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Use of Life Cycle Assessment in Evaluating Solvent Recovery Alternatives
in Pharmaceutical Manufacture
William A. Carole, C. Stewart Slater, Mariano J. Savelski*, Timothy Moroz, Anthony Furiato, Kyle Lynch Rowan University, Dept. of Chemical Engineering 201 Mullica Hill Rd., Glassboro, NJ 08028, USA Keywords: pharmaceutical manufacture, solvent recovery, pervaporation, life cycle assessment
ABSTRACT
A retrofit case study is presented in this paper to compare various treatment options of pharmaceutical wastes generated in the manufacturing of celecoxib. Celecoxib is the active pharmaceutical ingredient in Celebrex®, an arthritis pain medicine produced by Pfizer, Inc. Each proposed treatment method was evaluated based on its ability to efficiently separate and purify isopropyl alcohol (IPA) from an aqueous waste stream. A pervaporation-distillation hybrid process was identified technically feasible to treat the wastes and to recycle IPA back into the process. The recovery of the spent IPA avoids its incineration and also reduces the inventory of fresh IPA required to operate the celecoxib process. Life cycle inventories have been generated to quantify the environmental performance of each treatment option. A life cycle assessment was then conducted to determine the percent reduction of emissions for each alternative as compared to the base case. It was found that the treatment of all the waste by a combination of pervaporation-distillation and conventional methods can reduce emissions by 92%. OBJECTIVE
University, several green solvent recovery methods were A case study was developed to measure the proposed as alternatives to waste incineration. This project environmental performance of several green solvent is supported by the U.S. Environmental Protection Agency recovery alternatives to minimize the wastes produced in and Pfizer Green Chemistry Program. The addition of a the celecoxib process [1]. Each recovery alternative was solvent recovery system would reduce the amount of fresh evaluated to determine their ability to efficiently separate IPA required for the celecoxib process. This would lower and recover IPA form an aqueous waste stream. This can the environmental footprint for the production of celecoxib prove to be a difficult separation as IPA forms an azeotrope by avoiding the manufacturing of fresh IPA and reducing with water at 12 wt. % which is not pressure sensitive. A life cycle inventory was generated for the recovery methods which were able to effectively separate and purify IPA E-Factor = 9.0
from the process waste streams. A life cycle assessment was later conducted to measure the environmental performance of each recovery technique as compared to the INTRODUCTION
Celebrex® is an arthritis pain medicine which is produced by Pfizer, Inc. The process used to produce the active pharmaceutical ingredient, celecoxib, was found to be very mass efficient with an E-factor of only 9. Typical E-factors for pharmaceutical processes have been estimated to range from 25 to more than 100 kg waste / kg API [2]. The basic process used to manufacture celecoxib at the Pfizer plant in Barceloneta, Puerto Rico is shown in Fig.1 Since the production of celecoxib is relatively large, the recovery of the waste streams was thought to provide substantial economic and environmental benefits. In a cooperative effort between Pfizer, Inc. and Rowan Fig. 1 General celecoxib process flow diagram [3]
CASE STUDY
solvent. The main advantage to this solvent recovery Initially, each recovery alternative was modeled system is that the equipment necessary to operate it is to determine if it could be used to efficiently separate a available at the production site. Therefore, the use of a combined IPA/water waste stream. A pressure-swing hybrid distillation-PV system was also considered to be a distillation recovery system was the first proposed feasible alternative to the incineration of the process wastes. alternative to waste incineration. When treating a combined waste stream from the celecoxib process, an IPA purity of only 75% was obtained using this method. If the dryer ENVIRONMENTAL ANALYSIS
distillate and centrifuge washes are treated without the Since the distillation-MS, distillation-PV, and mother liquor, the IPA purity increases to 86%. Additional distillation-PV-distillation processes proved to be highly studies showed that the IPA/water azeotrope was not efficient at separating the IPA/water waste streams, a pressure sensitive. Therefore the pressure-swing distillation LCI/A was performed on each. SimaPro 7.1 (PRé system was unable to further increase the IPA purity in the Consultants) and Ecosolvent 1.0.1 were used to determine distillate to acceptable levels for it to be recycled back into the LCI for each process step and various waste treatment methods, respectively. As IPA was the main solvent to be An extractive distillation solvent recovery recovered, the LCI was generated on that, neglecting the process was also modeled. Extractive distillation involves manufacture or disposal of water and other feed stocks. the addition of an entrainer to extract IPA from water at its For each recovery method, only the dryer azeotropic concentration. Diisopropyl ether, ethylene glycol, distillates and centrifuge washes were treated. The mother and dimethyl sulfoxide were identified as possible liquor was either incinerated or concentrated and sold as a entrainers to recover IPA. The use of diisopropyl ether was generic solvent. If the mother liquor is sold as a generic able to produce a 99% pure IPA product but required that solvent, then it is assumed that its manufacture is avoided the column operate at 30 atm. Ethylene glycol and dimethyl when generating the LCI’s. Depending on whether the sulfoxide produced 94% and 99% pure IPA product mother liquor is incinerated or sold, the life cycle block streams, respectively; however, multiple columns were flow diagram (BFD) differs slightly, as shown in Fig.2 and needed. The extreme operating conditions that extractive distillation would require were found to surpass the Using SimaPro 7.1, the total emissions, energy equipment limitations at the Barceloneta site and were not and mass utilization for each solvent recovery alternative was quantified. Fig.4 displays the percent reduction in both Both molecular sieves (MS) and pervaporation total emissions and CO2 emissions from the use of either (PV) systems were considered as possible solvent recovery membrane-based recovery system when compared to the alternatives. In both cases distillation is used to bring the waste stream composition to the azeotropic concentration According to Fig.4, the total process emissions and then followed by either MS or PV systems. When are lowered by 64 – 96% depending on the recovery modeling a distillation-MS process, an IPA product stream method chosen. It was also determined that selling the of 99.5% purity was obtained. This was achieved through mother liquor instead of incinerating it reduced the total the use of a dual MS system to allow for regeneration emissions by an additional 75 – 80%. The large reduction cycles. The high IPA purity would allow it to be directly recycled back into the celecoxib process making a distillation-MS recovery system a feasible alternative to incineration. However, it was estimated that a $1.5 MM capital investment would be required to purchase and install the MS units at the Barceloneta site as they are not A common distillation-pervaporation hybrid process was also considered. It was determined that by sending the vapor distillates from a distillation column through a PV system, a 98.4% pure IPA product could be produced based on the capacity of the existing PV units at the Barceloneta site. The addition of a second distillation column following the PV unit further purified the IPA to 99.1%. These results were achieved by treating the dryer Fig.2 Life Cycle Block Flow Diagram – Solvent
distillates and centrifuge washes, leaving the mother liquor Recovery Process with Mother Liquor Incinerated
to be incinerated or concentrated and sold as a generic Fig.3 Life Cycle Blo
ck Flow Diagram –
Solvent Recovery Proces
s with Mother Liquor Sold
Fig.4 LCI Percent Reductio
ns from the Base Case [1]
in LCI emissions was primarily due to the recovery and recommended as the best recovery method. The addition of reuse of spent IPA in the celecoxib process. This avoided the distillation-PV-distillation recovery method to the the manufacture and disposal of fresh IPA which was no current celecoxib process required an additional 10,700 kg longer required and reduced the environmental footprint of steam/batch, 59 kWh electricity/batch, and 345,230 kg the process. Also, since the mother liquor is considered a cooling water/batch but reduced the total LCI emissions by generic solvent, its sale avoids the manufacture of other 12.6 MM kg per year (91.9% reduction from the base case) generic solvents which further reduces the LCI emissions. and the total CO2 emissions by 11.6 MM kg per year (94.7% reduction from the base case). The cumulative From the life cycle assessment, the use of a energy demand (CED) was also reduced by 202,706 MJ-Eq distillation-PV system where the mother liquor is sold was for a 111% reduction when compared to the base case. The found to have the largest reduction in LCI emissions. use of a distillation-PV-distillation solvent recovery system However, the distillation-PV-distillation configuration was as an alternative to waste incineration therefore increased able to produce IPA at a higher purity with a minimal the overall greenness of the celecoxib process. [1,3] increase in process emissions, and was therefore ECONOMIC ANALYSIS
plant. The authors thank the Pfizer Green Chemistry The base case annual cost for the celecoxib Program and Pfizer Green Chemistry Lead, Dr. Peter Dunn process was $5.28 MM. Approximately 45% of this cost for their support of the Rowan clinic partnership. The resulted from purchasing fresh IPA and the remaining 55% authors also acknowledge the support of the U.S. was due to waste disposal costs. Through the Environmental Protection Agency through the Pollution implementation of a distillation-PV-distillation recovery Prevention grant program (NP97257006-0) and for their process in place of incineration, the total annual operation support of the Rowan projects within the green engineering costs reduced to $1.46 MM for a 72% savings. The pharmaceutical manufacturing initiative. additional polishing column increased the total operating costs by 0.5% when compared to the single distillation-PV REFERENCES
recovery system. However, the additional column was [1] Savelski, M., Slater, C.S., Hounsell G., Pilipauskas, D., required to obtain the desired IPA purity. Since the Urbanski, F., A Collaborative Partnership to Develop majority of the spent IPA recovered in the celecoxib Strategies for Waste Minimization and Solvent Recovery process is now available to be recycled, the costs associated for the Celecoxib Process, 12th Green Chemistry & with purchasing fresh IPA were reduced by 43%. [3] If the Engineering Conference, Washington, DC, June 2008 distillation-MS recovery system was used, the total annual [2] Sheldon, R.A. Chemistry and Industry 1997, Vol.1,
savings would only increase by less than 1% but require a $1.5 MM capital investment [3]. The equipment needed to [3] Slater, C.S., Savelski, M., Hounsell, G., Pilipauskas D., operate the distillation-PV-distillation system is already Urbanski, F., Analysis of Separation Methods for available on-site therefore only new membranes would Isopropanol Recovery in the Celecoxib Process, need to be purchased which are incorporated into the Proceedings of the 2008 Meeting of the American Institute of Chemical Engineers, Philadelphia, PA, November 2008. CONCLUSION
A life cycle assessment was performed for several distillation-membrane based recovery methods to separate and purify IPA from a pharmaceutical waste stream. A distillation-PV-distillation recovery system was found to produce 99.1% pure IPA which can be recovered and directly recycled back into the celecoxib process. The addition of this recovery system to treat the dryer distillates and centrifuge washes reduced the total LCI emissions by 91.9% and the total CO2 emissions by 94.7% assuming the mother liquor was sold as a generic solvent. The CED was also observed to decrease by 202,706 MJ-Eq (111% reduction from base case). Thus the proposed IPA recovery system led to a much greener process. distillation-PV-distillation solvent recovery system reduced the annual celecoxib manufacturing costs by $3.8 MM for a 72% savings when compared to the base case. This resulted from a 43% decrease in the cost to purchase fresh IPA and reduced waste disposal costs in the celecoxib process as none of the wastes are incinerated. Since the equipment necessary to operate the distillation-PV-distillation recovery system is available on-site, no capital investments would be required. Therefore the distillation-PV-distillation recovery method is recommended as the best engineering alternative to waste incineration and provides significant environmental and economic benefits. ACKNOWLEDGEMENTS
The authors acknowledge the help and guidance provided by Mr. Jorge Belgodere of the Pfizer Barceloneta

Source: http://sun00.rowan.edu/~savelski/researchpapers/LCA-Tokyo-2008.pdf

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