Number
286-EN
Section
General Section
Use
Sector
Health services
Other
Function
Other
Process
Other
Product category
laboratory chemicals
Pharmaceuticals
Application
Extraction of Active Pharmaceutical Ingridients (APIs)
Abstract
Supercritical Fluid Technology utilizing carbon dioxide is highly suitable for extraction of non-polar and low-polar small compounds. The technology allows for organic solvent free extraction at low temperatures, protecting sensitive agents from processing damage.
Substituted substances
n-Hexane
CAS No. 110-54-3 EC No. 203-777-6 Index No. 601-037-00-0
Chemical group
Hydrocarbon, aliphatic, saturated
Classification: hazard statements
H225 Highly flammable liquid and vapour
H361f Suspected of damaging fertility
H304 May be fatal if swallowed and enters airways
H336 May cause drowsiness or dizziness
H373 May cause damage to organs through prolonged or repeated exposure
H315 Causes skin irritation
H411 Toxic to aquatic life with long lasting effects
Other adverse effects
The substance is: endocrine disruptor (SIN List), neurotoxic cat. 3 (Vela et al.) as listed in the Substance Database according to SUBSPORT Screening Criteria (SDSC).
Dichloromethane
CAS No. 75-09-2 EC No. 200-838-9 Index No. 602-004-00-3
Chemical group
Chlorinated Halocarbons
Classification: hazard statements
H351 Suspected of causing cancer
Other adverse effects
The substance is: 2B carcinogen (IARC) as listed in the Substance Database according to SUBSPORT Screening Criteria (SDSC).
Chloroform
CAS No. 67-66-3 EC No. 200-663-8 Index No. 602-006-00-4
Chemical group
Chloroalkanes
Classification: hazard statements
H351 Suspected of causing cancer
H361d Suspected of damaging the unborn child
H331 Toxic if inhaled
H302 Harmful if swallowed
H372 Causes damage to organs through prolonged or repeated exposure
H315 Causes skin irritation
H319 Causes serious eye irritation
Other adverse effects
The substance is: 2B carcinogen (IARC), as listed in the Substance Database according to SUBSPORT Screening Criteria (SDSC).
Diethylether
CAS No. 60-29-7 EC No. 200-467-2 Index No. 603-022-00-4
Chemical group
Ether
Classification: hazard statements
H224 Extremely flammable liquid and vapour
H302 Harmful if swallowed
H336 May cause drowsiness or dizziness
Toluene
CAS No. 108-88-3 EC No. 203-625-9 Index No. 601-021-00-3
Chemical group
Aromatic hydrocarbons
Classification: hazard statements
H225 Highly flammable liquid and vapour
H361d Suspected of damaging the unborn child
H304 May be fatal if swallowed and enters airways
H336 May cause drowsiness or dizziness
H373 May cause damage to organs through prolonged or repeated exposure
H315 Causes skin irritation
Xylene
CAS No. 1330-20-7 EC No. 215-535-7 Index No. 601-022-00-9
Chemical group
Aromatic hydrocarbons
Classification: hazard statements
H226 Flammable liquid and vapour
H332 Harmful if inhaled
H312 Harmful in contact with skin
H315 Causes skin irritation
Alternative Substances
Carbon dioxide
CAS No. 124-38-9 EC No. 204-696-9 Index No.
Chemical group
Carbonyl compounds
Reliability of information
Evidence of implementation: there is evidence that the solution was implemented and in use at time of publication
Internet information: data are from an internet document and only a basic and partial evaluation could be performed
Reason substitution
CMR
physical hazards
skin/respiratory sensitizing
other toxic effects
Hazard Assessment
Substances to be substituted: n-Hexane may be fatal if swallowed and enters airways, is toxic to aquatic life with long lasting effects, is a highly flammable liquid and vapour, is suspected of damaging fertility, may cause damage to organs through prolonged or repeated exposure, causes skin irritation and may cause drowsiness or dizziness. The substance is an endocrine disruptor (SIN List), as listed in the Substance Database according to SUBSPORTplus Screening Criteria (SDSC). Dichloromethane is suspected of causing cancer. Chloroform is toxic if inhaled, causes damage to organs through prolonged or repeated exposure, is harmful if swallowed, causes serious eye irritation, is suspected of causing cancer, is suspected of damaging the unborn child and causes skin irritation. Diethylether is an extremely flammable liquid and vapour, is harmful if swallowed and may cause drowsiness or dizziness. Toluene may be fatal if swallowed and enters airways, is a highly flammable liquid and vapour, is suspected of damaging the unborn child, may cause damage to organs through prolonged or repeated exposure, causes skin irritation and may cause drowsiness or dizziness. Xylene is a flammable liquid and vapour, is harmful in contact with skin, is harmful if inhaled and causes skin irritation. Alternative substance: Carbon dioxide is an asphyxiant in higher concentrations, and high pressure equipment as this type of extraction plant need to be well maintained and monitored. Combined with an appropriate sensor grid and ventilation most potential hazards related to Carbon dioxide extraction plants can be circumvented. Occupational safety regarding potential exposure to organic solvents is omitted.
Description of Substitution
Carbon dioxide is a nonpolar solvent suitable for extraction of non-polar and low-polar compounds up to a molecular weight of approx. 250. Carbon dioxide in its supercritical fluid state is an excellent carrier and allowing for extraction at low temperatures gives the advantage of high quality yields of heat sensitive compounds. Process description: Liquid carbon dioxide from storage is pressurised, heated and transferred to the extractor, where it gets loaded according to adjusted process conditions. A change of these conditions (pressure, temperature) causes precipitation of the dissolved substances in the separation vessels. The now gaseous carbon dioxide is condensed, intermediately stored and recycled. Advantages: • Carbon dioxide is inexpensive, not combustible, not explosive, germicidal, free of bacteria, selective and mobile. • Heat sensitive materials are gently treated. • Products and residues are solvent-free. • Fragrances and aromas remain unchanged. • An excellent flavour profile is achieved. • Pure extracts are produced by few process steps. • The solvating power can be changed (conditions, modifiers). • Selective extraction and fractionated separation is possible. • Carbon dioxide is recycled within the plant, is physiologically harmless and does not cause environmental problems like some conventional solvents. Disadvantages: • High capital investment. Solubility of substances in carbon dioxide Easily soluble: Esters, alcohols, aldehydes, ketones, volatile oils, aromas, mono- and sesquiterpenes Reduced solubility: Edible oil from oilseeds, waxes, polyphenols Insoluble: Sugars, fruit acids, starch, proteins, mineral salts, glycosides
Case/substitution evaluation
Supercritical carbon dioxide extraction is often a better technology in regard to product quality, occupational safety and environment. It is a high-cost investment, but more applications are being elaborated giving rise to more companies that can offer the service on contract basis. A product yield devoid of organic solvent residues is also an advantage when it comes to consumer safety.
State of implementation
Full capacity
Availability of Alternative
On the market
Producer/Provider
Type of information supplier
Producer / distributor
Further information
There is a vast amount on scientific literature available on the subject of supercritical CO2 extraction.
Type of publication and availability
Company homepage, freely available
Publication source: author, company, institute, year
Company homepage www.natex.at
Date, reviewed
November 26, 2021