Mariano J. Savelski

On zero water discharge solutions in the process industry

Abstract This paper presents a mathematical programming approach to analyze the feasibility of zero liquid discharge option in different industries. Mathematical programming methodologies are applied to four industrial cases—a tricresyl phosphate plant, an ethyl chloride plant, a paper mill and a refinery. In each case study various end of pipe and regeneration configurations using different treatment technologies are explored to determine the possibility of zero liquid discharge and its economical feasibility. The results show that the relationship between the cost of regeneration and the cost of freshwater as well as the discharge concentration of the treatment is the determining factor for the feasibility of zero liquid discharge.

LCA approach to the analysis of solvent waste issues in the pharmaceutical industry

Life cycle assessment offers a unique opportunity to analyze emission reductions across all manufacturing sectors. However, few efforts have been made to apply this method to the pharmaceutical industry. Typically, between 80 and 90% of the total mass used in the production of an active pharmaceutical ingredient (API) may be attributed to solvent use. Manufacture of virgin solvent and solvent waste management contribute significantly more life cycle emissions than comparable processes for commodity chemicals, with the majority of this waste consisting of CO2 and other green house gas emissions. Three case studies from Pfizer, Bristol-Myers Squibb, and Novartis are examined. In these cases, solvent recovery and reduction techniques are integrated into API syntheses. It is shown that the actual extent of the environmental footprint reduction can only be realized with a full life cycle analysis.

A method to characterize the greenness of solvents used in pharmaceutical manufacture

This paper describes the development of a method to calculate the overall “greenness” of a pharmaceutical process that uses multiple solvents. This calculation is made by taking into account various environmental parameters and determining an overall greenness index. Through this method a scientist or engineer can effectively determine alternative, “greener” solvents or processes based on the use of a solvent database and greenness score. The objective is to develop a means to improve the process of drug development through solvent replacement/reduction. A solvent selection table, using a common spreadsheet software routine, was developed for the purpose of allowing a user to compare the greenness between two different process routes. This table includes over 60 solvents and associated chemicals common in the pharmaceutical and chemical industries. The comparison was made possible by the creation of a user-defined, weighted-solvent, greenness index that is an overall weighted factor taking into consideration solvent type, quantity used, and environmental impact. A given process or solvent receives an index ranking based on a variety of environmental and health parameters. The index values, along with the mass of solvents used in the given process, are used to compute the index, which allows for a quick and easy quantitative environmental comparison between two potential process routes.

Pervaporation as a green drying process for tetrahydrofuran recovery in pharmaceutical synthesis

The use of pervaporation technology as a green drying process for the recovery and reuse of the solvent, tetrahyrdofuran, in a pharmaceutical synthesis has been evaluated. A case study has been performed on a step in the synthesis of a new oncology drug. Pervaporation has been integrated with a constant-volume distillation process to produce a hybrid system that allows for the recovery and reuse of tetrahydrofuran. An economic and environmental analysis shows that this is an effective technology for this application.

Pervaporation study for the dehydration of tetrahydrofuran-water mixtures by polymeric and ceramic membranes

Pervaporation technology can effectively separate a tetrahydrofuran (THF) solvent-water waste stream at an azeotropic concentration. The performance of a Sulzer® 2210 polyvinyl alcohol (PVA) membrane and a Pervatech BV® silica membrane were studied, as the operating variables feed temperature and permeate pressure, were varied. The silica membrane was found to exhibit a flux of almost double that of the PVA membrane, but both membranes had comparable separation ability in purifying the solvent-water mixture. At benchmark feed conditions of 96 wt% THF and 4 wt% water, 50°C and 10 torr permeate pressure, the silica membrane flux was 0.276 kg/m2hr and selectivity was 365. For both membranes, flux was found to increase at an exponential rate as the feed temperature increased from 20 to 60°C. The flux through the silica membrane increases at a 6% faster rate than the PVA membrane. Flux decreased as permeate pressure was increased from 5 to 25 torr for both membranes. The amount of water in the permeate decreased exponentially as the permeate pressure was increased, but increased linearly with increasing temperature. Optimum conditions for flux and selectivity are at low permeate pressure and high feed temperature. When a small amount of salt is added to the feed solution, an increase in flux is observed. Overall models for flux and permeate concentration were created from the experimental data. The models were used to predict scale-up performance in separating an azeotropic feed waste to produce dehydrated THF solvent for reuse and a permeate stream with a dilute THF concentration.

Green design alternatives for isopropanol recovery in the celecoxib process

Various approaches to solvent recovery have been studied for the manufacturing process of celecoxib, the active ingredient in Celebrex®. A design case study has been performed by Rowan University with Pfizer through a green engineering partnership program. The manufacturing operation at one of their plants was evaluated and several green engineering alternatives for the purification and recovery of isopropanol (IPA) from waste streams proposed. This separation is complex due to the multiple waste streams generated, with varying compositions of IPA, ethanol, methanol, water, and dissolved solids. Overall goals were waste minimization and IPA recovery and purification. A conceptual study of distillation, extraction, reactive distillation, adsorption, and membrane-based processes was performed. Through use of computer simulation and literature/design methodologies, traditional methods were shown to be unable to obtain high IPA purities with the available equipment. Several green design approaches were evaluated using distillation combined with either molecular sieve adsorption or membrane pervaporation. These process schemes appear to have the most promise to effectively recover and purify IPA. The case study describes equipment and processing issues, and estimates environmental impacts from a life cycle analysis.

Environmental analysis of the life cycle emissions of 2-methyl tetrahydrofuran solvent manufactured from renewable resources.

ABSTRACT An environmental analysis has been conducted to determine the cradle to gate life cycle emissions to manufacture the green solvent, 2-methyl tetrahydrofuran. The solvent is considered a greener chemical since it can be manufactured from renewable resources with a lower life cycle footprint. Analyses have been performed using different methods to show greenness in both its production and industrial use. This solvent can potentially be substituted for other ether and chlorinated solvents commonly used in organometallic and biphasic reactions steps in pharmaceutical and fine chemical syntheses. The 2-methyl tetrahydrofuran made from renewable agricultural by-products is marketed by Penn A Kem under the name ecoMeTHF™. The starting material, 2-furfuraldehyde (furfural), is produced from corn cob waste by converting the available pentosans by acid hydrolysis. An evaluation of each step in the process was necessary to determine the overall life cycle and specific CO2 emissions for each raw material/intermediate produced. Allocation of credits for CO2 from the incineration of solvents made from renewable feedstocks significantly reduced the overall carbon footprint. Using this approach, the overall life cycle emissions for production of 1 kg of ecoMeTHF™ were determined to be 0.191 kg, including 0.150 kg of CO2. Life cycle emissions generated from raw material manufacture represents the majority of the overall environmental impact. Our evaluation shows that using 2-methyl tetrahydrofuran in an industrial scenario results in a 97% reduction in emissions, when compared to typically used solvents such as tetrahydrofuran, made through a conventional chemical route.

Life cycle analysis of solvent reduction in pharmaceutical synthesis using continuous adsorption for palladium removal.

The life cycle emissions associated with the reduction of wastes from an adsorption process to remove palladium complexes in drug manufacture have been evaluated. The study assessed a green improvement to a process step in an active pharmaceutical ingredient synthesis where palladium catalyst is removed from a reaction mixture. The greener process uses a continuous adsorption system, composed of a more efficient adsorbent, consuming less organic solvent and rinse water, which results in less waste disposal. The newer process is also more energy and cost efficient from an operational perspective. There is a 94% reduction in the carbon footprint of the new process when compared to the current operation.

Life cycle assessment of solvent extraction as a low-energy alternative to distillation for recovery of N-methyl-2-pyrrolidone from process waste

Abstract This case study investigates low-energy alternatives to distillation for the recovery of N-methyl-2-pyrrolidone (NMP) from solvent waste in the manufacture of resin precursors. Evaluation includes environmental and economic life cycle assessment of solvent recovery and reuse using batch distillation, solvent extraction, and solvent extraction at a sister plant. Solvent extraction at the sister plant involved shipment of hazardous waste to a facility with existing solvent recovery equipment and lower purity standards for NMP. The amount of processing required to recover useful NMP is reduced, increasing reductions in life cycle emissions and damages to the environment. Extraction at the sister plant recovered 98% of the NMP at a purity of 97.1 wt% from aqueous waste containing 17 wt% NMP. Extraction at the sister plant reduced total and CO2 life cycle emissions by 61% and 59%, respectively. Compared to the distillation recovery alternative, extraction at the sister plant results in reductions of 32% and 33% for total and CO2 life cycle emissions, respectively. Annual operating costs were reduced by 80%, with no capital investment, due to utilization of existing equipment. This resulted in a 10-year net present value (NPV) of

Dynamic vibratory membrane processing for use in water recovery from soluble coffee product manufacturing wastewater

4.20 million, whereas distillation resulted in a 10-year NPV of