Discovery makes 'green' separation open to pharma

Related tags Carbon dioxide Pharmacology

One of the most chemically benign separation processes could for
the first time be made available to manufacturers in the
pharmaceutical industry, thanks to pioneering work carried out by
researchers in the US.

The team, from Virginia Polytechnic Institute and State University (Virginia Tech) , have found a way that could allow a green-chemistry technique known as supercritical fluid chromatography (SFC) to be used in for drug compounds.

Drugs must be water-soluble in order to be useful in the body, meaning they are polar, or have some degree of charge. SFC uses carbon dioxide-based fluids for the isolation of compounds. But because carbon dioxide is not polar, the technique could not be used to separate most drug compounds.

The Virginia Tech researchers, led by chemistry professor Larry Taylor, found that by adding a small amount of polar solvent into the SFC process, carbon dioxide could be used to separate polar compounds, which they refer to as ionic analytes.

"It opens up an area of drug development to the use of non-polluting carbon dioxide,"​ said Taylor. Using other forms of chromatography requires the use of flammable and toxic hydrocarbon-based solvents. And while CO2 is a greenhouse gas and carries its own environmental concerns

As a technique, SFC was lauded as the future of chromatography in the 1980s, but almost disappeared in the 1990s as scientist were frustrated by the lack of well-designed instruments and high performance liquid chromatography (HPLC) took off as an analytical tool.

Despite this, SFC has continued to be exploited, because of its potential for lower solvent procurement costs, faster chromatography, a longer lasting stationary phase, lower energy costs and low disposal costs.

Pharmaceutical companies have been reluctant to adopt SFC, despite advances in instrumentation from the likes of Thar Technologies, Novasep and Mettler-Toledo, because HPLC is perceived as the more versatile tool and companies want to be able to carry out as much work as possible with each instrument they buy.

On a lab scale drug companies have tended to use HPLC, moving up to multicolumn technologies such as simulated moving bed chromatography for industrial-scale applications. Advances such as the work at Virginia Tech could hasten uptake of SFC across these applications, particularly for separation of chiral drugs, as it promises to reduce solvent use and waste, at least for applications up to kilo-scale production, and so could cut costs.

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