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Review Article
Pharmaceutical Profile of Alpha-Tocopherol – A Brief
Waghmode Maya*, Kamble Mayur and Shruti Ashar

Kashibai Navale college of Pharmacy, Kondhwa, Pune, Maharashtra, India.

Vitamins are organic compounds which are not synthesized in body, so should be supplied from the
diet and sunlight (Vitamin D). The vitamins are broadly classified as Fat soluble and Water soluble
vitamin. Vitamin E is Fat soluble vitamin known as anti sterility factor or alpha Tocopherol or fat
soluble vitamin. Chemically Vitamin E is 2-methyl-20(4’, 8’, and 12 -trimethyletridecyle)–chromane
6-ol.Vitamin E can be useful therapeutically and also used as pharmaceutical aid. The therapeutic
dose of vitamin E can be given by Dietary References Intakes (DRI) developed by FNB. The
recommended dietary allowance of Vitamin E can be expressed in International Unit. The present
study includes illustration of chemistry of vitamin E, properties; pharmacology; Interactions of
vitamin E. Commercially forms of vitamin E, their use in various formulations are discussed.
Analytical profile and Evaluation study of one formulation containing tocopherol, Marketed product
is discussed.

Keywords: Vitamin E, Alpha Tocopherol, TPGS, Antioxidant, Gas chromatography.

VITAMIN micronutrient class, and the word was

A vitamin is an organic compound required as shortened to vitamin..
a nutrient in tiny amounts by an organism. In Vitamins are classified by their biological and
other words, an organic chemical compound chemical activity, not their structure. Thus,
(or related set of compounds) is called a each "vitamin" refers to a number of vitamer
vitamin when it cannot be synthesized in compounds that all show the biological
sufficient quantities by an organism, and must activity associated with a particular vitamin.
be obtained from the diet. Thus, the term is Such a set of chemicals are grouped under
conditional both on the circumstances and the an alphabetized vitamin "generic descriptor"
particular organism. For example, ascorbic title, such as "vitamin A", which includes the
acid (vitamin C) is a vitamin for humans, but compounds retinal, retinol, and four known
not for most other animals, and biotin and carotenoids. Vitamers by definition are
vitamin D are required in the human diet only convertible to the active form of the vitamin in
in certain circumstances. By convention, the the body, and are sometimes inter-convertible
term vitamin does not include other essential to one another, as well. Vitamins have diverse
nutrients such as dietary minerals, essential biochemical functions. Some have hormone-
fatty acids or essential amino acids (which are like functions as regulators of mineral
needed in larger amounts than vitamins), nor metabolism (e.g. vitamin D), or regulators of
does it encompass the large number of other cell and tissue growth and differentiation (e.g.
nutrients that promote health, but are some forms of vitamin A). Others function as
otherwise required less often. Thirteen antioxidants (e.g. vitamin E and sometimes
vitamins are presently universally recognized. vitamin C).The largest number of vitamins
The term vitamin was historically derived from (e.g. B complex vitamins) function as
"vitamine," a combination word made up by precursors for enzyme cofactors, which help
Polish scientist Casimir Funk from vital and enzymes in their work as catalysts in
amine, meaning amine of life. Because it was metabolism. In this role, vitamins may be
suggested in 1912 that the organic tightly bound to enzymes as part of prosthetic
micronutrient food factors which prevented groups: for example, biotin is part of enzymes
beriberi and perhaps other similar dietary- involved in making fatty acids. Alternately,
deficiency diseases, might be due to chemical vitamins may also be less tightly bound to
amines. This proved incorrect for the enzyme catalysts as coenzymes, detachable
molecules which function to carry chemical

Vol. 1 (3) Jul-Sep 2012 1023


groups or electrons between molecules. For enzyme-substrate reactions are vitamin’s

example, folic acid carries various forms of best-known function, the other vitamin
carbon group – methyl, formyl and methylene functions are equally important.
– in the cell. Although these roles in assisting

rats was named Vitamin E. When the

Names of Vitamins compound known as
Fat soluble vitamins Vitamin E and was isolated in 1936 which
Vitamin A- Retinol; Vitamin D- Ergocalciferol; was named as tocopherol. Since then,
Vitamin E- Tocopherol; Vitamin K- several other closely related compounds have
Menadione. been discovered from natural sources, and
family of natural products took the generic
Water soluble vitamins name Tocopherols.
B-complex Energy Releasing vitamin Tocopherols are especially abundant in wheat
Vitamin B1 – Thiamine; Vitamin B2 – germ rice, germ, corn germ, other seed
Riboflavin; Vitamin B3 – Niacin; Vitamin B5 - germs, lettuce, soya and cottonseed oil. All
Panthothenic Acid; Vitamin B6 – Pyridoxine; green plants contain some tocopherols. All
Vitamin B7-Biotin tocopherols have been found in wheat germ
oil (α-, β-, γ-, δ-tocopherols).α-, β-, γ-
Hematopoietic vitamin tocopherols have been found in cottonseed
Vitamin B12-Cyanocobalamine; Folic acid oil. Corm oil contains predominantly γ-
tocopherol.δ-tocopherol is 30% of the mixed
Non B complex tocopherols of soya bean oil.
Vitamin M; Ascorbic acid
ALPHA TOCOPHEROL or VITAMIN E In general, food sources with the highest
Introduction concentrations of vitamin E are vegetable oils,
Since the early 1920s, it was found that rats followed by nuts and seeds including whole
fed of cow’s milk could not produce offspring. grain. Although originally extracted from
The principle from wheat germ that could wheat germ oil, most natural vitamin E
rectify this deficiency in both male and female supplements are now derived from vegetable
oils, usually soybean oil, walnut oil, peanut oil,
olive oil, maize.

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Table 2: Vitamin E content per 100 g of source

Source of Vitamin Amount /100 gm
Wheat germ oil (215.4 mg)
Sunflower oil (55.8 mg)
Almond oil (39.2 mg)
Sunflower seed (35.17 mg)
Almond 26.2 mg)
Hazelnut (26.0 mg)
Walnut oil (20.0 mg)
Peanut oil (17.2 mg)
Olive oil (12.0 mg)
Poppyseed oil (11.4 mg)
Peanut (9.0 mg)
Pollard (2.4 mg)
Maize (2.0 mg)
Poppy seed (1.8 mg)
Asparagus (1.5 mg)
Oats (1.5 mg)
Chestnut (1.2 mg)

Table 3: Recommended Dietary Allowances (RDAs) for

Vitamin E (Alpha-Tocopherol)
Age Males Females Pregnancy Lactation
0-6 months 4 mg(6 IU) 4 mg(6 IU) ------------- -------------
7-12 months 5 mg(7.5 IU) 5 mg(7.5 IU) ------------- -------------
1-3 years 6 mg(9 IU) 6 mg(9 IU) ------------- -------------
4-8 years 7 mg(10.4 IU) 7 mg(10.4 IU) ------------- -------------
9-13 years 11 mg(16.4 IU) 11 mg(16.4 IU) ------------- -------------
14+ years 15 mg(22.4 IU) 15 mg(22.4 IU) 15 mg(22.4 IU) 19 mg(28.4 IU)

Intake recommendations for vitamin E and tocopherol; the synthetically produced form is
other nutrients are provided in the Dietary dl-alpha-tocopherol.
Reference Intakes (DRIs). DRI are developed Conversion rules are as follows:
by the Food and Nutrition Board (FNB) at the • To convert from mg to IU: 1 mg of alpha-
Institute of Medicine of The National tocopherol is equivalent to 1.49 IU of the
Academies (formerly National Academy of natural form or 2.22 IU of the synthetic form.
Sciences). DRI is the general term for a set of • To convert from IU to mg: 1 IU of alpha-
reference values used to plan and assess tocopherol is equivalent to 0.67 mg of the
nutrient intakes of healthy people. These natural form or 0.45 mg of the synthetic form.
values vary by age and gender which include: Table 3 lists the RDAs for alpha-tocopherol in
• Recommended Dietary Allowance (RDA): both mg and IU of the natural form; for
average daily level of intake sufficient to meet example, 15 mg x 1.49 IU/mg
the nutrient requirements of nearly all (97%-
• Adequate Intake (AI): established when Synonym
evidence is insufficient to develop an RDA Antisterility factor, alpha Tocopherol, fat
and is set at a level assumed to ensure soluble vitamin.
nutritional adequacy. Vitamin E is a generic term used for a group
• Tolerable Upper Intake Level (UL): of chemically-similar compounds sharing the
maximum daily intake unlikely to cause tocopherol and tocotrienol structures, which
adverse health effects. are lipid-soluble; hence, vitamin E is known
At present, the vitamin E content of foods as a fat-soluble vitamin. Vitamin E is an
and dietary supplements is listed on labels in important anti-oxidant which protects against
international units (IUs); IU is a measure of lipid peroxidation (which could contribute to
biological activity rather than quantity. cell membrane weakness).
Naturally sourced vitamin E is called d-alpha-

Vol. 1 (3) Jul-Sep 2012 1025



Molecular formula Acid Value –NMT-2 determined on 2.09.

Free tocopherol-NMT 2 % Sulphated Ash-
Molecular weight .1%
Tocopherol acetate is -2RS, 4’RS, 8’RS)-6- CHEMISTRY OF VITAMIN E
acetoxy-2, 5, 7, 8 (tetramethyl)-2-(4’, 8’, 12’- The vitamin activity was first identified in
trimethyltridecyle) Chromane. 1936 from a dietary fertility factor in rats, it
was given the name "tocopherol" from the
Category Greek words i.e. birth and bear or carry
Vitamin E supplement, Antioxidant. meaning in sum "to carry a pregnancy," with
Dose the ending "-ol". Vitamin is collective term for
Prophylactic 5-10mg, Therapeutic dose to be Fat soluble 6-hydroxychroman compounds
determined by the physician according to that exhibit the biological activity.Tocol is (2-
needs of patients. methyl-2-(4’, 8’and 12’-trimethyltridecyle)-
chroman-6-ol) is generally considered as the
Description parent compound of the tocopherols.
Clear slightly greenish yellow, viscous oily Naturally occurring vitamin E consists of α-, β-
Liquid. , γ- and δ-tocopherol and corresponding α-, β-
, γ- and δ-tocotrienol. The tocopherols are
Solubility characterized by the 6-chromanol ring
Freely soluble in Acetone, in Chloroform, in structure methylated to varying degrees at the
Ethanol (95%), in Ether, and in Fixed oil, 5, 7, and 8 positions. At position 2, there is a
practically insoluble in Water. C16 saturated side chain. The tocotrienols
are unsaturated at the 3’, 7’and 11 positions
Standard of side chain. The specific tocopherols and
Tocopheryl acetate contains NLT 96.0% And tocotrienols differ by number and positions of
NMT 102.0% of C31H52O3. methyl groups on 6-chromanol ring. α-
Tocopherol and α-Tocotrienols are
Storage trimethylated, β-Tocopherol, β-Tocotrienols
Store in well closed, light resistant containers. and γ -Tocopherol, γ-Tocotrienols are
Refractive Index-Between 1.49-1.498 at 200 dimethylated while δ-Tocopherol and δ—
Tocotrienols are monomethylated.

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Structure of Alpha tocopherol

Structure of Alpha tocotrienol

Structures of tocopherols and tocotrienols

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Structure Activity Relationship of Alpha position 2.consequently, only,2R and 2S

Tocopherol stereoisomers are possible 3’,7’ of phytyl side
Vitamin E exists in eight different forms, four chain permits four cis/trans geometric
tocopherols and four tocotrienols. All feature a isomers. But in nature only 2R, 3’- Tran’s,
chromanol ring, with a hydroxyl group that 7’-Tran’s isomer exits in nature.
can donate a hydrogen atom to reduce free Isolation and elucidation of the structural
and a hydrophobicside chain which allows for properties of vitamin E were accomplished in
penetration into biological membranes. the 1960 by Pennock and Ternes, Isler and
Both the tocopherols and tocotrienols occur in associates research groups.
alpha, beta, gamma and delta forms,
determined by the number and position of Physiological Aspects of Vitamin E
methyl groups on the chromanol ring. Absorption
The tocotrienols have the same methyl The process of absorption is passive and
structure at the ring and the same Greek does not require the use of a protein carrier to
letter-methyl-notation, but differ from the bring vitamin in blood. Absorption occurs in
analogous tocopherols by the presence of the small intestine and the vitamin can only
three double bonds in the hydrophobic side be absorbed if it has been cleaved by
chain. The unsaturation of the tails gives esterase enzyme located in the stomach
tocotrienols only a single stereoisomeric lining. It is then packaged into very low-
carbon (and thus two possible isomers per density lipoproteins (VLDL) by the addition of
structural formula, one of which occurs lipid-like substances. VLDLs enter the
naturally), whereas tocopherols have 3 lymphatics and are eventually released into
centers (and eight possible stereoisomers per the bloodstream. The alpha-tocotrienol
structural formula, again, only one of which appears to be better absorbed than the other
occurs naturally). tocopherol forms.
Each form has slightly different biological
activity. In general, the unnatural l-isomers of Transport
tocotrienols lack almost all vitamin activity, Vitamin E does not have a specific carrier
and half of the possible 8 isomers of the protein in the bloodstream but it is transferred
tocopherols (those with 2S chirality at the by hepatic and lymphatic mechanisms. When
ring-tail junction) also lack vitamin activity. Of it is first absorbed into the hepatic portal vein
the stereoisomers which retain activity, which contains a lipid like structure called a
increasing methylation, especially full chylomicron. This structure is then converted
methylation to the alpha-form, increases hepatically to three distinct lipoprotein
vitamin activity. In tocopherols, this is due to structures:
the preference of the tocopherol binding 1) High-density lipoprotein (HDL) 2) Low-
protein for the alpha-tocopherol form of the density lipoprotein (LDL) 3) Very Low Density
vitamin. lipoproteins (VLDL).
As a food additive, tocopherol is labeled with The alpha-tocotrienol is the form most rapidly
these E numbers: E307 (α-tocopherol), E308 secreted into the plasma after uptake.
(γ-tocopherol), and E309 (δ-tocopherol. The transport process is an important aspect
in the delivery of vitamin E. Without the
Stereochemistry of Vitamin E protective barrier of the lipoproteins (HDL,
The Tocopherols possess three asymmetric LDL, and VLDL), the vitamin would be
carbons (chiral centers) at position 2 of the exposed to the oxidative radicals circulating
chromanol ring and at positions 4’, and 8’ of through the blood. Additionally, vitamin E will
the phytyl side chain. Synthetic α tocopherol prevent the oxidation of LDL; oxidized LDL is
(all-rac-α-T) is a racemic mixture of equal thought to be a factor in atherosclerosis, so
parts of each stereoisomer. Therefore, each adequate amounts of vitamin E will help
tocopherol has eight (23) possible optical protect against hardening of the arteries,
isomers. Only RRR-Tocopherols are found in heart attacks, and stroke.
nature. The eight isomers of all-rac-α-T(RRR-
,RSR-,RRS-,RSS-,SRR-,SSR-,SRS-,and Tissue Uptake
SSS-).From these isomer only 2R containing Tissue uptake occurs by one of two ways 1)
compound is considered as active for human by lipases digesting the lipoprotein
beings. constituents 2) by "receptor mediated uptake"
Tocotrienols arising from 2-methyle -2- by binding of the lipoprotein to a specific
(4’,8’,12’-trimethyltrideca-3’,7’,11’-trienyl) tissue receptor site. This allows for the
chroman-6-ol9 (nonmethylated ring vitamin to enter the tissue.
structure)have only one chiral center at

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Vitamin E enters a variety of different tissue delay the chronic diseases associated with
types, with adipose and the adrenal gland free radicals.
having the highest levels. It is found primarily
in mitochondria. It is thought to play a role 2) Immune Activity
there in either stabilizing ubiquinone, or in In addition to its activities as an antioxidant,
helping ubiquinone transfer electrons. vitamin E is involved in immune function in
The body's capacity for storage of the vitamin cell signaling, regulation of gene expression,
is worth noting. The vitamin can be stored in and other metabolic processes.
tissue for long periods of time (years) due to
its exceedingly slow turnover rate. 3) Anticancer activity
Interestingly, the natural R, R, R-alpha- Alpha-tocopherol inhibits the activity of protein
tocopherol form of the vitamin is stored up to kinase C, an enzyme involved in cell
six times longer than synthetic versions. proliferation and differentiation in smooth
muscle cells, platelets, and monocytes.
Metabolism Vitamin-E–replete endothelial cells lining the
Vitamin E is considered to be metabolized interior surface of blood vessels are better
after it has performed its antioxidant function. able to resist blood-cell components adhering
It is converted from a tocopherol to a to this surface.
tocopherylquinone. The elimination of this end
product is primarily through the feces but a 4) Anti-inflammatory activity
small fraction is removed by urine (less than 1 Vitamin E also increases the expression of
percent). two enzymes that suppress arachidonic acid
In order for tocopherylquinone to be excreted, metabolism, thereby increasing the release of
it first has to be converted to prostacyclin from the endothelium, which, in
tocopherylhydroquinone, a partially reduced turn, dilates blood vessels and inhibits platelet
form. This form can then combine with aggregation.
glucuronic acid so that it can mix with bile.
Bile is removed from the body through feces. 5) Effect on Eye
Age-related macular degeneration (AMD) and
Pharmacological Properties of Vitamin E cataracts are among the most common
The eight chemical forms (alpha-, beta-, causes of significant vision loss in older
gamma-, and delta-tocopherol and alpha-, people. Their etiologies are usually unknown,
beta-, gamma-, and delta-tocotrienol) of but the cumulative effects of oxidative stress
vitamin E that have varying levels of biological have been postulated to play a role. If so,
activity but alpha- (or α-) tocopherol is the nutrients with antioxidant functions, such as
only form that is recognized to meet human vitamin E, could be used to prevent or treat
requirements. these conditions.

1) Antioxidant activity of alpha tocopherol Interactions with Medicaments

Antioxidants protect cells from the damaging Vitamin E supplements have the potential to
effects of free radicals, which are molecules interact with several types of medications. A
that contain an unshared electron. Free few examples are provided below. People
radical’s damage cells and might contribute to taking these and other medications on a
the development of cardiovascular disease regular basis should discuss their vitamin E
and cancer. Unshared electrons are highly intakes with their healthcare providers.
energetic and react rapidly with oxygen to
form reactive oxygen species (ROS). The Anticoagulant and antiplatelet medications
body forms ROS endogenously when it Vitamin E can inhibit platelet aggregation and
converts food to energy. ROS also produced antagonize vitamin K-dependent clotting
when exposed to free radicals from factors. As a result, taking large doses with
environmental exposures such as cigarette anticoagulant or antiplatelet medications,
smoke, air pollution, and ultraviolet radiation such as warfarin (Coumadin®), can increase
from the sun and becomes part of signaling the risk of bleeding, especially in conjunction
mechanisms among cells. with low vitamin K intake. The amounts of
Vitamin E is a fat-soluble antioxidant that supplemental vitamin E needed to produce
stops the production of ROS formed when fat clinically significant effects are unknown but
undergoes oxidation. Scientists are probably exceed 400 IU/day.
investigating whether by limiting free-radical
production and possibly through other
mechanisms, vitamin E helps to prevent or

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Simvastatin and niacin specific applications is sophisticated,

Some people take vitamin E supplements including microencaplication and enrobing
with other antioxidants, such as vitamin C, technologies. For all applications, oxidative
selenium, and beta-carotene. This collection stability of the Vitamin E product is required.
of antioxidant ingredients blunted the rise in Use of microencapsulation or coatings to
high-density lipoprotein (HDL) cholesterol protect tocopherols and tocotrienols by
levels, especially levels of HDL2, the most forming oxygen barriers allows wider use of
cardio protective HDL component, among nonesterified delivery forms.
people treated with a combination of Microencapsulation through spray drying of
simvastatin (brand name Zocor®) and niacin. the vitamin E in presence of various carriers
imparts specific characteristics to the
Chemotherapy and radiotherapy application form including water dispersilibity
Oncologists generally advise against the use of powdered products with good flow
of antioxidant supplements during cancer characteristics.
chemotherapy or radiotherapy because they
might reduce the effectiveness of these Commercial forms include the following
therapies by inhibiting cellular oxidative categories
damage in cancerous cells. Although a 1. Pure Standards
systematic review of randomized controlled Pure standards are readily available for the
trials has called this concern into question, tocopherols from chemical
further research is needed to evaluate the suppliers.Tocotrienol standards are
potential risks and benefits of concurrent commonly available. The United States
antioxidant supplementation with conventional Pharmacopoeia (USP) standard is all-rac-α-
therapies for cancer. tocopheryl acetate. One USP unit of vitamin E
activity of 1 mg of all-rac-α-tocopheryl
Pharmaceutical use of Alpha Tocopherol acetate, 0.67 mg of RRR-α-Tocopherol, or
 Antioxidant 0.74 mg of RRR-α-Tocopheryl acetate. All-
 Solubility Enhancer rac-α-Tocopheryl acetate (USP) is the most
Tocopherols are used as an oil preservative form for fortification of foods and feed and for
to prevent them from going rancid. pharmaceutical use in vitamin supplements. A
In Pharmaceutical formulation like Topical synthesized, all-α-tocopherol acetate is
preparation, Oral liquid preparations, viscous, light yellow oil.
Emulsions, Vitamin E can be used as
Antioxidant or as surfactant to increase the 2. Oils and concentrates
palatability of this formulation forming them Natural source tocopherols, tocotrienol,
stable and enhancing their solubility. RRR-α-rac-tocopheryl esters are available as
Vitamin E is widely used as an inexpensive pure oils and concentrates diluted with edible
antioxidant in cosmetics and foods. Vitamin E oil. Mixed natural source concentrates range
containing products are commonly used in the from 20% by weight to 90% by weight mixed
belief that vitamin E is good for the skin; many tocopherols. Such concentrates are marketed
cosmetics include it, often labeled as as antioxidants for foods and
tocopherol acetate, tocopheryl linoleate or supplements.Tocopheryl esters in oil form are
tocopheryl nicotinate. Vitamin E is often primarily used for fortification of food and feed
claimed by manufacturers of skin creams and because of their oxidative stability.
lotions to play a role in encouraging skin
healing and reducing scarring after injuries 3. Dry, Granular powders
such as burns. Esters of RRR-α-Tocopherol or all-α-
Eg. Limited oral absorption of Paclitaxel as tocopherol can be absorbed onto silicon
Anticancer drug can be increased by using dioxide, microcrystalline cellulose, or modified
Vitamin E as surfactant by forming Self cellulose or spray-dried with suitable carriers
emulsifying drug delivery System or by such as gelatin, dextrin and sugars to
micellar suspensions, microemulsions. produce dry, granular powders. These
powders have good flow characteristics for
Commercial Products of Alpha Tocopherol use in compressed tablets, chewable tablets,
Demand of Vitamin products increased and gelatin capsules. They are not water-
rapidly over the past two decades. Along the dispersible.
market demand, the number of product types
available to the pharmaceutical food, feed,
and cosmetic industries has increased.
Technology to manufacture products for

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4. Water-dispersible Free-Flowing absorption of lipids. Vitamin E TPGS has

Powders amphiphilic properties and forms micelles.
Mixed, natural source tocopherols, RRR-α- Vitamin E TPGS (d-alpha tocopheryl
Tocopherol, Tocopheryl esters are polyethylene glycol 1000 succinate) has
microencapsulated by spray drying the oils become a powerful tool in the formulation of
with various carriers including gelatin, gum lipophilic and poorly soluble compounds and
acacia, and carbohydrates such as dextrin, in enhancing their absorption and
sucrose, or glucose. Vitamin E oil droplets are bioavailability. TPGS has unique properties
embedded in a protective matrix that is water and a proven record of safety and efficacy in
dispersible. Some products are coated with pharmaceutical, nutrition, food and beverage,
starch or modified starch to enhance through personal care and animal nutrition products.
addition of silicon dioxide. Water-dispersible Antares Health Products Inc. focuses
dry products are used in vitamin premixes, for exclusively on serving the market needs for
fortification of liquids and dry products that will TPGS.
be reconstituted. These products are suitable
for use in compressed tablets or gelatin Vitamin E TPGS supplies in water-soluble
matrix multivitamins and mineral form the natural d-α-tocopherol which is
supplements. universally accepted, including the Food and
Drug Administration (FDA), the United States
5. Gelatin Microcapsules Pharmacopeia (USP) and the National
all-rac-α-Tocopheryl acetate is available in Academy of Sciences (NAS) and industry, as
gelatin microcapsules for cosmetic. more potent than the synthetic form dl-α-
tocopherol. Vitamin E TPGS supplies 372-447
6. Water-soluble Vitamin E IU/g from 250-300 mg d-α-tocopherol/g.
Eastman Chemical Company manufactures
water soluble- vitamin E. Chemically, the Use of TPGS as Emulsifier, Solubilizer and
product is synthesized by esterification of Formulation Excipient
polyethylene glycol 1000 onto RRR-α- Vitamin E TPGS has a molecular structure
tocopheryl succinate.The compound is similar to an amphiphile with a polar
marketed as TPGSNF, RRR-α-Tocopheryl hydrophilic head (polyethylene glycol 1000)
succinate. The material is waxy, yellow solid and a lipophilic tail (phytyl chain of d-α-
with the ability, because of its amphiphilic tocopherol). In addition, it exhibits low critical
properties, to form miscible micelles in water. micellar concentration (CMC) and large
Applications include modification of thermal surface area. These characteristics make it a
properties of miscible ois, enhancement of good emulsifier. TPGS can emulsify or help
vitamin E bioavailability in humans and solubilize a wide range of water-oil immiscible
animals, drug absorption enhancement and and other poorly soluble compounds. The
provision of vehicle for drug delivery. The role characteristics above coupled with its ability
as an absorption enhancer is beneficial in the to form various liquid crystalline phases and
treatment of chronic homeostasis. its solubility and stability in water solutions
make TPGS a useful formulation excipient.
The following are important characteristics of
Case Study TPGS relevant to its functions as emulsifier,
TPGS—A Synthetic Source of Vitamin E solubilizer and formulation excipient.
The Micelle of TPGS
Solubility in Water


Critical Micelle Concentration

Micelles are spherical microparticles 0.02 w/w %
composed of amphiphilic molecules (with
hydrophilic head and lipophilic tail). Micelles Particle Size
in aqueous solution sequester in their center Reported particle size diameter ranged from
the hydrophobic tail regions and other less than 1 and up to several microns for
lipophilic compounds. In the human body, liquid emulsions and solid formulations with
formation of micelles is essential for the TPGS.

Vol. 1 (3) Jul-Sep 2012 1031


Manufacturing, Packaging and Storage of Shelf-life

TPGS Antares Vitamin E TPGS FG and NF grades
Manufacturing are labeled with a 4 year shelf -life from the
The manufacturing facility meets current date of manufacturing when stored in the
Good Manufacturing Practices (cGMP) as original sealed unopened container.
outlined in ICH Q7A.
Properties of TPGS
Product Grades Chemical Properties
Food grade (FG) Antares vitamin E TPGS is the polyethylene
The Antares vitamin E TPGS FG exceeds the glycol 1000 ester of d-α-tocopheryl succinate.
requirements for use in dietary supplements It is generally chemically stable with a polar
and foods. hydrophilic head (polyethylene glycol 1000)
end and a lipophilic tail (phytyl chain of d-α-
Pharmaceutical Grade (NF) tocopherol).
The Antares vitamin E TPGS NF meets the
Current Good Manufacturing Practices Chemical Structure
(cGMP) requirements for use in
pharmaceutical formulations. The Antares
vitamin E TPGS NF meets the International
Pharmaceutical Excipients Council (IPEC)
and the Pharmaceutical Quality Group (PQG)
guidelines for pharmaceutical excipients.

Raw materials
Raw materials meet applicable specifications
and standards. Raw materials are certified Chemical Name
and released by Quality Assurance prior to d-α-tocopheryl polyethylene glycol 1000
use in manufacturing. succinate.
Manufacturing process Empirical Formula
The cGMP compliant manufacturing process: C33O5H54 (CH2 CH2O)n
Utilizes ingredients and production equipment
which meet kosher requirements. Utilizes Synonyms/Acronyms
ingredients free of BSE/TSE (Bovine Vitamin E TPGS or TPGS Tocophersolan
Spongiform Encephalopathy/Transmittable (International Nomenclature of Cosmetic
Agents of Animal Spongiform Ingredients – INCI and United States Adopted
Encephalopathy) 1) Utilizes ingredients free Names -USAN).
from removes known allergens. 2) Removes
compounds (such as proteins) that may be CAS Number
changed by genetic modification. Removes 9002-96-4 (Chemical Abstracts Service
Organic Volatile Impurities (OVI). registration number).
Product release Molecular Weight
Antares submits samples from each lot to 1513
independent, fully accredited laboratories for D-α-tocopherol
chemical and microbial analyses which 25% minimum weight basis; range 25-30%.
provides for release of the product for
commercial use if it meets specifications and Acid Value
issues the Certificate of Analysis (COA) which 1.5 (maximum).
along with the Material Safety Data Sheet
(MSDS) accompany each shipment. Reactivity
Reacts with alkali, very low reactivity with air.
Antares Vitamin E TPGS FG and NF grades Physical Properties
are available in 1 kg and 15 kg in tamper- Antares vitamin E TPGS is a pale yellow
evident plastic sealed containers. The water-soluble waxy solid with low melting
containers are heat tolerant to at least 50 °C. point.

Vol. 1 (3) Jul-Sep 2012 1032


serves as an ethanol free, hypoallergenic,

Physical form non-irritating emulsifier/excipient for personal
Waxy solid. care and cosmetic products. It may be used
to solubilize poorly soluble actives. TPGS the
Color International Nomenclature of Cosmetic
White to light tan (as solid) Ingredients (INCI) lists TPGS as
Gardner Color 5. Eye drops, nasal sprays, syrups and
Less than 10 (generally less than 5) others primarily in formulating active
Specific Gravity 6. Creams, lotions and other products for
1.06 at 45°C, approximate topical application of vitamin E and other
Melting Point formulated actives.
38 °C approximate (range 37-41)
2) TPGS Used In Animal Nutrition
Solubility In water  TPGS can be used in high vitamin E
Soluble (up to 20 weight %) supplements in the form of liquid, powder, gel,
tablet, blocks and other forms of animal
Specific Rotation [α] supplements.
Not less than +24.  Premixes, concentrates and other forms
that can be used in the fortification of animal
Amphiphilic (Surface-Active) Properties feeds.
Vitamin E TPGS has amphiphile properties
with a polar hydrophilic head (polyethylene 3) Use of TPGS in Dietary Supplements.
glycol 1000) and a lipophilic tail (phytyl chain  Liquid vitamin E or liquid
of d-α-tocopherol). As an amphiphile, TPGS multivitamin/mineral supplements. As water
is useful emulsifier of lipids and helps soluble, TPGS is preferable over the oil forms
solubilize poorly soluble compounds. In of vitamin E especially in water based liquid
addition, it forms micelle like particles which products.
increase absorption and bioavailability.  Other forms of vitamin E or liquid
multivitamin/mineral dietary supplements
Application of TPGS such as tablets, softgels, bars and others.
 Pharmaceutical Application 4) Use of TPGS in Food and Beverage
1. TPGS is water soluble, has a molecular  Vitamin E TPGS is an approved form
structure similar to an amphiphile, exhibits low of vitamin E and may be used to fortify foods
critical micellar concentration (CMC) and and especially beverages, sports drinks,
large surface area. These characteristics juices and water.
make it a good emulsifier. TPGS can emulsify
or help solubilize a wide range of water-oil Pharmaceutical Formulations of Alpha
immiscible and other poorly soluble APIs trial. Tocopherol
2. The characteristics above coupled with its 1. Emulsion
ability to form various liquid crystalline phases Another study reported the formulation of filter
and stability in water solutions enable TPGS sterilizable emulsion formulation of paclitaxel
to serve in drug delivery/controlled release using á-tocopherol as the oil phase and á
systems. tocopherylpolyethyleneglycol-1000 succinate
3. Enhances absorption of and (TGPS) and poloxamer 407 as emulsifiers.
bioavailability especially of poorly soluble The formulation exhibited better efficacy and
APIs and in malabsorbing patients due to its was more tolerable when studied in B16
emulsifying/solubilizing properties and its melanoma tumor model in mice.
ability to form micelle like particles and affect
the absorption mechanisms. 2. SEDDS (Self Emulsifying Drug Delivery
4. The major applications of vitamin E TPGS System)
in pharmaceutical formulations include, Silybin, the principal component of a Carduus
Solubilization and formulation of lipophilic and marianus extract, is known to be very
poorly soluble APIs including cyclosporine, effective in protecting liver cells from harmful
amprenavir and paclitaxel, Vitamin E TPGS is effects caused by smoking, drinking,
finding applications in personal care and overworking, environmental contaminants,
cosmetic products. In addition to providing stress or liver-damaging drugs. However, the
water-soluble vitamin E, it is a powerful tool in bioavailability of orally administered Silybin is
formulating other actives. Specifically, TPGS very low due to its low solubility in water. Woo

Vol. 1 (3) Jul-Sep 2012 1033


et al. discloses an oral microemulsions chemistry to characterize chemical changes

consisting of a Carduus marianus extract induced by microwave heating compared to
containing a major amount of Silybin, or a conventional processes. In this line, extensive
Silybin derivative as an active ingredient. The work has been conducted to define the effect
composition of the invention consists of of microwave energy on oxidation, oxidative
Miglyol 812 and ethyl linoleate as oils, HCO stability of vitamin E components of
50 and Tween 20 as surfactant, dimethyl microwave processed foods.
isosorbide as co-surfactant and D-tocopherol Conventional work is done by Yoshida and
as an anti-oxidant. The formulation provides a colleagues to determine the effect of the
greatly increased level of in vivo bioavailability microwave on the antioxidative properties of
of silybin, the level being at least 4-fold higher vitamin E .This work was done on heating of
than that achievable by conventional soyabeans before production of full-fat flour,
formulations quantity of seed oils during microwave
treatment, and antioxidative efficiencies of
3. Liposomal Budesonide for Dry Powder tocopherols in oils during microwave heating .
Inhaler: Preparation and Stabilization Conclusions drawn from experiment-
Mayank R. Joshi, and Ambikanandhan Misra 1. In tocopherol stripped oils containing added
Pharmacy Department, Faculty of Technology back tocopherol, the order of stability was
and Engineering, Kalabhavan, P.O. Box No. detected as δ-T>β-T>γ-T>α-T.
51, M.S. University of Baroda, Vadodara- 2. Free fatty esteric chain of Tocopherol is
390001 (Gujarat), India. responsible for the reduction of the
Preparation of liposomes - Multilamellar Tocopherol levels due to the microwave
vesicles (MLVs) of BUD were prepared by the bombardment.
modified Bangham method, Drug (5 mg), 3. In more saturated animal fats, the 12 min of
EPC, CHOL, and α-tocopherol (1% of EPC) microwave heating. Peroxides values,
were co-precipitated to a thin film , using a carbonyl values, and anisidine values
solvent system (CHCl3:CH3OH [2:1], 10 mL) increased, showing that antioxidant capacity
for a solvent stripping technique in a rotary can be overcome quite easily during
flask evaporator under vacuum in a nitrogen microwave heating.
atmosphere. The dried film was then hydrated 4. As the bombardment of microwave
at 25 ± 2°C for 1 hour with 5 mL of phosphate increases the oxidation of the soyabean takes
buffer saline, pH 7.4 (0.17 µ ionic strength), place with the loss of Tocopherol.
containing 1 mM EDTA and 500 mM sucrose.
Liposomal dispersion thus formed was Visible radiation and Ultraviolet Radiation
subjected to sonication under nitrogen Due to the low bombardment capacity of the
atmosphere in an ice bath for 30 minutes. Uv-Visible radiations they can be used for the
Sonicated vesicles were further stabilized by surface treatment for killing microorganisms.
hydration for 8 hours at ambient temperature
and separated from free drug by Irradiation
centrifugation. The liposomal dispersion of Food irradiation in case of the green
BUD so obtained was filled in an amber- vegetables is the process of the exposing
colored vial under nitrogen atmosphere and food to radiant energy to reduce or eliminate
sealed and stored in a refrigerator. bacteria making it safer and more resistant to
spoilage. Radiation energy includes
Stability of Alpha Tocopherol Microwave radiation, infrared, ultra-violet
Microwave Radiation radiation, light and ionizing radiation. Due to
Microwave heating varies from conventional chemical changes produced in food.
heating in which heat is generated by
molecular excitation resulting from friction Evaluation of Formulation Containing
from the interaction of an electromagnetic Alpha Tocopherol
field with chemical components of the food. Case Study
Due to advantage of time energy savings, A potential tocopherol acetate loaded
excellent control, and convenience, in palm oil esters-in-water nanoemulsions for
comparison to conventional heat processing Nanocosmeceuticals.
widely used for particularly drying
applications. Additionally, laboratory use is Abstract
rapidly increasing to speed extractions and Cosmeceuticals are cosmetic-pharmaceutical
organic synthesis processes; because of the hybrids intended to enhance health and
speed and frictional heat generation, research beauty of the skin. Nanocosmeceuticals use
has been conducted in many areas of food nano-sized system for the delivery of active

Vol. 1 (3) Jul-Sep 2012 1034


ingredients to the targeted cells for better This technology utilizes nano-sized particles
penetration. In this work, Nanoemulsion from for better penetration as compared to
palm oil esters was developed as a delivery traditional cosmetics which results in the
system to produce Nanocosmeceuticals. The production of nanocosmeceuticals. In
stability of the resulting formulation was addition, the effect of additive i.e. Vitamin E
tested using various methods. In addition, the on the stability of the formulations was also
effect of components i.e. Vitamin E on the studied. Materials used are Nonionic
formulation was also studied. Vitamin E was surfactant; Polysorbat 80 (Tween 80) .The
found to co-emulsify and co-stabilized the polymeric surfactant 10% (w/w) solution of
formulations. The best formulation was found Pluronic F-68. The active ingredient, DL-α-
to be the one having the composition of 10% Tocopherol Acetate (Vitamin E), is an
Palm Oil Esters (POEs), 10% vitamin E, 24% antioxidant. Water was deionised by Milli-Q
Tween 80, 2.4% Pluronic F-68 and 53.6% filtration.
deionised water. Those compositions are
considered to be the best as a Analytical Profile of Alpha Tocopherol
nanocosmeceuticals product due to the small Bunnel in a 1971 review of procedures for
particle size (94.21 nm), low occurrence of analysis of vitamin E stated that “New or
Ostwald ripening and stable at different modified analytical methods are most reliable
storing temperatures (5, 25 and 45°C) for four for the development for analytical profile of
weeks. Palm oil esters-in-water Tocopherol. He developed Gas
nanoemulsions loaded with vitamin E was chromatography, High performance Liquid
successfully formulated and has the potential chromatography, which gives best approach
for the use as nanocosmeceuticals. Some of for quantification of Tocopherol and
the nanotechnology-based innovations such Tocotrienols.Bunnel also reviewed the other
as nanoemulsions, nano-capsules, nano- chromatographic techniques such as Paper
pigments and liposomes are widely used in chromatography, thin layer chromatography,
various type of cosmetic products .Solè et. al. Column chromatography. Emmerie-Engel or
(2006) defines nanoemulsions as emulsion bathophenthroline reagents were usually
systems having particle sizes ranging from 20 employed for chromophore development.
- 500 nm. Due to the small droplet sizes, Parrish in 1980 classified methods for vitamin
nanoemulsions are believed to be stable E analysis into the following categories.
against creaming or sedimentation, 1) Biologicals assays: Fertility tests including
flocculation and coalescence .However,  Resorption-gestation
Tadros, 2005 also stated that nanoemulsions  Development of encephalomalacia in
are vulnerable to instability caused by newly hatched chicks
Ostwald ripening. Vitamin E is the most  Development of muscular dystrophy
renowned anti-oxidant known to and creatinuria in rabbits
cosmeceuticals. It is lipid soluble and it helps  Vitamin E content of blood or liver
in protecting membrane lipids from various species hemolysis of red blood cells
peroxidation when taken orally. Furthermore, in vitamin E deficient rats.
it has been shown to decrease sunburn cells 1) Physicochemical methods: Ultraviolet
after UV exposure, neutralize free radicals, (UV), Fluorometric,and, and, and colorimetric
and also act as a humectants when vitamin E methods.
is applied on the skin. Although much effort 2) Chromatographic methods: Paper,
has been concentrated on formulating thin-layer, column, gas chromatography and
cosmeceuticals, little has been done to HPLC.
incorporate nanotechnology into But among above all methods Gas
cosmeceuticals products. The purpose of this chromatography and High Performance liquid
research was to formulate stable chromatography are most reliable than other
nanoemulsions system containing vitamin E. above mentioned methods.

Vol. 1 (3) Jul-Sep 2012 1035


Table 4: Historical Significant Methodology Publications for the Analysis of Vitamin E

Method Approach References
Biological Assays Feed basal diet deficient in vitamin E to young
Resorption-gestation female rats until 34-40 days of age breed Joffe andHarris,1943
pregnant females are fed graded doses of test Mason and Harris 1947
material or vitamin E standards, rats are killed
after 16 days gestation, dead and live fetuses
are counted
Encephalomalacia in chicks Newly hatched chicks are fed a Vit.E-free diet Dam and,sondergaard 1964
feeds and standards are fed from the 4 day
after hatching ,record deaths occurring in 7 to 10
Muscular dystrophy in rabbits Muscular dystrophy symptoms occurs after 1 Hove and Harris 1947 Fitch and Diehl
month with vitamin E deficient diets, standard 1965
and test diets lead to improvements; rabbits die if
Vitamin E not added to diet
Hemolysis of red blood cells in Young rats(100g) are fed a vitamin deficient diet Rose and Gorgy 1952
rats for 3-4 weeks until red blood for cells show>90% Horwitt et al 1956
hemolysis; hemolysis is in vitro with dialuric acid
or hydrogen peroxide; Vitamin E test doses are
administered by stomach tube; biopotency is
measured from the reduction in the red blood cell
hemolysis of test group compared to that of
deficient group.
Physicochemical methods Direct spectrophotometric determination; limited
UV-Spectroscopy to pure solutions or high concentration Lambertsen and brackkn 1959
Colorimetric Emmeric-Engel reaction; based on the reduction Emmeric and Engel 1938
of ferric ions to ferrous ions; which forms a red Emmeric 1940
complex with α-2’-dipyridine; measure at 520 nm;
modification uses bathophenanthroline.
Fluorescence Free tocopherols fluoresce strongly; esters Duggan 1959
fluoresce weakly; primary detection mode for Thompson et al 1972
Hplc assays
Chromatographic paper One and two dimensional chromatography on Brown 1952
paper impregnated with petroleum, paraffin or Eggitt and Ward 1953
zinc carbonate; solvent systems are benzene, Green et al 1955
benzene cyclohexane,diethyle ether-petroleum
Thin layer chromatography One and two dimensional chromatography on Scher 1961
alumina, magnesium sulphate,silica gel Calcium Dilley and crane 1963
phosphate, and diatomaceous earth; mobile Stowe 1963
phases similar to those used in paper Ames 1971
chromatography; detection by spray with Lovelady 1973
Emmeric-Engel reagent, antimony
pentachloride,UV,or Fluorescence.
Column chromatography Primarily used as a cleanup step before other Drummond et al 1935
determine steps such as GC commonly used Emmerie and Engel 1939
solid phase materials include magnesium Kofler 1947
phosphate,celite,florisil,silica gel alumina, Fuller’s Bieri et al 1961
earth,hydroxyalkoxypropyl sephadex. Dicks-Bushnell 1967
Strong 1976
Gas-Liquid chromatography Volatile derivatives are usually formed; capillary Nicolaids 1960
GC has many advantages over packed column Wilson et al 1962
chromatography, detection is with FID; Nair and Turner 1963
methodology is still useful but most routine Nelson and Milun 1968
assays are completed by HPLC. Lehmann and Slover 1971Feeter 1974
Slover and Thompson 1981
High Performance Liquid Normal phase and Reversed phase Schmt et al 1971
Chromatography chromatography detection UV of fluorescence; Van Niekerk 1973
normal phase chromatography can resolve the Vatassery et al 1978
eight vitamin E forms ; reversed phase cannot Ruggeri et al 1979
resolve the positional isomers;β-Tocopherol and Barns and Taylor 1980
α-Tocopherol; most widely applicable easily
controlled assay approach for analysis of Vitamin

Vol. 1 (3) Jul-Sep 2012 1036


Determination of Αlpha - Tocopherol an injection port (preferably glass-lined) using

Acetate By Gas Chromatography an automatic injection device or some other
Early Gas chromatography procedures for reproducible injection method. Measure the
Vitamin E analysis has used packed columns; peak areas by electronic integration of the
stationary phases including Apiezone L, SE- reference solution. Repeat this operation until
30, and OV-17; and Flame ionization the response factor (RF) determined as
detection. In most of the methods tocopherols described below is constant to within + 2 per
and tocotrienols were derivatized to their cent. The resolution (Rs) between the
trimethylsilyl ethers to improve thermal dotriacontane peak and the α-tocopherol
stability and volatility. acetate peak is at least 1.4.

Assay Parameter Interference test

Vitamin E Weigh accurately a quantity of the substance
to be examined corresponding to about 0.100
Principle g of α-tocopherol acetate in a 250 ml conical
Gas chromatography using dotriacontane as flask. Add 20ml of 1 M hydrochloric acid and
the internal standard. treat with ultrasound at 70 for 20 min. Add 50
ml of ethanol and 50 ml of hexane and
Internal standard solution thoroughly mix the two phases for 30 min.
Dissolve 0.20 g of dotriacontane in hexane Allow to separate. Inject 1 ml of the upper
and dilute to 100.0 ml with the same solvent. layer and record the chromatogram, choosing
an attenuation such that the height of the
Test solution peak corresponding to tocopherol acetate is
Weigh accurately a quantity of the preparation greater than 50 per cent of the maximum
to be examined corresponding to about 0.100 recorder response; during the recording,
g of α-tocopherol acetate in a 250 ml conical change the attenuation so that any peak
flask. Add 20 ml of 1 M hydrochloric acid and appearing with the same tR value as for
treat with ultrasound at 70 for 20 min. Add 50 dotriacontane is recorded with a sensitivity at
ml of ethanol and 50.0 ml of the internal least eight times greater than for the α-
standard solution and thoroughly mix the two tocopherol acetate peak.
phases for 30 min. Allow to separate, and use If a peak with a height of at least 5 mm for a
the upper layer assay recorder paper width of 250 mm is detected
with the same tR value as for dotriacontane,
Reference solution use the corrected peak area S'D (corr.) For
Dissolve 0.100 g of alpha-tocopherol acetate the final calculation.
in the internal standard solution and dilute to
50.0 ml with the internal standard solution. S′D (corr) = S′D – SI x S′Tƒ x STI

The chromatographic procedure may be S'D = area of the peak corresponding to the
carried out using internal standard in the chromatogram
a) A silanised glass column 2.0 m to 3.0 m obtained with the test solution,
long and 2.2 mm to 4.0 mm in internal Sl = area of the interfering peak (same tR
diameter packed with diatomaceous earth for value as that of the internal standard) in the
gas chromatography (125 to150 cm or 150 to chromatogram obtained in the interference
180cm), silanised with dimethyldichlorosilane test,
and impregnated with 1 per cent m/m to 5 per S'T = area of the peak corresponding to α-
cent m/m of poly (dimethyl) siloxane; a plug of tocopherol acetate in the chromatogram
silanised glass wool is placed at each end of obtained with the test solution,
the column STI = area of the peak corresponding to α-
b) Nitrogen for chromatography as the carrier tocopherol acetate in the chromatogram
gas at a flow rate of 25-90 ml/min, obtained in the interference test,
c) A flame-ionization detector. f = factor by which the attenuation was
Maintaining the column at a constant changed.
temperature between 2450C and 2800 C and Inject 1 ml of the reference solution and
the injection port and the detector each at a record the chromatogram, choosing
0 0
constant temperature between 270 and 320 attenuation such that the peak corresponding
C.Set the temperature of the column and the to α-tocopherol acetate is greater than 50 per
flow rate of the carrier gas in such a manner cent of the maximum recorder response.
that the required resolution is achieved. Make Measure the areas of the peaks
the injections directly onto the column or via corresponding to α-tocopherol acetate (ST)

Vol. 1 (3) Jul-Sep 2012 1037


and to dotriacontane (SD) and determine the micelles, resulting into increased resolution
response factor (RF) as described below. times. In MKEC pseudo-stationary phase
Inject 1 ml of the test solution in the same used is the Tetradecylammonium ions for
manner. Measure the areas of the peaks greater resolution of all rac-α-tocopherols.
corresponding to α-tocopherol acetate (S'T) Capillary electrochomatography (CEC) can be
and to dotriacontane (S'D). done with LC and CZE.Abidi and rennick
Determine the response factor (RF) for α- compared CEC on C8 and C18 and phenyl
tocopherol acetate in the chromatogram reversed phase supports with different mobile
obtained with the reference solution from the phases. Optimum resolution was done by
areas of the peak corresponding to α- using acetonitrile-methanol (64:36), 25mM tris
tocopherol acetate and the peak (hydroxymethyle) amino methane, pH 8.0 as
corresponding to dotriacontane using the mobile phase. Separation voltage is about
expression: 25kV at 30.
SD x m T S T x m D
Calculate the percentage content of α- Gas-chromatography/Mass
tocopherol acetate using the expression: chromatography
100 x S'T x m D x RF where GC/MS technique can be used to study
S' D (corr) x m absorption, deposition, metabolism of all fat
SD= area of the peak corresponding to the soluble vitamins. Melchert and Pabel showed
internal standard in the chromatogram in 2000 that GC/MS based on simple
obtained with the reference solution, extraction of serum using SPE (extrelut) and
S'D (corr.) = corrected area of the peak chromatography on silica gel.
corresponding to the internal standard in the
chromatogram obtained with the test solution, Liquid chromatography /Mass
ST= area of the peak corresponding to α- chromatography
tocopherol acetate in the chromatogram Application of LC/MS to analysis of vitamin E
obtained with the reference solution, has been achieved with particle beam,
S'T= area of the peak corresponding to α- electrospray, ion spray. Rental et al increased
tocopherol acetate in the chromatogram sensitivity of MS for tocopherols by addition of
obtained with the test solution, silver ions to eluent of LC to form
mD= mass of the internal standard in the test Ag+Tocopherol adducts that facilitated
solution and in the reference solution in ionization.
mT = mass of a-tocopherol acetate in the Example of Commercial Alpha Tocopherol
reference solution in milligrams, SolarToco TM Natural Tocopherol
m = mass of the substance to be examined in Vita-Solar Biotechnology manufactures and
the test solution in milligrams. markets a line of plant sterol
Products under the brand name SolarToco™.
Additional Analytical Approaches to
Vitamin E Product Description
Electrophoretic Methods Vitamin E deficiency occurs as a result of rare
Capillary electrophoresis (CE) applied as genetic abnormalities affecting
capillary zone electrophoresis (CZE) or the alpha-tocopherol transfer protein (alpha-
Micellar electrokinetic capillary TTP), as a result of various malabsorption
chromatography which is established method syndromes and as a result of protein-energy
to quantify vitamins in pharmaceutical malnutrition. Alpha-TTP is a protein found in
products.Trenerry stated that Capillary the liver, heart, cerebellum and retina. Alpha-
electrophoresis is faster, more efficient, and TTP selectively recognizes alpha-tocopherol
cost effective compared to traditional methods and is believed to mediate the secretion of
but lack of sensitivity as LC. Normally alpha-tocopherol taken up by the liver cells
problem associated with the CE is that the into the circulation.
food extracts are having incompatibility with
the solvents used in CE.MEKC is used to I .Mixed Tocopherols
separate the neutral molecules on the basis Mixed Tocopherols Concentrate is a reddish-
of the partitioning between an aqueous brown to pale yellow, clear oily liquid,
electrolyte and pseudo-stationary phase of suspension with smaller crystalline is
charged micelles.MKEC is most reliable than permitted, with special taste and smell. Used
CZE for fat soluble vitamins analysis because as antioxidant and nutrient in foods, typical
hydrophobic characteristic of fat soluble doses for supplementation of low alpha mixed
vitamins cause strong interactions with the

Vol. 1 (3) Jul-Sep 2012 1038


tocopherol are around 200mg/daily, Recommended doses for supplementation

determined as d-gamma-tocopherol. range from 100 to 400 milligrams daily with a
cap of 1000 milligrams/day for d-alpha-
II.d-alpha tocopherol tocopherol in the form of d-alpha-tocopheryl
δ -alpha-tocopherol is available as a stand- acetate or succinate. The average intake of
alone supplement and in the form of mixed alpha-tocopherol derived from various dietary
tocopherols. D-alpha-tocopherol is surveys ranges from about 7.5 to 10.3
unesterified and thus much more susceptible milligrams daily for men and 5.4 to7.3
to oxidation. It should be stored in a tightly milligrams daily for women.
closed, opaque bottle and in a cool, dry place.
Typical doses for supplementation range from REFERENCES
100 to 400 milligrams daily. d-alpha- 1. Deb AC. Fundamentals of
tocopherol is also available for cosmetic Biochemistry. 185-189.
application as an antioxidant and moisturizer. 2. U.Santynarayana and U.Chakrapani
Some are hypersensitive to topical d-alpha- “Biochemistry “Books and Allied (P)
tocopherol and may develop dermatitis from Ltd.117.
its use. 3. Wikipedia, The free Encyclopedia.
Chemical Formula: C29H50O2; Molecular 4. WH Schopfer and NL Noecker
Weight: 430.71. “Plants and Vitamines “Asiatic
Publishing house Delhi. 45-46
III.d alpha tocopheryl acetate 5. John H Block and John M Beale
D-alpha-tocopheryl acetate is available as a “Wilson and Gilsvoid Text book of
stand-alone supplement and in multivitamin Organic medicinal and
preparations. Since the acetate group Pharmaceutical Chemistry”, Seventh
protects the hydroxyl group of the chromanol edition, Lippincott Williams and
ring against oxidation, it is a more stable form Wilkins Publication, 879-882.
than d-alpha tocopherol, the free or 6. Indian Pharmacopoeia Vol.II,
unesterified form. Published by the Controller of
Typical doses for supplementation range from Publication Delhi, 767-768.
100 to 400 milligrams daily (as d-alpha- 7. United State Pharmacopoeia 2005,
tocopherol). Asian Edition,
IV. D-alpha tocopheryl succinate 8,2143,2176
D-Alpha-tocopheryl succinate is available as 8. JG.Salway. Medical Biochemistry at
a stand-alone supplement and in combination a glance 2nd Edition, 118.
vitamin preparations. Since the succinate 9. Ronal Eitenmiller and Junsoo Lee.
group protects the hydroxyl group of the Vitamin E Food, Chemisty,
chromanol ring against oxidation, it is a more Composition, and Analysis Marcel
stable form than d-alpha-tocopherol, the free Dekker Publication, 1to19, 322-395.
or unesterified form. 10.
Typical doses for supplementation range from 11. Combs Gerald. The vitamins:
100 to 400 milligrams daily. fundamental aspects in nutrition and
health. San Diego: Academic Press,
Chemical Formula 1992.
C33H54O5, Molecualr Weight: 530.79. 12. Rucker Robert. Handbook of
vitamins. 3rd edition and expanded.
Advantages New York: Marcel Dekker, 2001.
GMO-free and based on non-allergenic 13. DeLuca Hector. The Fat-soluble
ingredients ; High Biological Activity. vitamins. New York: Plenum Press,
Dosage and Administration 14. Antares Health Products, 970
The new RDA for natural alpha-tocopherol for Douglas Road, Batavia, illnois 6051
both men and women is 15
mg/day.30mg/day. To convert from milligrams of
to International Units (UI), the conversion Nanobiotechnology.2010;8:4doi:10.1
factor is 1.49. Therefore, 15 milligrams of 186/1477-3155-8-4
alpha-tocopherol is equal to 22.4 IU. The UL 15. USPTO- United States Patent
for vitamin E is 1,000 milligrams or 1,490 Application 20080311204.
IU/day expressed as alpha-tocopherol.

Vol. 1 (3) Jul-Sep 2012 1039

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