Tocofersolan (Vitamin E TPGS) CAS 9002-96-4 / Articles

Tocofersolan (Vitamin E TPGS): Structure, Properties, and Applications

1. Introduction

Tocofersolan (commonly known as Vitamin E TPGS, D-α-tocopheryl polyethylene glycol 1000 succinate) is a water‑soluble derivative of natural vitamin E (α‑tocopherol). It was developed in 1950 by Eastman Kodak as a hydrophilic form of vitamin E to treat deficiency in patients with fat malabsorption. TPGS combines the antioxidant properties of vitamin E with the amphiphilic character of polyethylene glycol, making it a versatile multifunctional excipient in pharmaceutical, cosmetic, and food industries.

2. Chemical Structure and Nomenclature

Chemical name: D-α-Tocopheryl polyethylene glycol 1000 succinate

INCI name: Tocophersolan

Synonyms: Vitamin E TPGS, TPGS-1000, TPGS, Tocofersolan

CAS number: 9002-96-4

UNII: O03S90U1F2

Molecular formula: (C₂H₄O)ₙC₃₃H₅₄O₅

Molecular weight: ~1513 g/mol (PEG 1000 conjugate)

Structure: TPGS consists of a lipophilic vitamin E (α‑tocopherol) tail linked via a succinate ester to a hydrophilic PEG‑1000 chain. This amphiphilic structure enables self‑assembly into micelles and interaction with both aqueous and lipid phases.

3. Physicochemical Properties

Appearance: White to light tan waxy solid

Melting point: 37–41°C

Density: 1.06 g/cm³ at 45°C

Solubility: Soluble in water; forms micellar solutions; soluble in alcohols and organic solvents

HLB (Hydrophilic‑Lipophilic Balance): ~13.2 – high, indicating a hydrophilic (O/W) surfactant

CMC (Critical Micelle Concentration): ~0.02% w/w (~0.02 mM) – low, allowing micelle formation at low concentrations

4. Mechanism of Action

TPGS acts through several complementary mechanisms:

Solubilization: Forms micelles that encapsulate poorly soluble drugs, vitamins, and lipophilic compounds, increasing their apparent solubility.
Emulsification: As a non‑ionic surfactant with high HLB, it stabilizes oil‑in‑water emulsions and nanoemulsions.
Permeation enhancement: Increases drug permeability across biological membranes, including intestinal epithelium and skin.
P‑glycoprotein (P‑gp) inhibition: Inhibits the efflux transporter P‑gp, reducing drug elimination from cells and improving intracellular drug retention.
Antioxidant activity: The vitamin E moiety provides free‑radical scavenging activity, protecting formulations and biological tissues from oxidative damage.

5. Applications

Pharmaceuticals:

Solubility and bioavailability enhancement: TPGS is widely used as an excipient in solid dispersions, nanocrystals, micelles, liposomes, and nanoemulsions to improve the oral bioavailability of poorly soluble drugs (e.g., anticancer agents, antivirals, immunosuppressants).
Drug delivery systems: Used in parenteral, oral, topical, transdermal, and ocular formulations.
Pediatric vitamin E supplementation: Approved as an oral therapy for vitamin E deficiency in children with cholestatic liver disease.

Cosmetics and personal care:

Functions as an emulsifier, solubilizer, stabilizer, and antioxidant in creams, lotions, serums, and sunscreens.
Enhances skin penetration of active ingredients.

Nutraceuticals and functional foods:

Used as a water‑soluble source of vitamin E in dietary supplements, beverages, and functional food products.

6. Regulatory Status and Safety

TPGS is recognized as safe by multiple regulatory authorities:

FDA: Approved as an inactive pharmaceutical ingredient (Tocophersolan, UNII O03S90U1F2). Self‑affirmed GRAS (Generally Recognized As Safe) for food use.
Cosmetics: Rated as "EXCELLENT" for safety by the Cosmetic Ingredient Review (CIR) and permitted in cosmetics in the US, EU, and China.
UK and Canada: Included in the Canadian List of Acceptable Non‑medicinal Ingredients and UK non‑parenteral medicines guides.

With over 70 years of safe use, TPGS has a well‑established safety profile at recommended concentrations.

7. Conclusion

Tocofersolan (Vitamin E TPGS, CAS 9002‑96‑4) is a versatile, water‑soluble derivative of natural vitamin E that combines antioxidant activity with surfactant, emulsifying, and solubilizing properties. Its ability to enhance the solubility, permeability, and bioavailability of poorly soluble compounds, along with its P‑gp inhibition and antioxidant effects, makes it an invaluable excipient in drug delivery, cosmetics, and functional foods. Its favorable safety profile and regulatory acceptance across multiple jurisdictions support its continued and expanding use in pharmaceutical and nutraceutical formulations.