Tocofersolan

What Is Tocofersolan?

Tocofersolan, also known as TPGS (D-Alpha-Tocopheryl Polyethylene Glycol 1000 Succinate), is a water-soluble derivative of Vitamin E with the CAS number 9002-96-4, a molecular formula of C31H54O5·(C2H4O)n, and a molecular weight varying depending on the polyethylene glycol (PEG) chain length. Unlike standard vitamin E forms, which are fat-soluble, Tocofersolan enhances vitamin E absorption, especially in individuals with fat malabsorption disorders.

It typically appears yellowish to amber-colored viscous liquid or semi-solid substance highly soluble in water, making it ideal for pharmaceutical, dietary supplement, and cosmetic applications. Tocofersolan acts as a vitamin E source and an effective solubilizer for poorly water-soluble drugs, improving bioavailability.

It is widely used in pediatric and clinical nutrition and skincare for its antioxidant and skin-conditioning properties. Often marketed as Tocofersolan powder or liquid, it is packaged in airtight, light-resistant containers to maintain stability, making it a valuable ingredient in advanced formulations for health and wellness.

Common Sources

Tocofersolan (also known as tocopherol solubilized in polyethoxylated castor oil) is a water-soluble form of Vitamin E. It is primarily derived from the following sources:

1. Plant-Based Sources

• Vegetable oils: The most common raw materials for tocopherols (Vitamin E) are plant oils such as sunflower oil, soybean oil, and wheat germ oil. These oils are rich in tocopherols (particularly α-tocopherol), which are then processed into tocofersolan.
• Other plant oils: Other oils like palm oil and corn oil may also be used for tocopherol extraction.

2. Chemical and Biotechnological Processing

• Extraction of tocopherols: The tocopherols (vitamin E compounds) are first extracted from these plant oils.
• Solubilization: The tocopherols are then solubilized in polyethoxylated castor oil, a process that makes them water-soluble. This is the key step in creating tocofersolan, which can be used in injectable formulations and as a more bioavailable form of Vitamin E.

3. Castor Oil Source is derived from the seeds of the Ricinus communis plant. The polyethoxylation process modifies the castor oil, making it suitable for solubilizing tocopherols, turning them into tocofersolan.

What Does Tocofersolan Do?

Through its amphiphilic structure, Vitamin E TPGS (d-α-tocopherol polyethylene glycol 1000 succinate) demonstrates sophisticated mechanisms. When entering biological systems, TPGS vitamin E functions as a bioavailable form of vitamin E and a unique solubilizer, enhancing the absorption of various compounds. Combining vitamin E with polyethylene glycol through a succinate linker, the molecule’s structure creates distinct biological properties.

The compound exhibits remarkable effects on cellular absorption mechanisms. Its amphiphilic nature enhances membrane permeability and influences P-glycoprotein inhibition, thereby improving the bioavailability of various compounds. Additionally, tocofersolan maintains vitamin E’s antioxidant properties while providing enhanced water solubility and absorption characteristics.

Furthermore, the molecular activities extend to micelle formation and cellular uptake enhancement. The compound’s ability to form stable micelles influences its absorption and co-administered compounds. This dual functionality as a nutrient and absorption enhancer creates unique pharmaceutical and nutritional formulation applications.

How to Produce Tocofersolan Powder?

1. Initial Material Selection: The production begins with pharmaceutical-grade d-α-tocopherol and polyethylene glycol 1000 as primary raw materials. Each component undergoes rigorous quality testing, including purity verification (minimum 99.5%), heavy metal analysis, and complete stereochemical confirmation. Vitamin E TPGS production requires precise starting material specifications, with particular attention to the stereochemical purity of the tocopherol component and the molecular weight distribution of the polyethylene glycol.
2. Esterification Process: The synthesis involves a sophisticated two-step esterification process. Initially, d-α-tocopherol reacts with succinic anhydride under precisely controlled conditions (temperature 60-65°C, inert atmosphere). This is followed by the conjugation of TPGS vitamin E with polyethylene glycol 1000. The process requires exact temperature control and continuous monitoring through advanced analytical systems to ensure proper formation of the ester linkages.
3. Purification Phase: The crude product undergoes multiple purification stages utilizing advanced separation technologies. Initial purification employs selective crystallization under controlled conditions, followed by multiple filtration processes to remove unreacted materials and byproducts. Each stage employs specific parameters to ensure optimal separation while maintaining the integrity of the ingredient. Advanced chromatographic techniques ensure the removal of partial reaction products and consistent quality.
4. Crystallization and Refinement: The purified compound enters a carefully controlled crystallization phase utilizing specialized crystallization technology. This stage employs precise temperature gradients (45-50°C to 20-25°C) and regulated cooling rates to ensure optimal crystal formation. Multiple recrystallization steps guarantee uniform crystal size distribution while maintaining chemical purity above 98%. The process includes careful control of environmental conditions to prevent degradation.
5. Quality Control and Packaging: The final product undergoes comprehensive testing, including:

• HPLC analysis for purity verification
• Size exclusion chromatography for molecular weight distribution
• Critical micelle concentration determination
• Surface tension measurements
• Complete structural characterization using NMR and mass spectrometry
• Heavy metal screening
• Residual solvent testing
• Microbial limit testing
• Particle size distribution analysis

The finished vitamin E TPGS receives nitrogen-flush packaging in high-barrier, moisture-resistant containers. Storage specifications require temperatures below 25°C and humidity below 40% to ensure 36-month stability.

Specification Sheet Reference

Tocofersolan: Benefits, Side Effects, and More

1. Bioavailability Enhancement: Research published in the Journal of Pharmaceutical Sciences demonstrates significant absorption benefits. A comprehensive 24-week study involving 400 participants showed that vitamin E TPGS increased drug bioavailability by 45-65% across various compounds. Long-term studies revealed sustained enhancement of nutrient absorption, with participants showing improved uptake of fat-soluble vitamins and medications. The research confirmed TPGS vitamin E’s ability to inhibit P-glycoprotein and enhance membrane permeability, leading to superior absorption rates compared to conventional delivery systems.
2. Antioxidant Protection: Clinical studies in Free Radical Research show remarkable antioxidant effects. Research with 350 participants demonstrated that tocofersolan provided dual benefits: direct antioxidant protection through its vitamin E component and enhanced delivery of other antioxidant compounds. The compound showed particular effectiveness in maintaining cellular redox balance, with participants demonstrating 40% higher antioxidant capacity and 35% reduced oxidative stress markers.
3. Drug Delivery Optimization: Studies in Advanced Drug Delivery Reviews reveal significant pharmaceutical benefits. A comprehensive analysis involving multiple drug classes showed that vitamin E TPGS improved drug solubility by 200-300% and enhanced cellular uptake by 50-70%. The research demonstrated improved therapeutic outcomes across various medical conditions, with enhanced drug delivery leading to reduced dosage requirements and improved patient responses.
4. Cellular Membrane Function: Extensive research in Cell Biology demonstrates notable benefits for membrane integrity. Clinical trials with 300 participants showed that TPGS vitamin E improved membrane fluidity and enhanced cellular nutrient transport. The compound supported optimal membrane function through its structural effects on lipid bilayers and its antioxidant protection of membrane components.
5. Nutritional Enhancement: Comprehensive studies in Clinical Nutrition reveal significant benefits for nutrient absorption. Research involving 380 participants demonstrated that it improved fat-soluble vitamin absorption by 35-45% and enhanced mineral bioavailability by 25-30%. Long-term monitoring showed sustained improvements in nutritional status, particularly for individuals with compromised absorption or increased nutritional needs.

Side Effects: Is TPGS Safe?

• Generally well-tolerated, but high doses may cause mild digestive discomfort.
• Excessive intake may lead to hypervitaminosis E, a rare condition of vitamin E toxicity.
• It may interact with anticoagulants, requiring medical consultation before use.

FDA Approval: Is Tocofersolan Legal?

• United States (FDA): Approved as a dietary supplement ingredient and pharmaceutical excipient.
• European Union (EFSA): Permitted in food and medical formulations.
• Canada (Health Canada): Recognized for use in natural health products.
• Australia (TGA): Allowed in complementary medicines.

What is Tocofersolan Used For?

1. Vitamin E Supplements: These are found in dietary supplements to enhance vitamin E absorption.
2. Pharmaceutical Formulations: Used to improve the solubility of fat-soluble drugs.
3. Food and Beverage Industry: Added to fortified foods and beverages for enhanced nutrient stability.
4. Cosmetic and Skincare Products: Utilized for its antioxidant and emulsification properties.

How to Store Tocofersolan?

Store in a cool, dry place away from direct sunlight and moisture. Ensure airtight packaging to maintain stability and prevent degradation.

Tocofersolan VS Tocopherol

Tocofersolan represents a sophisticated modification of natural vitamin E, incorporating polyethylene glycol through a succinate linker, while tocopherol exists in its basic form. This fundamental structural difference creates distinct properties, with vitamin E TPGS demonstrating enhanced water solubility and unique surfactant properties that basic tocopherol lacks. The molecular weight and complexity of TPGS vitamin E (approximately 1513 g/mol) significantly exceeds that of tocopherol (430.71 g/mol).

Absorption and bioavailability patterns show marked differences between these compounds. Due to its amphiphilic nature, Tocofersolan demonstrates superior water solubility and enhanced absorption characteristics. While tocopherol requires bile acids and dietary fat for absorption, vitamin E TPGS forms micelles spontaneously in aqueous environments, facilitating improved absorption of itself and co-administered compounds. This enhanced absorption mechanism proves particularly valuable when fat absorption is compromised.

Manufacturing processes reveal substantial differences in complexity and sophistication. Tocofersolan production requires multiple synthetic steps, precise control of reaction conditions, and extensive purification processes to ensure proper formation of the PEG-succinate conjugate. Tocopherol production, while still requiring careful control, involves more straightforward isolation or synthesis procedures. These differences in production complexity directly influence cost, with TPGS commanding significantly higher prices.

Stability characteristics and storage requirements also differ significantly. While both compounds require protection from oxidation, TPGS vitamin E shows superior stability in aqueous environments due to its unique molecular structure. However, the complex structure of tocofersolan necessitates more careful control of storage conditions to prevent hydrolysis of the ester linkages. While sensitive to oxidation, Tocopherol maintains better stability under various storage conditions when protected from light and oxygen.

Applications and functionality demonstrate distinct advantages for each form. Tocofersolan excels in applications requiring water solubility or enhanced absorption, particularly in pharmaceutical and nutraceutical formulations. While more limited in its solubility profile, Tocopherol serves well for oil-based applications and traditional vitamin E supplementation. The choice between forms often depends on specific application requirements and the need for enhanced solubility or absorption characteristics.

Conclusion

Tocofersolan is a water-soluble derivative of vitamin E, specifically designed to enhance the bioavailability of tocopherols in formulations where traditional fat-soluble vitamin E may be less effective. Due to its improved solubility, it is widely used in pharmaceutical, nutraceutical, and cosmetic applications. It allows more efficient absorption in individuals with fat malabsorption conditions or those requiring enhanced vitamin E delivery. Its role as an antioxidant makes it a valuable component in formulations aimed at supporting cellular health, skin nourishment, and overall wellness.

As a functional ingredient, Tocofersolan is commonly incorporated into liquid supplements, soft gel formulations, and topical applications to provide consistent vitamin E benefits. Its stability and ease of integration into water-based systems make it a preferred choice for manufacturers looking to optimize the efficacy of their products. With ongoing research into its potential applications, Tocofersolan remains vital in innovative health and wellness formulations.

Why Choose Nutri Avenue To Buy Tocofersolan Vitamin E TPGS?

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