Less Known Facts About Excipients: Squalene

This article is part of the “Less Known Facts About Excipients” series by Philippe Tschopp.

Squalene: A versatile lipid excipient for vaccines and drug delivery

Squalene is one of the few pharmaceutical excipients that has undergone a remarkable transformation in sourcing. Once obtained primarily from deep-sea shark liver oil, pharmaceutical-grade squalene is increasingly sourced from sustainable plant-based feedstocks and biotechnological fermentation.

Although often associated with cosmetics, squalene plays an important role in modern pharmaceuticals, particularly as a component of vaccine adjuvants and advanced drug delivery systems.

Squalene is a naturally occurring triterpene hydrocarbon (C₃₀H₅₀) that is synthesized by virtually all higher organisms. It is a key intermediate in the biosynthesis of cholesterol in humans and phytosterols in plants.¹–³

How is pharmaceutical squalene produced?

Today, pharmaceutical squalene is obtained through three principal routes.

1. Plant Extraction

Squalene is extracted from vegetable oils, particularly:

Olive oil
Amaranth seed oil
Rice bran oil

Following extraction, the material is purified through distillation and other downstream purification processes to achieve pharmaceutical quality. Amaranth-derived squalene has become particularly important because of its naturally high squalene content. [evonik.com ]

2. Fermentation

Modern biotechnology enables microorganisms, including genetically optimized yeast strains, to produce highly pure squalene through controlled fermentation processes.

In some commercial production routes, renewable sugar-based feedstocks serve as the carbon source for microbial squalene production. After fermentation, the squalene is isolated, purified and refined to pharmaceutical specifications.

3. Shark Liver Oil (Historical Source)

For decades, deep-sea shark liver oil was the principal commercial source because certain shark species accumulate exceptionally high concentrations of squalene in their livers.

Today, this source is increasingly being replaced by plant-based and fermentation-derived alternatives due to environmental, sustainability and conservation concerns.

What makes squalene unique?

Squalene is a highly unsaturated linear hydrocarbon containing six double bonds and exhibits exceptional biocompatibility.

Its most valuable pharmaceutical characteristics include:

Excellent biocompatibility
High affinity for lipid-based systems
Lipophilic character
Good compatibility with emulsion formulations
Biodegradability
Endogenous role in human sterol metabolism

Because squalene is a natural intermediate in cholesterol biosynthesis, it is generally well tolerated when used appropriately in pharmaceutical formulations.

Due to its highly unsaturated structure, however, careful purification, storage and formulation strategies are required to minimize oxidative degradation and ensure product stability.

Pharmaceutical applications

Pharmaceutical-grade squalene is used in:

Vaccine adjuvants
Oil-in-water emulsions
Lipid-based drug delivery systems
Injectable formulations
Nanoparticle formulations
Selected topical products¹,²

Its primary functions include:

Oil phase component
Vaccine adjuvant excipient
Lipid carrier
Emulsion component
Drug delivery vehicle

Perhaps its best-known pharmaceutical application is in oil-in-water vaccine adjuvants, where it helps enhance the immune response without acting as the antigen itself.

Considerations for formulators

Source selection has become increasingly important. Plant-derived and fermentation-derived squalene now dominate pharmaceutical development because they provide consistent quality, improved sustainability and reduced dependence on marine resources.

Another important distinction is between squalene and squalane. Squalane is the hydrogenated, fully saturated derivative of squalene and exhibits significantly greater oxidative stability.

While squalane is widely used in topical pharmaceutical and cosmetic formulations, squalene remains the preferred material for certain injectable emulsion systems, including vaccine adjuvants.¹–⁴

Major pharmaceutical manufacturers

Examples of established manufacturers and suppliers include:

Croda Pharma
Evonik Health Care (PhytoSquene®)
Kishimoto Special Liver Oil Co., Ltd.

Did you know?

Although humans naturally produce squalene in the liver and skin, olive oil is among the richest edible plant sources of squalene, with concentrations that can vary significantly depending on variety and processing conditions.

Historically, pharmaceutical production relied heavily on deep-sea shark liver oil because certain shark species can contain exceptionally high concentrations of liver oil, a substantial fraction of which may be squalene.

Today, advances in biotechnology allow manufacturers to produce the exact same molecule through precision fermentation, helping to reduce pressure on marine ecosystems while maintaining pharmaceutical quality and supply security. [evonik.com ], [crodapharma.com ]

By Philippe Tschopp
Philippe Tschopp writes about pharmaceutical excipients, formulation and oral drug delivery, with a focus on excipient functionality, practical formulation considerations and lesser-known material properties.

Source:

Rowe RC, Sheskey PJ, Quinn ME (Eds.). Handbook of Pharmaceutical Excipients. Pharmaceutical Press / American Pharmacists Association.
European Pharmacopoeia (Ph. Eur.). Relevant monographs and general chapters covering pharmaceutical excipients and lipid components.
Giner JL. Squalene and Sterol Biosynthesis. Chemical Reviews.
Croda Pharma. Technical documentation for pharmaceutical lipid excipients and vaccine formulation components. [crodapharma.com ]
WHO. Vaccine Adjuvants: Preparation Methods and Characterization.
Popa O, et al. Methods for Obtaining and Characterization of Squalene from Natural Sources. BioMed Research International.
Evonik Health Care. PhytoSquene® Plant-Based Pharmaceutical-Grade Squalene.

Disclaimer

This article is based on publicly available information and industry sources at the time of writing and supported by AI. While every effort has been made to ensure accuracy, completeness, and fair representation, the author does not guarantee that all information is current, error-free, or reflective of the latest developments.

The content is provided for informational and educational purposes only and does not constitute technical, regulatory, or commercial advice. No liability is accepted for decisions made based on this material. Readers are encouraged to consult the original manufacturers and official sources to verify details before making professional or business decisions.