 0% dissolved and 27 ± 1% colloidal after the Trident P removal process. The alum removal process also reduced the fraction of reactive P in the dissolved and colloidal pools from 55% to 14%, respectively. Algal phosphorus bioavailability (BAP) bioassays showed the BAP of these effluents averaged 12 ± 9% of total P. Algal dissolved P uptake experiments indicated ≈ 30% of the dissolved P was converted to particulate P (which usually indicates algal uptake) during 21-day bioassays. However, treatments without algae indicated >80% of the apparent algal uptake may have been due to colloidal P forming flocs via physical-chemical processes. These analyses indicate the phosphorus contained in this paper processing facility's effluents had much lower bioavailability than the P in typical municipal wastewater treatment plant effluents.

At present, pharmaceutical researchers are focusing on instantaneous intraoral dispersible technologies as novel drug delivery systems because; they have outstanding advantages over the traditional oral and parenteral routes of drug administration. Some essential natural drugs have low oral bioavailability due to extensive first pass metabolism and pre systemic degradation in the gastrointestinal tract. Now, a cheap rice paper Intraoral Dispersible Film (IDF) has been developed. In this study, formulation was optimized using the experimental factorial design. The IDFs were loaded with model, natural, anti-cancer drugs, Resveratrol and Curcumin with low oral bioavailability. They were evaluated for thickness, folding endurance, swelling behaviour, among others. These related to their drug release properties. Permeation was evaluated using the pig mucosal membrane mounted on a Franz diffusion cell. Taste testing was done to determine acceptability using a taste panel. Sixteen formulations showed variations in their profiles. Formulation 16 proved optimal. The dissolution rate at steady state concentrations of Resveratrol was 29 mg per second and the Permeability coefficient was 389 mg/sec.cm2. Curcumin dissolution rate at steady state concentrations was 0.25 mg per second and the Permeability coefficient was 42.71 mg/sec.cm2. Resveratrol permeability rate was 0.42 mg/sec. And that of Curcumin was 0.14 mg/sec. Resveratrol Flux was 0.21 mg/sec./cm2. Curcumin Flux was 0.14 mg/sec. / cm2. Drug entrapment was 80% for both molecules. The 20 mg of Resveratrol and Curcumin dissolved in 47.6 sec. and 71.4 sec. respectively. In this study, after permeation, a concentration of 6.73 mg/ml of Resveratrol and 0.061 mg/ml of Curcumin were detected after 2 hours of the experiment on administering only 20 mg of each of the drugs suggesting that Curcumin is 100 times less permeable than Resveratrol. The release profile was a burst release. On contrast, Curcumin oral dose of 2 g/kg to rats yielded 1.35 ± 0.23 μg/ml in 0.83 hours and in humans, given the same dose yielded either undetectable or extremely low (0.006 ± 0.005 μg/ml after 1 hour in blood. Two separate monoglucuronide metabolites yielded a Cmax of ~7.5 μm following a single 5.0 g oral dosage of Resveratrol. The key finding was, ex vivo release profiles of the optimized formulation revealed first order release and later zero order. Therefore, it is evident that rice paper IDF could efficiently deliver natural drugs into the systemic circulation intraorally. However, further studies using human subjects need to be performed to prove increased bioavailability in human subjects (Graphical Abstract).

The aim of this study was to examine the stability and bioavailability of different phosphorus fractions of pulp and paper mill effluents in order to assess the environmental benefits of reducing their phosphorus discharges. Two types of effluent were studied: activated sludge treated bleached kraft mill effluent and activated sludge treated paper mill effluent. Phosphorus was characterized on the basis of its solubility and chemical reactivity. The stability of particulate phosphorus was studied in long-term (6-8 weeks) degradation tests. The bioavailability of different phosphorus fractions was measured by algal growth potential tests. In bleached kraft mill effluent (BKME) the proportion of dissolved phosphorus in relation to the total phosphorus was on an average 80%, and of this, approximately 80-90% was reactive phosphorus. During a 6-8 week incubation period some 60-70% of the particulate phosphorus in BKME was dissolved as soluble phosphorus, and most of it was of the reactive type. Approximately 90% of the dissolved phosphorus and 45% of the particulate phosphorus in BKME was biologically available phosphorus (BAP). Altogether some 80% of the total phosphorus in activated sludge treated BKME was available for algae either immediately or after inherent degradation. The percentages of dissolved and particulate phosphorus of paper mill effluent (PME) total phosphorus were of the same order of magnitude as those of BKME, but less than 20% of the dissolved phosphorus was of the reactive type. Approximately 50-60% of the particulate phosphorus in PME was dissolved in degradation tests, and 90% of it was biologically available.

This is an open access article under the terms of the Creative Commons Attribution-Non-Commercial-NoDerivs Licence.-- et al., Various secondary plant metabolites or phytochemicals, including polyphenols and carotenoids, have been associated with a variety of health benefits, such as reduced incidence of type 2 diabetes, cardiovascular diseases, and several types of cancer, most likely due to their involvement in ameliorating inflammation and oxidative stress. However, discrepancies exist between their putative effects when comparing observational and intervention studies, especially when using pure compounds. These discrepancies may in part be explained by differences in intake levels and their bioavailability. Prior to exerting their bioactivity, these compounds must be made bioavailable, and considerable differences may arise due to their matrix release, changes during digestion, uptake, metabolism, and biodistribution, even before considering dose- and host-related factors. Though many insights have been gained on factors affecting secondary plant metabolite bioavailability, many gaps still exist in our knowledge. In this position paper, we highlight several major gaps in our understanding of phytochemical bioavailability, including effects of food processing, changes during digestion, involvement of cellular transporters in influx/efflux through the gastrointestinal epithelium, changes during colonic fermentation, and their phase I and phase II metabolism following absorption., The EU-COST FA 1005 Infogest action is greatly acknowledged for providing funding for travel and meetings and allowing for open access.

Lab-scale tests have been conducted on the reduction of residual COD in biologically purified effluents from mills with integrated waste paper treatment plants and/or TMP lines. For this purpose, waste water samples were subjected to ozonization or a combined ozone/UV treatment at varied temperatures and pHs. The influence of ozone on the biodegradability of biologically part-treated effluents was studied by means of the Zahn-Wellens test. For specific ozone consumption rates < 2.5 g O3/g eliminated COD, COD elimination rates of up to 82% and DOC elimination rates of up to 64% were obtained. Ozone consumption was considerably higher for a combined ozone/UV treatment or treatment at pH > 9 or at elevated temperatures (40°C). For colour stripping of the waste waters and for destroying the surfactants contained in them, ozone additions of up to 80 mg O3/l waste water were required. The bioavailability of effluents that have been part-treated biologically in trickling filters or anaerobic stages to COD > 500 mg/l and BOD5/COD > 0.2 cannot be positively influenced by ozonization with up to 1.8 g O3/l waste water. On the other hand, in fully biologically treated effluents (COD < 500 mg/l), ozonization brought about a rise in the BOD5/COD ratio from an initial < 0.05 to a maximum of 0.37 - an observation which clearly demonstrates an increase in bio-degradability.

Industrial residue application to soil was investigated by integrating granulated blast furnace or converter steel slag with residues from the pulp and paper industry in various formulations. Specimen analysis included relevant physicochemical properties, total element concentrations (HCl+HNO3 digestion, USEPA 3051) and chemical speciation of chosen heavy metals (CH3COOH, NH2OH·HCl and H2O2+H2O2+CH3COONH4, the BCR method). Produced matrices showed liming effects comparable to commercial ground limestone and included significant quantities of soluble vital nutrients. The use of converter steel slag, however, led to significant increases in the total concentrations of Cr and V. Subsequently, total Cr was attested to occur as Cr(III) by Na2CO3+NaOH digestion followed by IC UV/VIS-PCR (USEPA 3060A). Additionally, 80.6% of the total concentration of Cr (370 mg kg(-1), d.w.) occurred in the residual fraction. However, 46.0% of the total concentration of V (2470 mg kg(-1), d.w.) occurred in the easily reduced fraction indicating potential bioavailability.

Sources of human exposure to perfluorinated carboxylic acids (PFCAs) are not well-characterized. Polyfluoroalkyl phosphoric acids (PAPs) are fluorinated surfactants used in human food contact paper products. PAPs can migrate into food and food simulants, and their bioavailability and biotransformation into PFCAs has been demonstrated using a rat model. To characterize human exposure to PAP materials, we analyzed pooled human sera samples collected in 2004 and 2005 (n = 10) and 2008 (n = 10) from the midwestern United States for the 4:2 through 10:2 PAP diesters (diPAPs). The 2004 and 2005 sera samples contained 4.5 microg/L total diPAPs, with the 6:2 diPAP dominating the congener profile at 1.9 +/- 0.4 microg/L DiPAP concentrations observed in the 2004 and 2005 human sera samples were similar to those of the C8 to C11 PFCAs (0.13 +/- 0.01 to 4.2 +/- 0.3 microg/L) monitored in the same samples. 6:2 diPAP was also consistently observed in the 2008 human sera samples at a mean concentration of 0.63 +/- 0.13 microg/L As diPAPs have been shown to degrade to PFCAs in vivo, our observation of diPAPs in human sera may be a direct connection between the legacy of human PFCA contamination and PAPs commercial applications. Wastewater treatment plant (WWTP) sludge and paper fibers were analyzed for diPAPs as a proxy for human use and potential exposure to diPAPs. DiPAPs were observed in WWTP sludge at concentrations ranging from 47 +/- 22 to 200 +/- 130 ng/g, a range similar to perfluorooctane sulfonic acid (PFOS) (100 +/- 70 ng/g) and greater than the C8 to C11 PFCAs (1.6 +/- 0.6 to 0.17 +/- 0.10 ng/g) observed in the same samples. DiPAPs were observed in paper fiber extracts at concentrations ranging from 34 +/- 30 to 2200 +/- 400 ng/g. The high diPAP concentrations in WWTP sludge suggest PAP materials may be prevalent in our daily lives.

Statins (HMG-CoA reductase inhibitors) are a group of highly efficient pharmacological agents used for reducing blood cholesterol level and prevention/treatment of cardiovascular disease. Adverse reactions during statin treatment affect quite significant numbers of patients (reportedly from 5% to 20%), with more side effects occurring at higher doses. Reduced statin dosing can be achieved by improved bioavailability of statins, which is fairly low due to poor aqueous solubility, low permeability and high molecular weight of some members of the statin family. Moreover, since hepatic cholesterologenesis is a main target of statin action and extrahepatic inhibition of HMG-CoA reductase has no effect on plasma lipids, hepatic bioavailability, in our opinion, becomes a new important modality of statins maximizing their potential effect on the plasma lipid profile and diminishing their extrahepatic toxicity. Therefore efficient delivery systems of statins into hepatocytes need to be developed and introduced. Uses of nano-emulsifying statin delivery systems which may include vectors of intrahepatic transport, in particular lycopene, are discussed. As a proof of concept, some preliminary results revealing the effect of a lycopene-containing nanoformulation of simvastatin (designated as Lyco-Simvastatin) on LDL in mildly hypercholesterolemic patients are shown.

Paper constitutes about 38% of municipal solid waste, much of which is disposed of in landfills. Sorption to such lignocellulosic materials may limit the bioavailability of organic contaminants in landfills. The objective of this study was to identify the effect of individual biopolymers in paper on toluene sorption and bioavailability by subjecting fresh and anaerobically degraded office paper and newsprint to enzymatic hydrolysis and acid hydrolysis. Enzymatic degradation of cellulose and hemicellulose had no effect on toluene bioavailability. In contrast, acid-insoluble lignin controlled toluene sorption and bioavailability for both fresh and degraded newsprint. Acid-insoluble lignin could explain only 54% of the toluene sorption capacity of degraded office paper however, suggesting that crude protein and/or lipophilic organic matter were also important sorbent phases. Toluene sorbed to degraded office paper was also less bioavailable than toluene sorbed to an equivalent mass of lignin extracted from this sorbent. The latter result suggests that a fraction of toluene sorbed to degraded office paper may have been sequestered by lipophilic organic matter. The sorption and bioavailability data indicate that the preferential decomposition of cellulose and hemicellulose relative to lignin in landfills should not decrease the overall toluene sorption capacity of paperwaste or increase the bioavailability of sorbed toluene.

Phytochemicals have gained significant recognition for their potential therapeutic uses against a variety of human diseases. However, the poor water solubility, limited intestinal absorption and low water stability of phytochemicals generally prevent from achieving a high oral bioavailability and even detectable plasma levels of the parent compound. Dose escalation is not always a solution to address limited oral bioavailability, and may increase the risk of adverse events, most frequently in the gastrointestinal system [1]. Low water solubility is a common reason for the limited bioavailability of drug candidates because passing through the unstirred aqueous layer on the surface of the intestinal epithelium is a pre-requisite for the intestinal absorption of compounds. It has been estimated that over 40 % of the drugs being identified through combinatorial screening programs are poorly soluble in water [2]. Therefore, formulation improvement into highly stable, water-soluble and orally bioavailable forms is regarded as a prerequisite for the clinical application of phytochemicals. Nanotechnology has emerged as an efficient tool to address the problems regarding solubility, stability and oral bioavailability of phytochemicals [3]. Several nano-sized delivery systems have been utilized to enhance the physicochemical properties of phytochemicals. Characteristics of the most common biocompatible and biodegradable nanoparticulate systems used for the delivery of natural products are summarized in Table 1. Nanoparticulate delivery systems confer a number of advantages, including facilitated transport of incorporated phytochemicals across the biological barriers, enhanced bioavailability of poorly water-soluble phytochemicals, targeted delivery of phytochemicals, protection of sensitive compounds from biological and environmental degradation, and controlled release [4]. Some famous examples of nanoformulated phytochemicals are shown in Table 2 [5-7]. Furthermore, many nanomaterials are being studied in clinical trials or have been approved by the Food and Drug Administration to be used in humans. Liposomal daunorubicin (Daunoxome®; described in patents EP0004467 and US20070286897) and albumin-bound paclitaxel (Abraxane®, described in patents WO2014105644 and WO2008057562) are two breakthrough examples of successful formulation of natural products using nanotechnology-based approaches. Table 2 summarizes some pharmacologically important phytochemicals with optimized nanoformulations [8, 9]. Curcumin is another important anti-cancer and cardioprotective phytopharmaceutical [10-12] for which various nanoformulations have been developed [12], as described in patents WO2013108270 and EP2349237. While nanotechnology offers promising solutions for the formulation of phytochemicals, some challenges still remain to be overcome before developing any nanoparticulate system to be used in clinical practice. These considerations include potential long-term toxicity of nanoparticles, non-specific uptake into cells, off-target biodistribution and tissue accumulation, and costly and complicated manufacturing process of some nanocomposites particularly in the targeted forms [8]. In spite of these challenges, biocompatible and biodegradable nanocarriers are increasingly finding applications in pharmaceutical and nutraceutical industries. Future investigations should address long-term safety issues of nanomaterials particularly when used repeatedly for chronic diseases.

Edible nanoencapsulation vehicles (ENVs) designed for the delivery of phytochemicals have gained increasing research interest. The major driving force for this trend is the potential bioavailability enhancement effect for phytochemicals when delivered via ENVs. ENVs affect the bioefficacy of phytochemicals by influencing their dispersion and gastrointestinal stability, rate and site of release, transportation efficiency across the endothelial layer, systemic circulation and biodistribution, and regulation of gut microflora. Enhanced bioefficacy can be achieved by rational design of the size, surface property, matrix materials, and compartment structure of ENVs according to properties of phytochemicals. Future investigations may lay particular emphasis on examining the relevance between results gained by in vitro digestion simulations and those obtained via in vivo digestion simulations, structural evolutions of ENVs during digestion and absorption, impacts of ENVs on the metabolism of phytochemicals, and using ENVs for deciphering the reciprocal interactions between phytochemicals and gut microbiota.

Background Interest in vegetarian diets is growing in Italy and elsewhere, as government agencies and health/nutrition organizations are emphasizing that regular consumption of plant foods may provide health benefits and help prevent certain diseases. Methods and results We conducted a Pubmed search, up to September, 2015, for studies on key nutrients (proteins, vitamin B12, iron, zinc, calcium, vitamin D, and n-3 fatty acids) in vegetarian diets. From 295 eligible publications the following emerged: Vegetarians should be encouraged to supplement their diets with a reliable source of vitamin B12 (vitamin-fortified foods or supplements). Since the plant protein digestibility is lower than that of animal proteins it may be appropriate for vegetarians to consume more proteins than recommended for the general population. Vegetarians should also be encouraged to habitually consume good sources of calcium, iron and zinc – particularly vegetables that are low in oxalate and phytate (e.g. Brassicaceae), nuts and seeds, and calcium-rich mineral water. Calcium, iron, and zinc bioavailability can be improved by soaking, germination, and sour-dough leavening that lower the phytate content of pulses and cereals. Vegetarians can ensure good n-3 fatty acid status by habitually consuming good sources of a-linolenic acid (walnuts, flaxseeds, chia seeds, and their oils) and limiting linoleic acid intake (corn and sunflower oils). Conclusions Well-planned vegetarian diets that include a wide variety of plant foods, and a reliable source of vitamin B12, provide adequate nutrient intake. Government agencies and health/nutrition organizations should provide more educational resources to help Italians consume nutritionally adequate vegetarian diets.

In organic soil fertility management, rock phosphate (RP) is gaining momentum as an acceptable phosphorus source, though much of this P is not bioavailable for plant uptake, particularly in igneous RP. This study evaluated the nutrient solubilization, biodegradation and heavy metal concentration when cow dung – waste paper mixture amended with increasing rates of igneous RP was vermicomposted with E. fetida. The cow dung was optimized to a C/N ratio of 30 using waste paper and amended with RP to provide 0%; 2%; 4% and 8% of elemental phosphorus on a dry w/w basis. Incorporation of RP at 2% and 8% P enhanced compost biodegradation resulting in a 12% and 22% significantly (P < 0.001) lower final C/N ratio, respectively, compared to the control; together with higher humification parameters. Amending the cow dung – waste paper mixture with 2%, 4% and 8% P as rock phosphate, resulted in a 39%; 50% and 65% more resin extractable P, respectively, relative to the control. Similarly, the bicarbonate extractable P, which represents the bioavailable P fraction, increased consistently by 19%; 28% and 33% following 2%, 4% and 8% RP application, respectively. Though incorporation of RP initially resulted in increased heavy metal levels, reductions of 40%; 35%; 35%; 40% and 45% for Cr, Cu, Cd, Pb and Zn, respectively, were observed in the 8% RP treatment after 8 weeks, due to the presence of earthworms. Vermicomposting with E. fetida significantly reduced heavy metals to levels below the maximum permissible concentration of potentially toxic elements in soils after 8 weeks. This study demonstrates the potential of optimized vermicomposting with igneous RP for generating nutrient rich organic fertilizers.

Plants commonly suffer from phosphorus (P) deficiency in calcareous soils. Plant responses to P application on such soils mostly show poor correlation with their soil test P values. Experiments were conducted on 24 different soil samples under laboratory and greenhouse conditions to illustrate the relationship of various inorganic P fractions in different calcareous soils with P uptake by plants, P extraction by iron‐impregnated filter paper, and P soil test values estimated by 0.5M NaHCO3 and ammonium bicarbonate diethylene triamine penta‐acetic acid. Total P in the 24 soils ranged from 652 to 1245 mgkg−1 with a mean of 922 mgkg−1. A major proportion (98%) of inorganic P was in HCl‐P (Ca‐bound) form. The HCl‐P (Ca‐bound) ranged from 296 to 729 with a mean of 480 mgkg−1. The iron (Fe) and aluminum (Al)‐P (NaOH‐P) ranged from 0.92 to 12 mgkg−1 with a mean of 1.57 mgkg−1. The Fe‐P (citrate‐dithionite bicarbonate) ranged from 0.22 to 4.40 mgkg−1 with a mean of 5.99 mgkg−1. Data regarding P release f...

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing cimetidine are reviewed. According to the current Biopharmaceutics Classification System (BCS), cimetidine would be assigned to Class III. Cimetidine's therapeutic use and therapeutic index, its pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability (BA) problems were also taken into consideration. On the basis of the overall evidence, a biowaiver can be recommended for cimetidine IR products, provided that the test product contains only those excipients reported in this paper in their usual amounts, and that the test and the comparator drug products both are “rapidly dissolving” as per BCS.