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Solvent use accounts for 80-90% of mass utilized in a typical Pharmaceutical operation.

In production of APIsIn formulation processIn almost every step right from synthesis to the finished product

PHARMACEUTICAL SOLVENTS

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Class 1 Residual Solvents: Solvents to be AvoidedKnown human carcinogensStrongly suspected human carcinogensEnvironmental hazards

Class 2 Residual Solvents: Solvents to be LimitedNongenotoxic animal carcinogens or possiblecausative agents of other irreversibletoxicity, such as neurotoxicity or teratogenicity.Solvents suspected of other significant but reversibletoxicities.

Class 3 Residual Solvents: Solvents with Low Toxic PotentialSolvents with low toxic potential to humans; nohealth-based exposure limit is needed.[NOTE—Class 3 residual solvents may have PDEs of up to50 mg or more per day.]*

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Class I solvents : should be avoided

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Class 2 solvents: solvents to be limited

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Class 3 solvents: solvents with low toxic potential

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Class 4 solvents: no adequate toxicological data was found

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According to the U.S. Environmental Protection Agency (EPA), pharmaceutical companies generated 530 million tons of toxic waste in 2005; 90% of which was produced by the 20 solvents listed below:• Methanol• Dichloromethane (DCM)• Formaldehyde• Toluene• Acetonitile (ACN)• Hexane• Isopropanol Alcohol (IPA)• n-Butyl Alcohol• Methyl tert-butyl ether (MTBE)• Xylene• Trichloroethane (TCE)• Ethanol• Tetrahydrofuran (THF)

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Supercritical fluids

Ionic liquidsWater

We desire eco friendly solventsOr

Solvent recoveryOr

No solvent at all!!

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Examples:Merck & Co – JANUVIA- Sitagliptin- Initially 270kg waste/kg of API- Redesigned- 50kg waste- solvent consumption reduced.

Pfizer- Antidepressant ZOLOFT- substituted THF, toluene, hexane, CH2Cl2 with hexanePfizer- LIPITOR- 65% reduction in total organic waste by changing manufacturing process.

Bristol Mayers Squibb- PACLITAXEL- pacific yew tree- 11step solvent extraction process- Now replaced with plant cell fermentation of yew cells- eliminated use of organic solvents.