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LATEST TECHNOLOGY
IN
Safe handling & Recovery
OF
Solvents in Pharma
Industry
TYPICAL SOLVENT USE IN Pharma Industry
Usage of solvents in an API process development is for:
• Diluent to carry out reaction
• To produce high purity product
• Consistent quality of the product
• Higher yields
• Volume efficiency
• Operability• Solvent are used about 80 to 90% of mass
• Solvents are dominant in determining the toxicity of the process
• RISK FACTORS
• Safety• Environmental Impact
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Solvent use
DEVELOPMENT STAGE
Scientist have to considerSolubility – selection basis.
� Polarity – refers to s separation of electric charge.
� Volatility – tendency to vaporize at different temperatures.
� Cost and easy availability.
� Melting/Boiling points.
� Viscosity- resistance of a fluid.
� Flash Point
� Corrosiveness.
� Reactivity.
� Environmental health and safety
SAFETY
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Green chemistry solvent guide
Preferred
� Water
� Acetone
� Ethanol
� 2-Propanol
� 1-Propanol
� Ethyl acetate
� Isopropyl acetate
� Methanol
� MEA
� 1-Butanol
� t-Butanol
Usable
� Cyclohexane
� Heptanes
� Toluene
� t-Butyl Methyl ether
� Isooctane
� Acetonitrile
� 2-MeTHF
� Xylenes
� DMSO
� Acetic acid
� Ethylene Glycol
Undesirable
� Pentane
� Hexane's
� Di-Isopropyl ether
� Di-ethyl ether
� Dichloromethane
� Chloroform
� Dichloroethane
� DMF
� N-Methyl pyrolidine
� Pyridine
� Di methyl acetamide
� Dioxane
� Di methoxy ethane
� Benzene
� Carbon Tetra chloride.
SOLVENT IMPACT
Solvent forms a major role in API
– Cost
– Safety & Hazard
– Handling & storage
– Utility consumption
– Environmental Impact
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ECONOMY
Consumption of 2000 Lts per batch for 10 batch a month
Reduction by 5%
Recovery improvement by 10%
Will save
Rs 3.0 Lakhs per month for a 10 batch/month operation directly
(reduction, steam cost & recovery improvement)
The saving in manpower, storage, handling and environment is bonus.
Solvent reduction methods
• Choosing right solvent- reduce multiple solvent
handling.
• Combine steps of reaction to reduce solvent use -
Telescoping.
• Process loss by better handling
• Wash and reuse where ever possible
• Recover and recycle where ever possible.
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Optimization of Solvent Use
• Greener solvent selection & substitution
• Reduce solvents carbon footprint
• Elimination of highly hazardous solvents
• Solvent reduction
• Recovery techniques
• Novel approaches to separations
• Novel reaction media (ionic liquids)
• Solid-state chemistry
• Bio catalytic routes
Solvent recovery methods
• Wash and reuse.
• Simple boil over and reuse.
• Distill and purify – binary/ azeotropic
/fractional (atmospheric/pressure or
vacuum)
• Per vaporation techniques
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SAFE HANDLING
• Close loop hamdling and avoid mannual and drum
handling.
• Proper earthing while handling
• Avoid flexible piping and use hard pipes.
• Do not charge solvent into hot reactors/systems.
• Keep the condenser temperatures within control and
monitor them periodically.
• Store solvent in cool and dry place.
Solvent Recovery Improvements
• Better utility and design of the distillation system.
• High vacuum distillation– better recovery , yield and purity of the product – key factors- Joints, vacuum system.
• Use of vent condenser in Reactors.
• De scaling frequently of the heat exchangers and reactor jackets.
• Use of molecular sieve for removal of moisture.
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Per vaporation methods
• Is only membrane process where phase transition occurs.
• The heat of vaporization has to be supplied.
• The mass transport is achieved lowering the activity of the permeating component on the permeate side by: gas carrier, vacuum or temperature difference.
• The driving force is the partial pressure difference of the permeate between the feed and permeate streams.
• The permeate pressure has to be lower than the saturation pressure of the permeant to achieve the separation.
Gas carrier Pervaporation
Vacuum Pervaporation
Temperature difference
Pervaporation
Figure 2. Schematic draws of pervaporation processes.
Per vaporation Applications
Usually used for the chemical process industry, but there are other areas of application
� Food.� Farmaceutical industries� Enviromental problem� Analytical application
Since there are many applications a classification that can be useful is given below:
Aqueous mixtures
• Removal of water from organic solvents.
• Alcohols from fermentation broths (ethanol, butanol, etc..)
• Volatile organic contaminants from waste water (aromatics, chlorinated hydrocarbons)
• Removal of flavor and aroma compounds.
• Removal of phenolic compounds.
Non-aqueous mixtures
• Alcohols/aromatics (methanol/toluene)
• Alcohols/aliphatics (ethanol/hexane)
• Alcohols/ethers (Methanol/MTBE)
• Cyclohexane/benzene
• Hexane/toluene.
• Butane/butene.
• C-8 isomers (o-xylene, m-xylene, p-xylene, styrene).
{{
Volatile organic compounds from water
Dehydration
}}
Polar/Non polar
Aromatics/Aliphatic}}Saturated/Unsaturated
Isomers
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Mechanism of Transport
• Pervaporation involve a sequence of three steps:
• Selective sorption
• Selective diffusion through the membrane.
• Desorption into a vapor phase on the permeate side.
Because of its characteristics, pervaporation is often mistakenly considered as a kind of extractive distillation but VLE ≠ Solution-Diffution mechanism.
Figure 3. Comparison between VLE and pervaporation
Summary Per vaporation
Advantages
� Low energy consumption.
� Low investment cost.
� Better selectivity without thermodynamic limitations.
� Clean and close operation.
� No process wastes.
� Compact and scalable units.
Drawback
� Scarce membrane market.
� Lack of information.
� Low permeate flows.
� Better selectivity without thermodynamic limitations.
� Limited applications:
� Organic substances dehydration.
� Recovery of volatile compounds at low concentrations.
� Separation of azeo tropic mixtures.
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Summary Per vaporation
Membranes: Composite membranes with an
elastomeric or glassy polymeric top layer.
Thickness: ≈ 0.1 to few µm (for top layer)
Pore size: Non-porous
Driven force: Partial vapor pressure or activity
difference.
Separation principle: Solution/Diffusion
Membrane material: Elastomeric and glassy.
Applications: � Dehydration of organic solvents.
� Removal of organic compounds from
water.
� Polar/non-polar.
� Saturated/unsaturated.
� Separation of isomers.