Environmental resource footprinting of drug manufacturing: Effects of scale-up and tablet dosage

The formulation and scale-up of batch processes is one of the major challenges in the development of pharmaceutical dosage forms and at the same time a significant resource demanding process which is generally overlooked in environmental sustainability assessments. First, this paper proposes general trends in the experience curve of cumulative resource consumption of pharmaceutical tablet manufacturing of PREZISTA^® 800 mg through wet granulation (WG) at four consecutive scales in both R&D and manufacturing environments (resp. WG1 = 1 kg/h, WG5 = 5 kg/h, WG30 = 30 kg/h and WG240 = 240 kg/h). Second, the authors aim at evaluating the environmental impact from a life cycle perspective of a daily consumption of PREZISTA^® 2× 400 mg tablets versus the bioequivalent PREZISTA^® 800 mg tablet which was launched to enhance patient compliance. Environmental sustainability assessment was conducted at three different system boundaries, which enables identification, localization and eventually reduction of burdens, in this case natural resource extraction. Exergy Analysis (EA) was used at process level (α) and plant level (β) while a cradle-to-gate Exergetic Life Cycle Assessment (ELCA) was conducted at the overall industrial level (γ) by means of the CEENE method (Cumulative Exergy Extraction from the Natural Environment). Life cycle stages taken into account are Active Pharmaceutical Ingredient (API) production, Drug Product (DP) production and Packaging. At process level (α), the total resource extraction for the manufacturing of one daily dose of PREZISTA^® (800 mg tablet) amounted up to 0.44 MJ_ex at the smallest scale (WG1) while this amount proved to be reduced by 58%, 79% and 83% at WG5, WG30 and WG240 respectively. Expanding the boundaries to the overall industrial level (γ) reveals that the main resource demand is at the production of the Active Pharmaceutical Ingredient (API), excipients, packaging materials and cleaning media used in DP production. At the largest scale (WG240) the use of cleaning media during DP production contributes considerably less to the total resource extraction. Overall, the effect of scale-up and learning on resource consumption during DP production showed to possess a power-law experience curve y = 2.40 * x^−0.57 when shifting from WG1 (smallest lab scale) to WG240 (industrial manufacturing). Tablet dosage (2× 400 mg versus 1× 800 mg) did not significantly affect the absolute environmental burden. However, the relative contribution of resource categories did change due to the different production technology. It could be concluded that in meeting social and economic demands by launching the PREZISTA^® 800 mg tablet, no trade-off in environmental burden occurred. On the long term, future research should strive to take into account R&D processes and all services related to pipeline activities taking place prior to market launch and eventually to allocate impacts to the final product.     

System dynamics model for analyzing effects of eco-design policy on packaging waste management system

EU's long-term objective is to become a recycling and resource effective society, where waste is utilized as a resource and waste generation is prevented. A system dynamics model was developed to analyze the policy mechanisms that promote packaging material efficiency in products through increased recycling rates. The model includes economic incentives such as packaging and landfill taxes combined with market mechanisms, behavioral aspects and ecological considerations in terms of material efficiency (the packaging material per product unit, recycled fraction in products). The paper presents the results of application of various policy instruments for increasing packaging material efficiency and recovery rate and reducing landfilled fraction. The results show that a packaging tax is an effective policy instrument for increasing the material efficiency. It ensures the decrease of the total consumption of materials and subsequent waste generation. The tax helps to counteract a rebound effect, which, as identified by the analysis, can be caused by reduced material costs due to eco-design. The model is applied to the case of Latvia. Yet, the elements and structure of the model developed are similar to waste management systems in many countries. By changing numeric values of certain parameters, the model can be applied to analyze policy mechanisms in other countries.     

秸秆还田下氮肥用量对玉米产量及土壤无机氮的影响

研究连续2年秸秆还田下氮肥用量对玉米产量、氮肥利用率及土壤硝态氮的影响,结果表明,玉米产量随着施氮量的增加逐渐增加,施氮量达到216 kg·hm^-2时,产量最高,施氮量超过216 kg·hm^-2时产量有降低的趋势。相同施氮处理玉米产量年际变化明显,2010年较2009年产量提高0.69％~4.75％。氮肥利用率、氮肥农学利用率和氮收获指数随着秸秆还田年限的增加,均有不同程度的增加。2年0~100 cm土层土壤硝态氮含量均以施氮240 kg·hm^-2最高,且有向土壤深层迁移的趋势,对浅层地下水构成潜在的威胁。与施氮240 kg·hm^-2相比,施氮168、192 kg·hm^-2和216 kg·hm^-2处理0~100 cm土壤无机氮残留量2年平均减少39.87％、35.84％和29.38％。相同施氮处理,0~100 cm土壤无机氮累积量2010年较2009年略有降低。综合考虑玉米产量、氮肥利用率与生态环境效益,该地区最适施氮量200 kg·hm^-2左右。     

Sorption of 2,4-D on Natural and Organic Amended Soils of Different Characteristics

The effect of one organic amendment consisting of an urban waste compost (UWC) was assessed on the sorption properties of the herbicide 2,4-D on four soils of different physicochemical characteristics. The soils chosen were a Typic Haphorthod (ST), a Typic Endoaquept (SR), an Entic Pelloxerert (TO), and a Typic Eutrochrept (AL). Adsorption experiments were performed on the original soils, and on mixtures of these soils with UWC at a rate of 6.25% (w/w). These mixtures were used just after preparation, and after aging for 8 and 25 weeks. 2,4-D adsorption was the highest on ST soil, whereas the lowest adsorption was for SR soil. This behavior is related to the high amount of organic matter (OM) and amorphous iron and aluminum oxides content on soil ST, whereas soil SR had the lowest OM content and specific surface area of the soils of this study. Addition of exogenous OM to soils caused an increase in the 2,4-D adsorption by three of the soils treated with UWC, with the only exception being ST soil, due to an observed decrease in its specific surface area. The adsorbed amounts of the herbicide on aged organic fertilized soils diminished in three of the amended soils, but was still greater than on unamended soils. In contrast, the ST soil showed the largest adsorption for unamended soil.     

Comparison of a two-stage sampling design and its composite sample alternative: An application to soil studies

The objective of a long-term soil survey is to determine the mean concentrations of several chemical parameters for the pre-defined soil layers and to compare them with the corresponding values in the past. A two-stage random sampling procedure is used to achieve this goal. In the first step, n subplots are selected from N subplots by simple random sampling without replacement; in the second step, m sampling sites are chosen within each of the n selected subplots. Thus n · m soil samples are collected for each soil layer. The idea of the composite sample design comes from the challenge of reducing very expensive laboratory analyses: m laboratory samples from one subplot and one soil layer are physically mixed to form a composite sample. From each of the n selected subplots, one composite sample per soil layer is analyzed in the laboratory, thus n per soil layer in total. In this paper we show that the cost is reduced by the factor m — 1 when instead of the two-stage sampling its composite sample alternative is used; however, the variance of the composite sample mean is increased. In the case of positive intraclass correlation the increase is less than 12.5%; in the case of negative intraclass correlation the increase depends on the properties of the variable as well. For the univariate case we derive the optimal number of subplots and sampling sites. A case study is discussed at the end.     

Evaluation of Saccharomyces cerevisiae strains as probiotic agent with aflatoxin B1 adsorption ability for use in poultry feedstuffs

In this study the aflatoxin B₁ (AFB₁) removal capacity, the tolerance to salivary and gastrointestinal conditions, autoaggregation and coaggregation with pathogenic bacteria of Saccharomyces cerevisiae strains isolated from broiler feces, were evaluated. Only four of twelve isolated strains were identified as Saccharomyces cerevisiae using molecular techniques. The results obtained in AFB₁ binding studies indicated that the amount of AFB₁ removed was both strain and mycotoxin-concentration dependent. Therefore, a theoretical model was applied in order to select the most efficient strain to remove AFB₁ in a wide range of mycotoxin concentration. The results indicated that S. cerevisiae 08 and S. cerevisiae 01 strains were the most efficient microorganisms in the mycotoxin removal. Viability on simulated salivary and gastrointestinal conditions was investigated and S. cerevisiae 08 strain showed the best results, achieving 98% of total survival whereas S. cerevisiae 01 reached only 75%. Autoaggregation and coaggregation assays showed S. cerevisiae 08 as the most appropriate strain, mainly because it was the unique strain able to coaggregate with the four bacterial pathogens assayed. Consequently, S. cerevisiae 08 is the best candidate for future in vivo studies useful to prevent aflatoxicosis. Further quantitative in vitro and in vivo studies are required to evaluate the real impact of yeast-binding activity on the bioavailability of AFB₁ in poultry. However, this study could be useful in selecting efficient strains in terms of AFB₁ binding and provide an important contribution to research into microorganisms with potential probiotic effects on the host.     

Heavy-metal adsorption by non-living biomass

The adsorption of some heavy metals onto the walls of harvested, washed, and dried non-living biomass cells of different Pseudomonas strains was studied at optimum experimental conditions using a simplified single component system. The Langmuir adsorption model was found to be a suitable approach to describe the system via multi-step processes. Isotherms measured at 30.0°C and pH 5.5 with [M]_total = 10-100 mM for tight, reversible Cr⁶⁺(aq), Ni²⁺(aq), Cu²⁺(aq) and Cd²⁺(aq) binding by the cell walls of the investigated biomass fit the Langmuir model and give the pH-independent stoichiometric site capacities ν_i and equilibrium constants K_i for metal binding at specific biomass sites i = A, B, C, and D. Tight binding sites A, B, and D of the non-living biomass are occupied by Cr^VI, sites A and C by Ni^II, sites A and D by Cd^II, and only site B by Cu^II. It is concluded that ν_i is a stoichiometric parameter that is independent of the magnitude of K_i for binding site i and that the studied heavy metals selectively and tightly bind at different biomass sites.     

Innovative policy practices to advance building energy efficiency and retrofitting: Approaches,impacts and challenges in ten C40 cities

This study examines ten programmes to advance energy efficiency and retrofitting of existing, private sector buildings in C40 cities in Asia-Pacific and USA. We set out to identify differing policy approaches, together with potential impacts and implementation challenges for each. Findings unearthed six policy models – both mandatory and voluntary – with unique impacts and challenges. We demonstrate that innovation occurs without new policy inventions and largely by necessity, as new features are added and generic models are adapted to local circumstances. Our sample demonstrated experimentation with benchmarking in the USA, comprehensive regulation in Asia, and voluntary approaches in Australia. Overall, environmental impacts are particularly slow to emerge and plagued with attribution challenges. We found limited evidence of benchmarking programme effectiveness in reducing energy consumption in the short-term, but some indication of mid-term outcomes. Driven by unique local circumstances, the cap-and-trade model stood out by fostering large, sustained and attributable GHG emission reductions and retrofitting. Market and social impacts are highly significant across all programmes, highlighting needs to consider non-environmental impacts in policy evaluation. We emphasise the complementary potential of voluntary and regulatory approaches to advancing energy efficiency and climate resilience. We also underscore the potential for reporting or benchmarking programmes to later transition to models mandating performance improvements, such as cap-and-trade.     

Microbial biomass yield and turnover in soil biodegradation tests: carbon substrate effects

Most of the standardized biodegradation tests used to assess the ultimate biodegradation of environmentally degradable polymers are based solely on the determination of net evolved carbon dioxide. However, under aerobic conditions, it has to be considered that heterotrophic microbial consortia metabolize carbon substrates both to carbon dioxide and in the production of new cell biomass. It is generally accepted that in the relatively short term, 50% of the carbon content of most organic substrates is converted to CO₂, with the remaining carbon being assimilated as biomass or incorporated into humus. The latter is particularly important when the metabolism of the organic matter occurs in a soil environment. A straightforward relationship between the free-energy content of a carbon substrate (expressed as the standard free-energy of combustion) and its propensity for conversion to new microbial biomass rather than mineralization to CO₂ has been established. This can potentially lead to underestimation of biodegradation levels of test compounds, especially when they consist of carbon in a fairly low formal oxidation state and relatively high free-energy content. In the present work, the metabolism of different kind of carbon substrates, especially in soil, is reviewed and compared with our own experimental results from respirometric tests. The results show that conversion of highly oxidized materials, such as the commonly used reference materials, cellulose or starch, to CO₂ may be significantly overestimated. The addition of glucosidic material to soil leads to greatly increased respiration and is accompanied by a very low conversion to biomass or humic substances. In contrast, relatively less oxidized substrates metabolize more slowly to give both CO₂ and biomass to an extent which may be significantly underestimated if glucosidic materials are used as the reference. The need for an overall carbon balance taking into account both the carbon immobilized as biomass and that volatized as CO₂ must be considered in standard respirometric procedures for assessing the biodegradability of slowly degrading macromolecules.     

Energy metabolism and growth of Monoporeia affinis Lindstr. in the Northern Lake Krivoe (Karelia)

The physiological method for estimating production based on the relationship between growth and energy metabolism has been used for calculating model growth curves for the amphipod Monoporeia affinis and comparing them with the results of field studies. Calculations demonstrated that the physiological growth curves fit the results of field observations best under certain conditions which have zoological sense: the growth curve should reflect the actual maximum body size of an animal in the given population, the duration of the life cycle, and the time required for reaching the reproductive size.