ALEXANDER KLAIBER, UWE ALBRECHT, MARKUS JUZA*
*Corresponding author
CordenPharma Switzerland LLC, Liestal, Switzerland

Abstract

Synthetic lipids have recently been used with great success in mRNA lipid nanoparticles (LNP) formulations, which has greatly increased their demand. Chromatography still remains a standard unit operation in the purification of these lipids. However, traditional normal phase chromatography often uses large amounts of toxic solvents, including chlorinated ones. In this article we present three case studies demonstrating alternative methods to achieve greater sustainability and/or reduce both environmental impact and operational cost. These methods include aqueous/non-aqueous reversed-phase chromatography (NARP) as well as super critical fluid chromatography (SFC).

INTRODUCTION
Lipid Nanoparticles (LNPs) became widely known in the COVID-19 pandemic by playing a major role in the development of SARS-CoV-2 vaccines (1).
Nowadays, LNPs are one of the most commonly used tools for xRNA (2, 3) and xDNA delivery (4). LNPs usually consist of five components, ionizable lipids, phospholipids, cholesterols, pegylated lipids, and the payload, each of them adding unique properties to the structure of the LNP. Therefore, synthetic lipids as well as lipid conjugates have been gaining significant importance in recent years as drug target, therapeutic molecules, and liposomes.

Traditionally such molecules are purified by normal phase chromatography on silica using large volume of toxic solvents, including chlorinated solvents. As CDMO and producer of numerous lipids CordenPharma accepted the challenge of reducing organic solvent usage and developing greener processes. Ways to achieve this goal include aqueous/non-aqueous reversed-phase chromatography (NARP) (5, 6) and super critical fluid chromatography (SFC) that can be considered to supplant organic solvents (7) with more benign alternatives. In SFC ...