Transcript pps
Trends in Solvent Management in the Pharmaceutical Industry
C. Stewart Slater and Mariano J. Savelski
Department of Chemical Engineering Rowan University Glassboro, NJ
Session 656: Green Engineering in the Fine Chemical and Pharmaceutical Industry AIChE Annual Meeting Nashville, TN November 8-13, 2009
Solvent Issues
• • • • • Solvent use can account for up to 80-90% of total mass of an API synthesis – Majority are organic solvents Solvent costs over life cycle – – – Pay to purchase Pay to use (energy and associated costs) Pay to dispose of E-Factor 25->100 kg/kg of API* Not optimal for a ChE!!!
Practice green chemistry & engineering Sheldon,
Chem Ind
,
1
(1997) 12
Pharma Industry Profile
Various other solvents N,N Dimethylformamide n-Butyl alcohol n-Hexane Chloroform Nitrate compounds Hydrochloric acid Acetonitrile Toluene Methanol • • • US EPA Toxic Release Inventory (TRI) 2006 128 MM kg waste Top ten solvents account for 80% of waste Dichloromethane Lopez,
Toxic Release Inventory
, US EPA, 2006
Solvent Waste Management Trends
• • • • • ~70% of waste is treated or recycled* ~30% of waste is used for energy recovery* Only a small percent is directly released into the environment Incineration remains the disposal method of choice – CO 2 – emissions Heat recovery Increasing trend towards solvent recovery Lopez,
Toxic Release Inventory
, US EPA, 2006
Optimization of Solvent Use and Waste Reduction
• • Greener solvent selection / solvent substitution – Elimination of highly hazardous solvents Solvent reduction – – – – – – Recovery techniques Novel approaches to separations Telescoping Novel reaction media (ionic liquids) Biocatalytic routes Solid-state chemistry
“Plant of the Future”
• • • The plant of the future will likely use a limited number of ‘universal’ green solvents – Properties allow for easy recovery – – Used with other campaigns Integrated solvent recovery systems Continuous processing simplifies recovery design strategies Energy exchange networks Slater and Savelski,
Innov Pharma Tech
,
29
(2009) 78
Solvent Recovery
• • • • • Solvent recovery has increased, On-site and Off-site recovery facilities Distillation still dominates - straightforward separation for ideal mixtures Pharmaceutical wastes typically contain – – – Multiple solvents Azeotropic mixtures Unconverted reactants, etc Complex separation trains to obtain high quality solvent for reuse Centralized solvent recovery facility > New approach integrate separation processes at the point of use
Solvent Recovery
• • • Azeotropic separations pose the most 1 challenge in processing 0.9
0.8
Entrainer-based distillation – – More energy intensive Entrainers pose additional source of pollution 0.7
0.6
0.5
0.4
0.3
0.2
0.1
0 0 0.1
0.2
Membrane pervaporation is a “greener” alternative for azeotropic separations 0.3
Wilson Pressure Analysis
0.4
0.5
0.6
Mass Fraction IPA in Liquid
0.7
0.8
0.9
1 760 torr 150 torr 3 bar 10 bar 25 bar 45 deg
Pervaporation Membrane Processes
• • Applications: Selective solvent-water separations / Dehydration Azeotrope separations Water = blue Solvent = green Advantages: Energy savings over distillation No entrainer (e.g., benzene) needed for azeotropic separations Solvent reuse; solvent savings Avoid solvent disposal / solvent thermal oxidation
www.sulzerchemtech.com
PV Process Integration
Solvent-water waste stream Solvent-water azeotropic mixture Pervaporation Dehydrated solvent for reuse Low flow rate stream: water with some solvent • • • • • • • • • • Typical Solvents Isopropanol (az) Ethanol (az) Methanol Ethyl acetate Butyl acetate Acetone Acetronitrile (az) Tetrahydrofuran (az) n-Butanol Methylethylketone (az)
THF Water
No Recovery
THF Water
WASTE
THF Water Green Integration Illustrative Example Process optimization
Extractive Distillation
Emissions reduction Cost savings Energy savings 1,2 Propanediol
RECOVERY
THF Trace water
Pervaporation
RECOVERY
THF Trace Water
WASTE
THF Water
RECOVERY
Water THF
Process Case Study - Pfizer
• • • Investigation of solvent recovery alternatives to reduce solvent waste in celecoxib process IPA / Water Washes 50% IPA 50% Water Recovery IPA / Water Washes IPA solvent recovery from final purification steps Integration of pervaporation with distillation using existing equipment inventory Solvents Water API Other Centrifuge Wet Product Solids 49.2% IPA 49.6% H 0.5% TDS 2 O 0.71% MeOH and EtOH Mother Liquor 34.5% IPA 45.2% H 2 O 8.45% MeOH 2.71% EtOH 9.10% TDS Conc. & Sell ML Celecoxib Dryer Dryer Distillates 50.7% IPA 48.8% H 0% TDS 2 O 0.47% MeOH and EtOH Slater, Savelski, Hounsell, Pilipauskas, Urbanski,
ACS Green Chem & Eng Annual Conf
, Washington DC, June 2008,
Proposed Distillation-PV-Distillation Process
A design basis of 1000 kg waste/hr is used for illustrative purposes Alcohol Waste Second Distillation Celecoxib Waste Vacuum Pump Vacuum Pump IPA Product Initial Distillation Water Waste With TDS • • • Purification for only part of waste stream – Centrifuge wash and Dyer distillates for recovery – Mother liquor for (sale) use as generic solvent Overall 57% IPA recovered @ 99.1 wt% for reuse in process Other options of Distill-PV or PV only, yield different recoveries and purities Slater, Savelski, Hounsell, Pilipauskas, Urbanski,
ACS Green Chem & Eng Annual Conf
, Washington DC, June 2008,
Life Cycle Emissions Comparison
Total Base Case Emissions: 29.5 kg waste/kg API IPA Manufacture 40% Incineration 60% Total Dist-PV-Dist Emissions: 2.4 kg waste/kg API Dist-PV-Dist 22% ML Distillation 19% ~92% decrease in total emissions
Savelski, Slater, Carole, 8 th Inter. Conf. EcoBalance, Tokyo, Japan, December 2008.
IPA Manufacture 59%
Economic Analysis
6,000,000 5,000,000 4,000,000 3,000,000 2,000,000 1,000,000 0 -1,000,000 72% Annual Cost Savings Base Case Distil-PV-Distil-Sell ML
Design Case
ML Concentrate sale Membrane Modules Operating Labor Maintenance Cooling Water Electricity Steam Waste Disposal Fresh IPA Slater, Savelski, Hounsell, Pilipauskas, Urbanski, ACS
Green Chem & Eng Annual Conf
, Washington DC, June 2008,
Summary
•
Solvent use and waste practices should be constantly reviewed
•
Development of sustainable practices
• •
Green advantage
Waste minimization Cost effective
Acknowledgements
• Pfizer • U.S. Environmental Protection Agency P2 grant #NP97257006-0