Supercritical fluid’s evolving role in dietary ingredients extraction

September 23, 2020

Supercritical fluid extraction using CO2 is instrumental in replacing conventional solvents.

According to the 2019 Council for Responsible Nutrition Consumer Survey on Dietary Supplements, 77% of adults in the United States take dietary supplements, the highest level of consumption tracked by the survey to date.1 Amidst the significant increase in the consumption of dietary supplements and the awareness of the benefits that dietary supplements provide, consumers are also more aware of product safety concerns. One of the chief concerns of FDA, the agency overseeing supplements in the U.S., regarding potential harmful impurities in dietary supplements that could put consumers at risk centers around residual levels of solvents found in some dietary supplements.2

These residual solvents are introduced through ingredients that have been previously extracted using certain solvents such as ethanol, isohexane, acetone, and ethyl acetate. The residual solvents are defined as organic volatile chemicals that are commonly used in the extraction of dietary ingredients and as a processing aid in the manufacturing of dietary supplements. The residual solvents have no nutritional value and may pose a public health risk. Therefore, there is a need to remove them either from the final products or reduce their amounts to below acceptable levels. Supercritical fluid extraction (SCFE) is a versatile technique which can be employed to extract the concentrate from a biomass without using the conventional solvents, ensuring no residual solvents in the final products while improving product quality.

This article discusses the significance of removal of residual solvents, the need for the SCFE technique, and the process mechanism and benefits as an alternative green technology in removing residual solvents in dietary supplements.

Industry Standard: Removing Residual Solvents

Though there is no regulatory requirement for the removal of residual solvents in dietary supplements or dietary ingredients, there are still good reasons for removing these solvents. For instance, when a dietary supplement is claimed to meet standards such as United States Pharmacopoeia (USP) standards or are registered under the USP Verification Program, then it should meet the criteria for removing the residual solvents.3

In such context, the American Herbal Products Association (AHPA) has adapted the residual solvent guideline provided by The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, ICH Q3C, for dietary supplements.4 This guidance document divides solvents into three risk-based classes: Class 1 solvents, which are known to cause unacceptable toxicities; Class 2 solvents, which are associated with less severe toxicity; and Class 3 solvents, which have low toxic potential. In addition, the guidance also introduces the concept of permitted daily exposure (PDE) and provides the PDE or corresponding concentration limits for Class 1 and Class 2 solvents.

Supercritical Fluid Extraction Technique (SCFE)

Typically, the extraction of dietary ingredients involves the use of organic solvents. The most commonly used solvents in the extraction of dietary ingredients are ethanol, isohexane, acetone, and ethyl acetate. However, there are problems associated with the removal of residual solvents. SCFE is considered to be an alternative green technology which can be employed to replace the conventional solvent extraction technique.

SCFE is the method of separating one component from another component in a mixture using supercritical fluid as the extracting solvent. The commonly utilized solvent is carbon dioxide (CO2) because of its unique characteristic and its nontoxic, nonflammable, and cost-effective properties. Using gas CO2 as a solvent, SCFE can extract the concentrate that is required and separate the soluble active components from a biomass substrate. Because the solvent is CO2 and a gas, the extracted product and the spent biomass are free of residual solvents whereas in the case of extraction using the conventional solvents, there will be residual solvent in both the extracted product and the spent biomass.

The process of SCFE includes pumping the liquid CO2 at a pressure typically above 2000 psi through the heat exchangers and heating up to a temperature ranging from 20 degrees Celsius to 90 degrees Celsius. At this point, CO2 exhibits a unique dissolution property, and this can be replaced with many typical organic solvents. This CO2 is passed through the extractor for a specified period. This time period can vary and is dependent on the type of materials that needs to be extracted.

In the vessel, the extractable component dissolves in the CO2, comes out from the vessel, and is passed through the pressure reducer to the heat exchanger and to the separator. At this point, the CO2 is converted to gaseous CO2, and the extractable material is collected at the bottom of the separator. The vapor CO2 is passed through a condenser and converted into liquid, and then it is reprocessed.

The Cost of Compliance

The cost of an extraction system depends on several factors. For instance, it can be determined by the trade secrets and commercial sensitivity involved in the proprietary solvents developed by industries and commercial organizations. Information to help make the decision about an appropriate system is available either from the literature on non-commercial solvents used by various science and engineering research laboratories or from the industrial guidelines provided by organizations such as AHPA. It is worth noting, however, that most of the industrial system–based information is primarily based on government guidelines such as 29 CFR Part 1926.152(a), 29 CFR 1926.55(a), and so on.

It’s also worth taking other considerations into account when choosing an extraction system. For instance, the solvents used in the extraction of dietary ingredients have an exceptionally low flash point, and as per 29 CFR Part 1926.152(a)(1) “General requirements,” only approved containers and portable tanks shall be used for storage and handling of flammable liquids.5 As per 29 CFR 1926.55(a), employers must limit an employee’s exposure to the commonly used solvents.6 The employer must first implement the administrative or engineering controls whenever feasible. When such controls are not feasible to achieve full compliance, protective equipment or other protective measures shall be used to keep the exposure of employees to air contaminants within the acceptable limits. The byproduct generated during the solvent extraction is saturated with solvent and must be properly handled and disposed of to be in compliance with the U.S. Environmental Protection Agency’s Resource Conservation Recovery Act regulations—whereas in the case of SCFE, the employer doesn’t have to deal with these regulations.


The supercritical fluid extraction technique is a green technology which has the potential to resolve the problem of removing residual solvents. By taking the above constraints into consideration, it is apparent that the solvent extraction technique you choose is strongly dependent on employees’ safety and could be an expensive process.

Extraction technology can improve the quality of the dietary supplements. In conclusion, supercritical fluid extraction using CO2 as a solvent in the extraction of dietary ingredients will not add any residual organic solvents but also removes pesticides and heavy metals from final products. It also will meet the residual-solvents requirements of certification bodies such as the USP.

Karthik Maniam is a director of quality and environmental health safety at Phasex Corp. (North Andover, MA). Maniam is a licensed professional environmental engineer in New York, Vermont, and Massachusetts and holds a master’s degree in environmental technology from New York Institute of Technology and a master’s degree in chemical engineering.


  1. Council for Responsible Nutrition website. 2019 CRN Consumer Survey on Dietary Supplements.
  2. Food and Drug Administration guidance. “Acceptance Criteria for Residual Solvents.” Published June 1997.
  3. The United States Pharmacopeial Convention. General Chapter <467> Residual Solvents. Revised December 1, 2020.
  4. American Herbal Products Association guidance policy. Residual Solvents in Extracts. Retrieved from:
  5. Occupational Safety and Health Administration standard. 1926.152 Flammable liquids. Retrieved from: ​
  6. Occupational Safety and Health Administration standard. 1926.55 Gases, vapors, fumes, dusts, and mists. Retrieved from: