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Stability of vitamin E and vitamin E acetate containing cosmetic preparations


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Tocopherol (T) and tocopherol acetate (TA) are widely used ingredients in cosmetics. The present study was carried out to evaluate the content and stability of T/ TA contained in marketed and experimental cosmetic formulations. T/TA in four marketed products (A-D) and two experimental formulations (F1and F2), stored under different temperatures, were investigated by HPLC. The results indicated variable degree of stability according to the storage temperature and product type. The stability progressively decreased upon storage at 37 °C > 25 °C > 2-8 °C. TA containing formulations showed higher stability compared to T. Further studies are in progress to optimize such formulations for improving vitamin E stability and transdermal permeation to eventually achieve the expected therapeutic and cosmetic outcomes. © 2009, JGPT.
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ISSN 0975 8542
Journal of Global Pharma Technology
© 2009, JGPT. All Rights Reserved.
Nada A.H.*, Zaghloul A.A., Hedaya M.A., Khattab I.S.
Faculty of Pharmacy, Kuwait University, Kuwait
*For Correspondence: E-mail:
Abstract: Tocopherol (T) and tocopherol acetate (TA) are widely used ingredients in cosmetics. The present
study was carried out to evaluate the content and stability of T/ TA contained in marketed and experimental
cosmetic formulations. T/TA in four marketed products (A-D) and two experimental formulations (F1and
F2), stored under different temperatures, were investigated by HPLC. The results indicated variable degree of
stability according to the storage temperature and product type. The stability progressively decreased upon
storage at 37 °C > 25 °C > 2-8 °C. TA containing formulations showed higher stability compared to T.
Further studies are in progress to optimize such formulations for improving vitamin E stability and
transdermal permeation to eventually achieve the expected therapeutic and cosmetic outcomes.
Keywords: Vitamin E, Vitamin E acetate, Commercial cosmetics, Experimental preparations, Stability.
Inclusion of botanical extracts, vitamins,
anti-microbials, etc. to cosmetics has
become an important marketing advantage,
mostly without scientific proof. Claims
based on these additives must be carefully
phrased to maintain the product(s) in the
cosmetic area. In addition, such claims are
rarely based on rigorous scientific
evidence of performance. A case in point
is the use of different components of green
tea for antioxidant purposes on the skin
surface. Although these substances exhibit
systemic effects upon ingestion, evidence
for skin benefits from topical application
has not been established [1]. Topical over-
the-counter products alleged to benefit
ageing skin are immensely popular among
cosmetics consumers. Patients often seek
over-the-counter products due to market
availability, comparably cheaper prices,
and the lack of the physician
bottleneck.Vitami E (-tocopherol, T) is
one of the widely used ingredients in OTC
products for protection against skin
ageing. Vitamin E is a lipid-soluble
antioxidant which plays key roles in
protecting cell membranes from lipid
peroxidation by free radicals [2,3].
Furthermore, Gensler and Magdaleno,
1991 [4] concluded that, in terms of
parameters of tumor incidence and tumor
burden, α-tochopherol significantly
reduced photocarcinogenesis. The term
vitamin E embraces all tocophenols and
tocotrienols showing the biological
activity of the isomer RRR-α-tocopherol
[2]. Vitamin E is normally distributed in
skin, with the highest levels in the deepest
layers [5]. It has been documented that -
tocopherol is the major antioxidant in the
human epidermis, and that its depletion is
an early and sensitive marker of
environmental oxidative damage [6].
Vitamin E topical applications have been
demonstrated to increase stratum corneum
hydration and enhance water binding
capacity [3]. However, the stratum
corneum represents the major barrier
against drug delivery and considered the
limiting factor to permeation of drugs
across the skin [7]. Ricciarelli et al., 1999
[8] pointed out that -tocopherol reduced
the age-dependent increase of collagenase
expression by inhibiting protein kinase C
Nada AH et al., Journal of Global Pharma Technology. 2012; 4(03):1-8
© 2009, JGPT. All Rights Reserved.
activity. The protective effects of vitamin
E against photoaging have been
demonstrated in various animal and in
vitro skin models [9-11]. Proposed
mechanisms for antiaging effects on skin
range from antioxidant properties to
improved collagen synthesis or protection
from collagen breakdown. Despite the
media attention and consumer popularity
that these ingredients have generated, there
have been few scientific studies to support
these claims [12]. Vitamin E is available
as the free alcohol or its esters in
commercial cosmetic formulations.
However, successful delivery of topically
administered ingredients and liberation of
the active form (-tocopherol) is of crucial
value for the efficacy of such preparations.
This fact was demonstrated in a human
study, in which the acetate ester of
tocopherol showed no evidence of
conversion to the biologically active form,
-tocopherol, despite adequate absorption
into the skin [13]. Furthermore, a recent
study on the metabolic conversion of -
tocopherol acetate (TA) into -tocopherol
in skin demonstrated that permeation and
metabolism of -tocopherol acetate was
highly dependent on the delivery system,
re-emphasizing the importance of
formulation in cosmetic preparations [14].
The importance of actives vs. inactive
forms, appropriate concentration,
consistent delivery and product stability
remain hurdles which most of the
published literature has yet to cross.
Although cosmetics and cosmeceuticals
are tested for safety, testing to determine
whether beneficial ingredients actually live
up to a manufacturer’s claims is not
mandatory [15]. Accordingly, academia
and state agencies should contribute in
reviewing and verifying the claims made
by manufacturers to protect the consumers
and ensure valid and scientifically founded
claims for cosmetic products. Furthermore,
the fast oxidiziable T and TA in the
marketed cosmetic products present a
scientific challenge on the optimal storage
conditions. Thus, the objectives of the
present study were to assess the content
and effect of storage condition on vitamin
content of such cosmetic preparations for
determining the optimum storage
conditions. This investigation aims at
determination of vitamin E/acetate in 4
commercially available cosmetic products
in Kuwaiti Market (A, B, C, and D) and
two experimental cosmetic formulations
(F1 and F2), as well as evaluation of
vitamin stability in the above products.
Methanol, acetonitrile, hexane and ethanol
used in the study were of HPLC grade
(Merck, Darmstadt, Germany). Vitamin E
Acetate was obtained from BASF
Ludwigshafen, Germany. Vitamin E,
soybean oil and corn oil were procured
from Sigma Aldrich Chemie GmbH,
Steinheim, Germany. Propylene glycol
(Generico Medical Practice, AB Almere,
Holland), stearic acid, white soft paraffin,
potassium hydroxide (Loba CHEMIE-
India), lanoline, glycerol, sorbitol
(Gainland Chemical Company, UK),
Captex SBE and Acconon S-35 (ABITEC
Corporation, Janesville, USA). All other
chemicals used were of analytical grade.
Commercial cosmetic products
Four commercial products (A, B, C and D)
were obtained from retail pharmacies in
Kuwait and they contained only TA
without declaration of its quantity. The
study was conducted before reaching the
expiry dates. No products containing T
were found in the market and, therefore,
the experimental lab formulations were
prepared to study the stability of T as well
as to serve for evaluation of extraction
method for analysis.
Preparation of Vitamin E-containing
laboratory products
Two cream-emulsion cosmetic
formulations (Table 1), each containing
about 0.5%w/w of T/TA, were prepared in
Nada AH et al., Journal of Global Pharma Technology. 2012; 4(03):1-8
© 2009, JGPT. All Rights Reserved.
the laboratory to simulate the complex
composition of commercial cosmetic
preparations. The cream was prepared by
melting stearic acid in a porcelain dish
over water bath (75-80 ˚C), then the
semisolid ingredients (lanoline, white soft
paraffin and Captex SBE) were added until
all the mixture is melted, and finally
soybean oil and corn oil were added (oily
phase). Potassium hydroxide was
dissolved in water followed by Acconon
S-35, then glycerin and sorbitol were
added and the mixture was heated to 75-
80˚C (aqueous phase). The aqueous phase
was added to the oily phase with trituration
and the mixture was then removed from
water bath and mixing was continued until
a homogenous creamy liquid was
obtained. Accurately weighed amounts of
T and TA were added to the mixture,
avoiding addition of the vitamin to the
cream while hot to avoid possible
degradation; resulting in nominal
concentration of 0.532 and 0.539% w/w,
respectively. The final cream was filled in
a well-closed plastic jars.
Method of Extraction of Vitamin E/
Acetate from Cosmetic Products
A 500 mg sample of each formulation was
extracted with methanol, centrifuged, and
the supernatant of extract was filtered
through 0.45 µm cellulose filter and
injected into the HPLC for estimating T
and TA [16].
HPLC Method for the Estimation of T
and TA
The method involved Waters 2690 HPLC
(Waters 2690 Seprations Module Milford
, MA , USA) with variable wavelength
PDA detector, a disposable guard column
C-18 and RP Waters Symmetry C-18
column (4.6 X 150mm, 5 m particle
size). The column temperature was
maintained at 25º C. Samples (50 µl) were
injected and the flow rate of the mobile
phase (3%v/v water/methanol) was
adjusted at 1.5 ml/ min. The eluents were
monitored at 290 nm and 283 nm for T and
TA, respectively. The peak areas for T and
TA were recorded, and analyzed using the
Millennium Software Empower from
Waters. The peak areas of T and TA were
subjected to regression analysis against
their concentrations. The details of the
procedure and validation of the method
was reported previously [16]. The
reported HPLC analytical method was
precise (inter- and intraday variation was
less than 3.5%) and accurate (> 98% of
recovery after adding known quantity of T
and TA to cosmetic products).
Stability of Commercial and
Experimental Products
Three sets of each of the commercial and
developed products were stored at
different temperatures; namely 2- 8C
(refrigerator), 22-25C (shelf), and 37C.
The aged preparations were monitored
visually for physical change, if any, such
as color, odor, and homogeneity and
package integrity. For evaluation of
chemical stability, samples were taken at
zero time, and after appropriate time
intervals, followed by extraction as
described above, and analyzed for vitamin
E / vitamin E acetate content as described
earlier [16]. To study the effect of repeated
exposure of the products to outside
environment on vitamin stability
(simulating real use conditions), samples
were kept in individual vials, each vial
opened and used once for analysis at each
storage time interval, and results were
compared with those obtained from
original bulk containers. Furthermore,
samples were removed from the top
surface of the bulk container and
compared with samples withdrawn from
the interior of the same container to assess
the difference in vitamin oxidation due to
repeated exposure of the product to
surrounding environment (simulating the
real condition of use by consumers).
Nada AH et al., Journal of Global Pharma Technology. 2012; 4(03):1-8
© 2009, JGPT. All Rights Reserved.
Evaluation of Vitamin E Content in
Commercial Products
Market survey in Kuwait regarding
vitamin E/ester-containing cosmetic
preparations revealed that no one product
carry a quantitative claim of the vitamin
content and all products contain only TA.
Four commercial products containing TA
were chosen for the purpose of evaluation
of content and stability upon storage at
three different temperature levels. Analysis
of the commercial products revealed that
the initial concentration of the vitamin
ester (TA) ranged between 0.12 and
0.68%. The mean concentrations were
0.12, 0.68, 0.53, and 0.49% for products A,
B, C and D, respectively. Previous study
on use of vitamin E and its derivatives in
topical preparations marketed in USA and
Europe revealed that concentrations of the
vitamin ranged between 0.0001% and
more than 20% [6]. Notably, there is a
striking lack of published data on dose-
response studies defining the optimal
dosage of the vitamin E. This could be
certainly due to limited-efficiency control
requirements for non-pharmaceuticals,
such as vitamin E. Furthermore, it may be
attributed to ill-defined study end points
and to the difficulty of measuring
oxidative stress in vitro. The authors
remarked that if the product claim is to
improve antioxidant protection of skin
barrier, topical formulations with vitamin
E at concentrations ranging from 0.1 to 1%
are likely to be effective. Accordingly, the
same authors suggested using vitamin E in
combination with co-antioxidants such as
vitamin C to help enhancing antioxidant
effects and stability of vitamin E [6].
Although the tested commercial products
in the present study pointed out a
concentration range similar to that
suggested by Thiele et al., 2005 [6],
nevertheless these products contain the
acetate ester prodrug rather than the active
free vitamin E.
Table 1: General formula of laboratory formulations containing 0.5% (w/w) of vitamin E or vitamin E
Percent w/w
Stearic acid
White soft paraffin
Soybean oil
Corn oil
Captex SBE (Caprylic/ Capric/Stearic Triglyceride)
Acconon S-35 (PEG-35 SoyGlycerides)
Potassium hydroxide
Stability of Vitamin E/Acetate in
Experimental and Commercial Products
The tested products were subjected to
stability study upon storage at three
different temperature levels; refrigerator
(2-8 C), room temperature (22-25 C) and
elevated temperature at 37 C.
Physical Stability
In product A, the consistency and the color
of the cream stored at 37 ºC was changed.
The cream became thinner and the color
changed from white color to off-white.
Regarding product C, the tube showed
leakage at the sealed end after 5 months at
37 ºC. A loss of the cream through leakage
of the cream and separation of waxy
Nada AH et al., Journal of Global Pharma Technology. 2012; 4(03):1-8
© 2009, JGPT. All Rights Reserved.
material was also observed. The loss of
aqueous phase due to water evaporation
might explain the reported unexpected
increase in the vitamin concentration in the
last two months of storage. For product D,
the samples stored at 37 ºC were no longer
homogenous in appearance after 5 months.
On the other hand, experimental cosmetic
preparations maintained the initial
consistency, homogeneity, color and
Chemical Stability
Storage of the commercial and
experimental formulations at various
storage conditions revealed different
stability profiles after different storage
periods. The results of the initial and
remaining concentrations after different
time intervals reported for the
experimental and commercial formulations
are presented in Figs. 1 & 2 and Figs. 3-6,
Experimental Products
The developed two experimental emulsion
cream formulations containing 0.57 and
0.58%w/w of T or TA, designated as F1
and F2 respectively, served to compare the
stability of T relative to TA. These
experimental products were also used to
compare the stability of TA with that of
TA in commercial products, as well as to
evaluate the extraction efficiency of the
tested methods for extraction of T/TA. The
results of stability study are graphically
represented in Figs. 1 and 2. It appears
from the previous results of the
experimental formulations that the free
tocopherol is more susceptible to
degradation, in comparison with the
acetate ester. The free OH in tocopherol
is more easily oxidized by atmospheric
oxygen, which is protected in case of the
ester form. F1 cream containing T lost
about 80% of the initial concentration after
storage for only 20 weeks at 37 C. On the
other hand, TA containing formulation
(F2) lost only about 10% of the initial
concentration after the same storage period
at 37 C. This may be explained by the
higher sensitivity of T and absence of any
added antioxidant to these formulations.
Avoiding addition of antioxidant was
intended to objectively assess the effect of
formulation on unprotected T/TA in such
preparations upon storage. The
degradation was quite appreciable and
proportional with the increase of the
storage temperature in the order of 37 C >
25 C > 2-8 C (Figs. 1 and 2).
Fig.1a: Stability of Experimental cream F1 at 2-80 C.
Fig.1b: Stability of Experimental cream F1 at 25ºC.
Fig. 1c: Stability of Experimental cream F1 at 37 ºC.
Nada AH et al., Journal of Global Pharma Technology. 2012; 4(03):1-8
© 2009, JGPT. All Rights Reserved.
Commercial Products
Since none of the investigated commercial
products declares the actual content of TA
in a quantitative manner, the values
determined on starting the stability study
were considered as the initial (zero point)
concentration for each product. It is
worthy mentioning at this point that
although product A label shows that it
contains only tocopherol acetate, the
results of analysis revealed the presence of
tocopherol also. In contrast, manufacturer
of product B claims the presence of both
vitamin E and vitamin E acetate under the
ingredients, yet the results of analysis
indicated the presence of the ester form
only. Inclusion of T in this formulation
may be intended as a protective
antioxidant to TA, the last is the main
The initial concentration of the vitamin E
acetate (TA) in the commercial products
ranged between 0.12 and 0.68%. The mean
concentrations were 0.12, 0.68, 0.53, and
0.49% for product A, B, C, and D
respectively. The percent of TA remaining
after different times and storage conditions
are graphically represented in Figs. 3-6.
The dramatic degradation upon storage of
experimental preparation F1 at 37 C (Fig.
1) containing T was not observed with any
of the tested commercial preparations
containing TA. Products A, B and C
retained 88-92% of the initial TA
concentration after storage at 37 C for 7
months. Product D showed the maximum
loss after storage under the same
conditions, wherein the remaining
concentration was found to be 76%. These
findings explain why the manufacturers of
commercial products use basically the
more stable acetate ester TA instead of the
free tocopherol, yet the last is the active
Fig. 2a: Stability of Experimental Cream F2 at 2-8°C.
Fig. 2b: Stability of Experimental Cream F2 at 25°C.
Fig. 2c: Stability of Experimental Cream F2 at 37°C.
Fig. 3: Stability of commercial product (A).
Nada AH et al., Journal of Global Pharma Technology. 2012; 4(03):1-8
© 2009, JGPT. All Rights Reserved.
Effect of Exposure/Container on Vitamin
E stability
Before starting the stability study, samples
from the surface and bulk of commercial
cream packed in open-mouth container,
exemplified by product B, were analyzed.
The results revealed insignificant
difference in TA concentration; namely
0.651 (RSD=2.3%) and 0.678% (RSD=
0.065%) for the surface and bulk of
containers respectively. Similarly, to
assess the effect of oxidative exposure of
the experimental products containing
T/TA to the surrounding environment,
samples from F1 and F2, filled in
frequently opened bulk (simulating
customer use) or single-use containers
stored at 25 ºC, were analyzed and their
contents were significantly indifferent as
verified by Kruskal-Wallis test. After 9
months storage of F1 at 25 ºC, the
remaining concentration of T in the
individual and bulk containers was 57.69
and 49.12% respectively. The
corresponding values for F2 containing
TA were 80.5 and 75.75%, respectively,
after the same storage period. Although no
significant difference was observed
between the two container systems,
however, the rate and extent of
degradation of T was by far higher than
TA. The results indicate that the
commercial product B is exhibiting the
same stability profile, whereas the
experimental formulations showed reduced
stability when stored in bulk containers.
This might be due to increased oxidation
of T and TA on exposure to larger surface
area. The absence of such a phenomenon
in product B might be due to the possible
presence of antioxidants.
Stability of vitamin E and its acetate ester
is questionable during use of cosmetic
products by consumers. Free vitamin E is
much more sensitive to oxidative
degradation, compared to the acetate
derivative. This finding explains why
commercial products include often the
acetate ester, which is inactive prodrug,
instead of the active free vitamin.
Fig. 4: Stability commercial product (B).
Fig. 5: Stability of commercial product (C).
Fig. 6: Stability of commercial product (D).
Storage of vitamin E products at 37°C for
1-2 months results in appreciable loss of
activity. Therefore, care must be
experienced to store such preparation in
controlled room temperature before and
after reaching the end-users.
Nada AH et al., Journal of Global Pharma Technology. 2012; 4(03):1-8
© 2009, JGPT. All Rights Reserved.
Drug control authorities should take care
about packaging storage conditions while
auditing cosmetics’ manufacturers or
distributors. In addition, the cosmetic
manufacturers should recommend storage
of such products at low temperatures,
preferably in a refrigerator.
Further studies to optimize such
formulations are required to improve
vitamin E stability and transdermal
permeation to eventually achieve the
expected therapeutic and cosmetic
This work was supported by Kuwait
University, Research Grant No. [PP01/09].
The authors appreciate the technical
assistance of Dr. F. Bandarkar, Mrs. E.
Abraham, Mr. S. Abraham, Mrs. D. Nabil.
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... Thus, the topical use of vitamin E is adequate for its recognized antioxidant and protective activities, favoring the improvement of the skin barrier due to its lipophilic character and also, effectively avoiding lipid peroxidation by protecting cell membranes from the action of free radicals [103]. Gehring et al. [63] evaluated the hydration capacity of the stratum corneum by the use of vitamin E (5%) in water/ oil and oil/water emulsions, demonstrating moisturizing activity in the stratum corneum, in addition to providing indications that indicate retention of water in the stratum corneum. ...
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Vitamins are part of the antioxidant system of human skin, and are detectable in different layers, so the topical application can be an alternative to maintain the functionality of the system. The capacity of the antioxidant gradient of keratinocytes is associated with attenuation of the action of related free radicals in both esthetics and health. These problems arise from extrinsic aging and are related to the risk of cancer. Vitamin E has been proven to have antioxidant and moisturizing properties in the skin and can protect against the damage of UVB radiation, with emphasis on the reduction of acute erythema and photoaging. The choice for the use of topical vitamin E, compared to the oral is given by the safety as mild irritation and it has potential for multifunctional topical formulations. The purpose of the chapter is to review the topical use of formulations with vitamin E, addressing the development, safe use and evaluation of effectiveness.
... Tokoferol mampu meningkatkan hidrasi stratum korneum, meningkatkan pengikatan air pada kulit, mampu menembus lapisan kulit terdalam serta dapat berperan sebagai antioksidan pada epidermis kulit. Kandungan polifenol seperti flavonoid selain berfungsi sebagai antioksidan juga berperan menurunkan paparan sinar UV (25,27). ...
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Paparan sinar UV secara berlebih dapat menyebabkan imunosupresan, photoaging dan kanker kulit, apabila paparan mengenai lapisan kulit dermis akan menyebabkan kulit menjadi gelap, eritema serta terjadi kerusakan jaringan kolagen. Tabir surya memiliki mekanisme perlindungan secara fisik melalui penghamburan sinar matahari yang masuk ke dalam kulit serta perlindungan mekanik melalui absorbsi sinar UV. Senyawa alami yang berpotensi untuk dikembangkan sebagai kosmetik tabir surya melalui mekanisme antiaging adalah senyawa yang mempunya cincin aromatik seperti gugus fenol. Kandungan labu diketahui memiliki aktivitas antioksidan diantaranya polifenol, karotenoid dan tokoferol. Penelitian ini bertujuan untuk memformulasi krim daging buah labu kuning potensinya sebagai tabir surya melalui pengujian nilai SPF menggunakan metode Spektrofotometri. Evaluasi sediaan krim menunjukkan organoleptis berwarna kuning, berbau manis dan berbentuk semi padat. Krim daging labu kuning memiliki nilai pH yang berkisar antara 5,32 – 6,11, daya sebar 5,04 – 5,31 cm, daya lekat 2,77 – 3,73 detik, viskositas 4480 – 7360 cP, dan uji sentrifugasi krim tidak mengalami perubahan. Penyimpanan selama 14 hari sediaan stabil dan tidak mengalami perubahan yang signifikan berdasarkan paired sample T test. Hasil pengujian aktivitas tabir surya menunjukkan nilai SPF F1, F2 dan F3 berturut – turut sebesar 2,15 ± 0,01, 4,69 ± 0,04 dan 5,78 ± 0,02. Krim dengan konsentrasi ekstrak daging buah labu kuning sebesar 5% dan 10% memiliki proteksi tabir surya kategori sedang.
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Vitamins are bioactive compounds naturally found in many different types of food and required by the human body for many biological functions and enzymatic activities. Due to their antioxidant properties, certain vitamin derivatives have been synthesized for inclusion in many cosmetics, thus leading to an increasing incidence of allergic contact dermatitis (ACD) cases. Therefore, the present review may be helpful to provide an insight into the sensitizing role of at least certain vitamins and may also offer possible patch test alternatives for definitive diagnosis. This study was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) guidelines. Literature search regarding ACD cases to vitamins was performed using the Medline, PubMed, Scopus, EMBASE, and Google Scholar databases from January 1940 up to June 2021. A total of 4494 articles matched the keywords used for the researched. Records removed before screening included 15 duplicate articles and 3429 not eligible articles (e.g., not written in English, studies on animals, not relevant to the topic). A total of 1050 articles underwent the screening phase and 258 were therefore excluded as they were not primary studies. Subsequentially, 792 articles were considered eligible for the review and 688 of them were finally excluded as they did not report the outcome of interest. Therefore, 104 articles were definitely included in the present review. ACD to vitamins is still probably an underestimated issue in cosmetology, as many vitamins are considered “natural” and therefore “safe” ingredients. On the contrary, according to current literature, almost all vitamins contained in topical products are able to induce allergic reactions, with the exception of vitamin B2 and vitamin B9. Patch tests are not standardized, thus leading to difficulties in diagnosis.
Background In the summer of 2019, e-cigarette, or vaping, product use-associated lung injury (EVALI) was detected in the United States. Multiple agencies reported illicit tetrahydrocannabinol (THC)-containing e-cigarette, or vaping, products containing vitamin E acetate (VEA) as a substance of concern. Methods As an expansion of the Utah Department of Health's response to EVALI, the Utah Public Health Laboratory and the Utah Department of Public Safety screened 170 products from 96 seizures between October 2018 and January 2020. Using Pearson's correlation coefficient, we analyzed the temporal correlation of national, and Utah specific case counts, and the percentage of seizures indicating VEA by month. Results The findings indicate strong and significant correlations between seizures indicating VEA and both the national (r = 0.70, p = 0.002) and Utah specific (r = 0.78, p < 0.001) case counts. Conclusion These findings underscore that VEA should not be added to e-cigarettes, or vaping, products and the importance of collaboration with law enforcement when responding to outbreaks associated with illicit substances.
Objective: The main scope of present investigation was preparation and Physicochemical characterization of solid lipid nanoparticles (SLNs) loaded by α-Tocopherol acetate (ATA). Methods: ATA-loaded nanoparticles were prepared by solvent injection-homogenization technique using stearic acid as the solid lipid, phosphatidylcholine as the stabilizer and finally coated by chitosan with the aim of increasing z-potential and also having a more stable nano-formulation. Then, characterization of SLNs has been conducted using dynamic light scattering (DLS), zeta potential measurement, fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC). Results: Nanoparticles with average sizes of 175 ± 15 nm and zeta potential of +35 ± 2.5 mV were obtained. An excellent drug entrapment efficiency of 90.58 ± 1.38% was obtained with a no-burst slow release up to about 10 days tested. The final plateau of release of alpha tocopherol acetate from nanoparticulate system within 216 hours was 61.13 ± 0.13% which was approached in about 150 hrs. Physical stability studies showed that the ATA nano-formulation remained stable with slight increase in mean particle size and polydispersity index over a 3-month period in refrigerated temperature. Considering both FTIR and DSC analysis, it can be concluded that there is no new band formation between materials and ATA in our nano-formulation. Particle sizes obtained using AFM images are in a good agreement to those established from the DLS analysis. Conclusion: These data showed a promising delivery system for vitamin E based on SLN platform.
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A specific HPLC method, with an RP-C-18 column and a UV detector, for simultaneous determination of vitamin E (tochopherol, T)/T acetate (TA) in four commercial and two experimental cosmetic products is described. Three solvent systems for extraction of T/TA were assessed: isopropyl alcohol; 10:90 v/v hexane-methanol mixture (method 1); and methanol alone (method 2). The procedure was accurate, as indicated by high recovery (97.8-101.8% and 100.1-102.5% for T and TA, respectively) and precise (RSD was only 0.9-3.26% and 0.73-3.35% for T and TA, respectively). The limits of detection for T and TA were 200 and 300 ng/ml, respectively, while the limits of quantitation were 250 and 400 ng/ml, respectively. The range of reliable quantification was 5-50 μg/ml. Isopropanol as solvent resulted in a turbid extract. Method 1 and method 2 of extraction showed high recovery (98.5-99.9% and 97.2-97.9% for T and TA, respectively). After a few weeks of analysis, method 1 resulted in retention time drift, peak broadening, non-reproducible results, and progressive loss of HPLC-column integrity. Methanol alone (method 2) was equally as efficient as that of the mixture of methanol with 10% hexane (method 1) for extraction. The described analytical procedure proved to be accurate, precise, and suitable for simultaneous determination of T and TA in real commercial cosmetic products.
We measured enzymic and non-enzymic antioxidants in human epidermis and dermis from six healthy volunteers undergoing surgical procedures. Epidermis was separated from dermis by currettage and antioxidants were measured by high-performance liquid chromatography (HPLC) or standard spectrophotometric methods. The concentration of every antioxidant (referenced to skin wet weight) was higher in the epidermis than in the dermis. Among the enzymic antioxidants, the activities of superoxide dismutase, glutathione peroxidase, and glutathione reductase were higher in the epidermis compared to the dermis by 126, 61 and 215%, respectively. Catalase activity in particular was much higher (720%) in the epidermis. Glucose-6-phosphate dehydrogenase and isocitrate dehydrogenase, which provide reduced nicotinamide adenine dinucleotide phosphate (NADPH), also showed higher activity in the epidermis than the dermis by 111% and 313%, respectively. Among the lipophilic antioxidants, the concentration of α-tocopherol was higher in the epidermis than the dermis by 90%. The concentration of ubiquinol 10 was especially higher in the epidermis, by 900%. Among the hydrophilic antioxidants, concentrations of ascorbic acid and uric acid were also higher in the epidermis than in the dermis by 425 and 488%, respectively. Reduced glutathione and total glutathione were higher in the epidermis than in the dermis by 513 and 471%. Thus the antioxidant capacity of the human epidermis is far greater than that of dermis. As the epidermis composes the outermost 10% of the skin and acts as the initial barrier to oxidant assault, it is perhaps not surprising that it has higher levels of antioxidants.
Ultraviolet (UV) irradiation of C3H/HeN mice induces skin cancer and an immunosuppression that prevents the host from rejecting antigenic UV-induced tumors. The capacity of topical vitamin E (dl-alpha-tocopherol) to prevent photocarcinogenesis or the immunosuppression induced by UV irradiation were assessed. Skin cancer incidence in UV-irradiated mice was 81% at 33 weeks after the first UV exposure; application to mice of 25 mg vitamin E three times per week for three weeks before UV irradiation, and throughout the experiment, reduced this incidence to 42% (p = 0.0065, log rank test). Immunoenhancement by vitamin E was assessed by comparing levels of immunosuppression by splenocytes from normal or UV-irradiated mice, with and without topical vitamin E treatment. Transfer of splenocytes from UV-irradiated mice to naive mice prevented the recipients from rejecting a UV-induced tumor challenge, whereas splenocytes from UV-irradiated mice treated with vitamin E did not prevent recipients from rejecting a similar tumor challenge. Phenotypic analysis of splenocytes used in the passive transfer assay, conducted with a biotin-avidin-immunoperoxidase technique, revealed that vitamin E treatment of mice undergoing UV irradiation prevented the UV-induced down regulation of Ia expression in splenocytes and increased the proportion of Lyt-2+ and L3T4+ splenocytes. Therefore, chronically applied vitamin E can effectively reduce cancer formation and immunosuppression induced by UV irradiation. Prevention of UV-induced down regulation of Ia expression may have contributed to this immunomodulation.
Albino hairless mice (Skh:HR-1) exposed chronically to suberythemal doses of ultraviolet radiation develop visible skin changes, histological alterations, and tumors. Topical treatment of mice with solutions of superoxide-scavenging antioxidants (such as alpha-tocopherol, ascorbic acid, propyl gallate and Trolox) prior to each UVB radiation exposure reduced significantly the severity of these events. Tocopherol esters and ascorbyl palmitate were not as effective as the parent compounds in providing protection. The data suggest a role for superoxide in UVB radiation-induced skin photoaging and the protective potential of superoxide scavengers. In contrast, the severity of UVA radiation-induced mouse skin damage was not reduced by topical application of the antioxidants tested here.
The generation of free oxygen radicals is believed to play an important pathogenic role in the development of various disorders. More than other tissues, the skin is exposed to numerous environmental chemical and physical agents such as ultraviolet light causing oxidative stress. In the skin this results in several short- and long-term adverse effects such as erythema, edema, skin thickening, wrinkling, and an increased incidence of skin cancer or precursor lesions. However, accelerated cutaneous aging under the influence of ultraviolet light, usually termed photoaging, is only one of the harmful effects of continual oxygen radical production in the skin. Others include cutaneous inflammation, autoimmunological processes, keratinization disturbances, and vasculitis. Vitamin E is the major naturally occurring lipid-soluble non-enzymatic antioxidant protecting skin from the adverse effects of oxidative stress including photoaging. Its chemistry and its physiological function as a major antioxidative and anti-inflammatory agent, in particular with respect to its photoprotective, antiphotoaging properties, are described by summarizing animal studies, in vivo tests on human skin and biochemical in vitro investigations. The possible therapeutic use in different cutaneous disorders, and pharmacological and toxicological aspects are discussed. Many studies document that vitamin E occupies a central position as a highly efficient antioxidant, thereby providing possibilities to decrease the frequency and severity of pathological events in the skin. For this purpose increased efforts in developing appropriate systemic and local pharmacological preparations of vitamin E are required.
Considerable interest has been recently generated concerning the use of natural compounds, anti-oxidants in particular, in photoprotection. Two of the best known anti-oxidants are vitamins C and E, both of which have been shown to be somewhat effective in different models of photodamage. Very little has been reported, however, on the effectiveness of a combination of the two (known to be biologically the more relevant situation); nor have there been detailed studies on the ability of these antioxidants to augment commercial sunscreen protection against UV damage. We report that (in swine skin) vitamin C is capable of additive protection against acute UVB damage (sunburn cell formation) when combined with a UVB sunscreen. A combination of both vitamins E and C provided very good protection from a UVB insult, the bulk of the protection attributable to vitamin E. However, vitamin C is significantly better than vitamin E at protecting against a UVA-mediated phototoxic insult in this animal model, while the combination is only slightly more effective than vitamin C alone. When vitamin C or a combination of vitamin C and E is formulated with a commercial UVA sunscreen (oxybenzone), an apparently greater than additive protection is noted against the phototoxic damage. These results confirm the utility of anti-oxidants as photoprotectants but suggest the importance of combining the compounds with known sunscreens to maximize photoprotection.
Skin cancers are a serious health problem in the United States. One common method of skin cancer primary prevention is use of sunscreens. Research has been conducted to ascertain the role of active ingredients of sunscreen products in photoprotection and possible carcinogenesis. In contrast, little is known about the "other ingredients", listed or unlisted, on sunscreen product labels. One such ingredient is vitamin E. usually in the form of alpha-tocopherol acetate. Results of recent studies of skin carcinogenesis in an ultraviolet (UV) B mouse carcinogenesis model suggest that topically applied alpha-tocopherol acetate does not prevent and, under some conditions, enhances skin cancer development and growth, whereas the free unesterified from of alpha-tocopherol significantly reduces experimental UVB carcinogenesis. We have performed a Phase II cancer prevention study to evaluate whether topically applied alpha-tocopherol acetate is absorbed in human skin and metabolizes to the free or other forms. In this double-blind study, 19 men and women > 30 years of age who had at least three actinic keratoses on their forearms were randomly assigned to apply alpha-tocopherol acetate (125 mg/g) or difluoromethylornithine cream to their arms twice daily for three months. Blood samples and photographs and punch biopsies of actinic keratoses were obtained before and at the end of the study (Month 4). Plasma and skin concentrations of free alpha-tocopherol, alpha-tocopherol acetate, and gamma-tocopherol were analyzed by high-performance liquid chromatography at Month 4. The results of this report focus only on data obtained from the 11 participants randomized to the alpha-tocopherol acetate arm of the study. Topically applied alpha-tocopherol acetate was substantially absorbed in skin, with no evidence of conversion within skin to its unesterified form (i.e., free alpha-tocopherol). There was no evidence of systemic availability or biotransformation of topically applied alpha-tocopherol acetate. In summary, we have determined that alpha-tocopherol acetate is not metabolized to the free form of alpha-tocopherol in plasma or skin.
Background: Chronologically aged skin exhibits delayed recovery rates after defined barrier insults, with decreased epidermal lipid synthesis, and particularly a reduction in cholesterol synthesis. Prior studies in young mice (< 10 weeks) and humans (20 to 30 years of age) have shown that application of a mixture of cholesterol, ceramides, and essential/nonessential free fatty acids (FFAs) in an equimolar ratio allows normal barrier recovery, whereas any 3:1:1:1 ratio of these four ingredients accelerates barrier recovery. Objective and methods: Our purpose was to compare the ability of equimolar and cholesterol- and FFA-dominant molar lipid mixtures (2% in propylene glycol/n-propanol, 7:3) versus vehicle alone on barrier recovery rates at 0, 3, 6, 24, 48 hours, and 1 week after tape stripping of aged hairless mouse (> 18 months) and chronologically aged human skin (80 +/- 5 years). Results: Whereas a single topical application of the equimolar mixture only allows normal recovery in young mice, it appeared to improve barrier recovery in chronologically aged mice (p < 0.06). Moreover, a 3:1:1:1 mixture with cholesterol as the dominant lipid further accelerated barrier recovery at 3 and 6 hours (p < 0.01 and p < 0.03, respectively, vs 1:1:1:1). Likewise, the cholesterol-dominant, optimal molar ratio mixture significantly accelerated barrier recovery in chronologically aged human skin at 6 hours (p < 0.005; n = 6). In contrast, in aged mice, an FFA-dominant mixture significantly delayed barrier recovery at 3, 6, and 24 hours (p < 0.005, 0.05, and 0.001, respectively), Finally, ultrastructural studies showed that lipid-induced, accelerated recovery in chronologically aged mice is associated with the accelerated replenishment of the stratum corneum interstices with lamellar unit structures. Conclusion: These findings show that barrier recovery is accelerated in chronologically aged murine epidermis with optimized ratios of physiologic lipids, provided that cholesterol is the dominant lipid and that the same mixture also accelerates barrier recovery in chronologically aged human skin.
The influence of vitamin E (tocopherol, CAS 10191-41-0) on stratum corneum hydration was tested in O/W and W/O emulsions. Additionally, the O/W emulsion was used in an in vivo/in vitro method to gravimetrically obtain evidence concerning the water-binding capacity of the stratum corneum. In the W/O emulsion, 2.5%, 5%, and 7.5% vitamin E were compared. With both types of emulsions, vitamin E increased the stratum corneum hydration statistically significantly (p = 0.0002). In addition, we could provide evidence of an enhanced water-binding capacity after treatment with vitamin E (p = 0.05). For the hydrating effect of vitamin E. its concentration is of importance. The optimum concentration turned out to be 5%.