Accepted Article
Retinoids stability and degradation kinetics in commercial cosmetic
products
Žane Temova Rakuša, Petja Škufca, Albin Kristl, Robert Roškar*
University of Ljubljana, Faculty of Pharmacy, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia
E-mail addresses:
Ž. Temova Rakuša – zane.temova.rakusa@ffa.uni-lj.si
P. Škufca - petja.skufca@gmail.com
A. Kristl - albin.kristl@ffa.uni-lj.si
*Corresponding author: robert.roskar@ffa.uni-lj.si
Tel: +386 1 4769 500, Fax: +386 1 4258 031.
Funding: This research was financially supported by the Slovenian Research Agency (ARRS)
[P1-0189].
Data availability statement: Data available on request from the authors.
This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process, which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1111/jocd.13852
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DR. ŽANE TEMOVA RAKUŠA (Orcid ID : 0000-0001-8948-9129)
Article type
: Original Contribution
Title: Retinoids stability and degradation kinetics in commercial cosmetic products
Running head: Retinoids stability and degradation kinetics
Abstract
Background: Retinoids as dermatological agents are effective against acne, psoriasis, skin-
aging, and other skin conditions. However, their susceptibility to degradation is a limiting
factor for their wide-spread use.
Objectives: Within this study, we aimed to provide comprehensive and evidence-based
information on retinoids stability and degradation kinetics in commercial cosmetics, focusing
on different factors affecting their stability.
Methods: A validated HPLC-UV methodology was utilized for determination of the most
common retinoids in cosmetics (retinol, retinyl palmitate, β carotene) and a newer promising
retinoid (hydroxypinacolone retinoate). The stability of 16 retinoid derivatives in 12
commercial cosmetics was evaluated within 6 months of long-term and accelerated stability
testing in addition to a one-week photostability study. Retinoid degradation in the tested
formulations followed first-order kinetics, which was further applied to shelf-lives prediction.
Results: Long-term and accelerated stability testing revealed retinoid instabilities in almost
all products, resulting in a 0-80% decline after 6 months at 25 °C and a 40-100% decline at
40 °C, which were kinetically evaluated. Light degradation was more pronounced than
temperature-induced degradation. Among the studied retinoids, the stability of the newer
hydroxypinacolone retinoate was the most prominent. This study also identifies correlations
between retinoid concentrations, price, formulation, and their stability in cosmetics.
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Conclusions: Retinoid instabilities were formulation depended and associated with lower
contents than declared in some cosmetics. Retinoid chemical and physical stability in topical
formulations need to be evaluated by real-time stability studies, instead of the more
frequently used accelerated stability studies.
Keywords: cosmeceutical, cosmetic formulation, cosmetics, retinoids, stability, vitamin A
1. Introduction
The term retinoid refers to retinol and its analogues as well as carotenoids with vitamin A
activity (beta carotene). In addition to the many different functions in the human body,
retinoids also have various beneficial effects on the skin. Topical retinoids are effective in the
treatment of acne, psoriasis, hyperpigmentation, photoaged or intrinsically aged skin, and
dyschromia and are thus utilized in cosmetology and dermatology.1 However, two main
issues are limiting the wide-spread use of topical retinoids: application site irritation (itching
or burning sensation, erythema, dryness, peeling, photosensitivity)2 and their instability in
cosmetic and pharmaceutical products. The latter is also addressed by the Scientific
Committee on Consumer Safety (SCCS), Secretariat at the European Commission,
Directorate General for Health and Food Safety, within the SCCS Opinion on vitamin A
(retinol, retinyl acetate, retinyl palmitate), which emphasizes the lack of stability data of
vitamin A in different product formulations and the need of proper stabilization through final
formulations.3
Several studies in the literature have evaluated the stability of selected retinoids in
pharmaceuticals,4,5 simple solutions,6,7 parenteral nutrition solutions,8–10 experimental
cosmetic formulations,7,11–16 as well as commercial cosmetics.17–19 The main conclusions,
which can be drawn by these studies, are as follows: the stability of retinoids depends on the
medium, the pH value, and the presence of other antioxidants,13,14 and is also affected by
environmental storage conditions, since retinoids are liable to light, heat, and oxidation
exposure. Retinyl palmitate is the preferred retinoid in dermatological formulations due to
higher thermal stability than retinol.7 However, a study on its photodecomposition in
cosmetic creams demonstrated that its photoirradiation can result in the formation of toxic
products associated with photocarcinogenesis.15 The instability of retinyl palmitate was also
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found to affect the formulation physical integrity.12 The stability of retinyl palmitate can be
significantly improved by the presence of vitamin C and E,11 butylated hydroxytoluene, and
UV filters.20 The published studies thus far on retinoids stability in topical preparation focus
on a selected retinoid, typically retinol or/and retinyl palmitate, whereas the stability of a
wider range of retinoids, often found in such preparations, such as β carotene and
hydroxypinacolone retinoate (HPR), has not yet been described. Furthermore, the effect of
storage conditions on retinoids, frequently present in commercial cosmetics has not yet been
systematically and kinetically evaluated. Within this article, we present a comprehensive
study on the stability of vitamin A derivatives in several topical products, including longterm, accelerated, and photostability testing, as well as evaluation of degradation kinetics, the
applicability of accelerated testing to shelf-life determination, and associations between
different factors affecting their stability.
2. Materials and methods
2.1. Chemicals and reagents
All following materials: all-trans-retinol (≥99%), all-trans-retinyl palmitate (≥ 99%), β
carotene (≥99%), butylated hydroxytoluene (BHT), as well as HPLC grade acetonitrile,
methanol, n-hexane, and tetrahydrofuran were purchased from Sigma-Aldrich (Steinheim,
Germany). Retinyl acetate (≥97 %) was purchased from Carbosynth (Berkshire, UK). Ultrapure water was obtained through a Milli-Q water purification system A10 Advantage
(Millipore Corporation, Bedford, MA, USA).
2.2. Commercial cosmetic products
12 cosmetic products, including both products with declared retinoid content as well as
products with listed retinoids as ingredients, were purchased in Slovenia in May 2019. These
included products in various price ranges and formulations: day creams (Afrodita, Eveline,
Eucerin, Green Line, L'oreal, Lekarna Ljubljana, Paula's Choice), day cream for men
(Ombia), and serums (2×The Ordinary, Paula's Choice, and Revolution).
2.3. HPLC-UV analysis
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Retinoid contents in the tested commercial cosmetic products at each time point were
measured by a validated HPLC-UV method21 using an Agilent 1100/1200 Series instrument
(Agilent Technologies, Santa Clara, California, USA) equipped with a UV-VIS detector and
ChemStation data acquisition system. In brief, the chromatographic separation was performed
on a reversed-phase column Luna C18 (2) 150 × 4.6 mm, 3 μm particle size (Phenomenex,
Torrance, CA, USA) at 40 °C. Mobile phase, consisting of water (A), acetonitrile (B) and
acetonitrile: tetrahydrofuran (50:50, v/v) (C) in gradient elution mode was utilized as follows:
(time (min); % A; % B): (0; 10; 5), (4; 5; 5), (8; 5; 5), (8.1; 10; 5) at a flow rate of 1 mL/min.
Retinoids were monitored at characteristic wavelengths: 325 nm, except for β carotene (450
nm). Injection volume was between 10 and 40 μL, according to the retinoid amounts in the
tested products.
2.4. Sample preparation
Samples for retinoid quantification in at least triplicate were prepared following the validated
method.21 The sample preparation procedure was adjusted to retinoid contents after
preliminary testing of each cosmetic product.
In brief, the samples for retinoid quantification in semi-solid cosmetic products were
prepared by weighing a predefined amount (75-1,000 mg) of the cream into a plastic tube,
followed by the addition of mobile phase B (2 mL) and sonication (5 min). Hereafter, 8 mL
of n-hexane with BHT (500 mg/L) was added to the samples, followed by vortex mixing (5
min) and centrifugation (4,130×g, 25 ºC, 10 min). A part of the supernatant (0.5 - 1.5 mL),
adjusted to retinoid content in the specific cream was evaporated to dryness under a stream of
nitrogen at 40 °C (TurboVap LV, Caliper, Hopkinton-MA, USA). Dry residues were
reconstituted with predetermined volume (0.5 - 2.0 mL) of mobile phase C with BHT (150
mg/L), followed by sonication (10 min), and vortex mixing (1 min). When necessary, the
samples were centrifuged (16,200×g, 25 °C, 5 min) before analysis.
The samples for retinoid quantification in liquid cosmetic products were prepared by diluting
the serum (100-1,000 μL) with mobile phase C with BHT (150 mg/L) up to a predefined
volume (5 - 50 mL), depending on retinoid content. The samples were sonicated (10 min),
filled up to the mark of the volumetric flask with the same solvent, and vortexed (5 min).
When necessary, the samples were centrifuged (16,200×g, 25 °C, 5 min) before analysis.
2.5. Stability study
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The cosmetic products (Section 2.2.) were exposed to long-term, accelerated as well as stress
testing under the influence of UV and daylight. Stability samples at each time point were
prepared and analyzed in triplicates following the procedures described above (Section 2.4.).
2.5.1. Long-term and accelerated stability testing
Long-term and accelerated stability testing was performed following the ICH Q1A (R2)
guidelines.22 Long-term stability testing was conducted on the cosmetic products in their
original packaging under expected storage conditions (25 °C and 60% relative humidity
(RH)). Accelerated stability testing was conducted at 40 °C and 75% RH on predefined
amounts of the cosmetics, which were previously weighed and stored in closed plastic tubes,
protected from light. The samples for both long-term and accelerated stability testing were
stored in climate chambers. The cosmetics stored at 25 °C were occasionally opened to
simulate their real-life usage. The content and appearance of all samples were evaluated
immediately after opening (initial content) as well as at regular time points during 6 months
period: after 1 week, 2 weeks, 1, 2, 3, and 6 months.
2.5.2. Photostability testing
The cosmetic products for stability testing were also exposed to photostability testing
following the ICH Q1B guidelines (ICH Q1B, 1996), option 2 in a climate chamber with a
light module (ICH 260L, Memmert, Büchenbach, Germany). Predefined amounts of the
cosmetics were initially weighted, stored in closed transparent plastic tubes, and analyzed
after 1, 3, and 7 days.
2.5.3. Kinetic studies
Retinoid concentrations were obtained at different time points during the stability testing.
Zero, first and second order of degradation was calculated for each sample. The most
appropriate kinetic order (according to the correlation coefficient) was selected and applied
for the calculation of degradation constant (k) and shelf-life, which was defined as a 10%
decline in concentration (t90%).
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3. Results and discussion
3.1. Stability of retinoids during 6 months of long-term and accelerated
stability testing
Retinoid stability in commercial cosmetic products in various formulations was evaluated
after their opening, during 6 months of storage at room temperature and elevated temperature.
The obtained results showed a significant decline of retinoids practically in all tested products
(Fig. 1). The decline in retinoid contents after 6 months at 25 °C ranged from 0 to 80%. The
decline was greater at higher storage temperature in all samples (40-100% at 40°C), resulting
in total degradation of the retinoids in almost one-third of the tested products. Even in the
most stable formulation, 40% degradation was observed after 6 months at 40 °C (R (F3) in
Fig. 1). No significant difference was observed between the stability of retinol (25-93%
remained) and retinyl palmitate (20-100% remained) after 6 months of storage at 25 °C. The
stability of β carotene was better in both tested formulations at the same storage conditions
(83% remaining). However, because of the smaller sample size and its very low content, we
cannot draw any concrete conclusions.
The stability of the newer retinoid (HPR) was also evaluated, which has not yet been studied
in the accessible literature. Its structure was confirmed by LC-MS before the stability study.21
HPR was found very stable in the tested formulation at 25 °C after 6 months (95% of the
initial content remained). High chemical stability was also evident at 40 °C (97% of the
initial content remained after 3 months). However, physical instability was observed during
the last 3 months of storage at elevated temperature, resulting in a stratification of the
product.
Retinoid concentration in the tested formulations is evidently not the determining factor for
their stability since extensive degradation (around 70%) was observed in both formulations
with the highest retinoid contents (Fig. 1). The most important factor in ensuring their
stability was the formulation itself, which was not guaranteed by the product price. The
formulations with the lowest retinoid degradation (R (F3), R (F5), R (F7), Rpal (F3), and
HPR (F8)) belong to the lower-mid price range (up to 50 € per 50 mL), whereas the tested
highest-priced products were subjected to more extensive degradation.
3.2. Effect of temperature on retinoid degradation kinetics
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Degradation kinetics could offer more in-depth insights into retinoid instability in topical
formulations but are only rarely utilized within stability evaluation in cosmetic formulations.
We assessed this issue by initial determination of the best model to describe the degradation
kinetics of retinoids. Therefore, zero, first, and second-order models were tested. The
decrease in retinoid concentration followed first-order kinetics in most products (R2 > 0.99,
Table 1), which is in agreement with previous reports on retinol24 and retinyl palmitate.12
Shelf-lives, defined as 90% of the initial retinoid concentration, were also calculated for each
tested cosmetic product at both temperatures (Table 1). The newest generation retinoid (HPR)
was the most stable retinoid among the tested formulation at ambient temperature, with more
than two-fold longer shelf-life compared to the second most stable retinoid (Rpal (F3)).
Excluding the new retinoid (HPR), which significantly deviates from the others, the average
shelf-life at 25 °C was about 2 months; in one-third of the tested cosmetics, it was < 1 month.
Although the actual stability in sealed packaging may be better, the obtained shelf-lives are
much shorter than the generally declared 6-months or 12-months shelf-lives after opening.
At elevated temperature (40 °C), the shelf-lives were significantly shortened to an average of
< 14 days. The effect of the temperature on retinoid stability can most readily be observed
from the ratio of rate constants k40°C and k25°C (Table 1). The increase in temperature did not
affect the stability of retinoids in some formulations (F11 and F6 in Table 1), while
significantly accelerating the degradation of others (up to 80-fold for Rpal in F2). On
average, 15 °C higher storage temperature increased the reaction rate constants by a 5.2-fold
(excluding Rpal (F2), which deviated significantly from the rest), but considering the vast
differences (1.0-78.7), it can be concluded that the thermal stability of the cosmetic products
is formulation dependent. Since higher temperature increased the retinoid degradation rates to
a very different extent, the results of the accelerated tests allow only limited extrapolation to
ambient temperature. In cases when elevated temperature caused physical changes (2 cases in
our study, Section 3.3.) accelerated stability studies were not predictive of their long-term
chemical stability or their shelf life. Therefore, stability information needs to be obtained
from real-time stability studies, even though the faster accelerated stability testing is usually
performed in the cosmetic industry, to predict the stability of the cosmetic product.12
Accelerated stability studies can however be useful in showing the impact of short-term
deviations from the stated storage conditions, which might occur during transport or storage.
3.3. The cosmetics appearance during storage
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All tested cosmetics were also evaluated for changes in appearance during six months of
stability study at both storage conditions. Macroscopic separation was observed in two of the
12 tested products. Phase separation was observed in one liquid dosage form (o/w emulsion),
which did not occur before three months of storage at 40 °C, while no change was observed
at 25 °C. Phase separation was also observed in one semisolid dosage form, where the oil
phase had visibly accumulated on the surface of the cream after one month of storage.
3.4. Retinoid contents at shelf-lives
Degradation kinetics (Section 3.2.) was applied to determine the remaining retinoid contents
at the shelf-lives of the tested cosmetics, as determined and declared by their manufacturers.
For such purposes, stability data at ambient temperature, simulating their real-life usage, was
utilized. Most cosmetics declared a 6-months or 12-months shelf-life after opening. Less than
one-third of the tested cosmetics contained ≥80% of the initial retinoid content at their shelflives, while more than half of them contained about or less than half of the retinoid contents
(Table 2). The predicted retinoid contents after 6 months of storage were comparable with the
determined retinoid contents within the stability study (Table 2), thus demonstrating the
applicability of the employed concept for shelf-lives prediction.
3.5. Relation between retinoid concentrations and their stability
The effect of retinoid contents on their stability was also assessed in the tested cosmetics.
Higher found concentrations did not have a stabilizing effect on the retinoids, although in
some of the tested products inversely proportional concentration dependence can be observed
(Fig. 2). Interestingly, retinoids present at higher concentrations seem to be more susceptible
to degradation. As no evident correlation between retinoid concentrations and their rate
constants implied that their stability is formulation dependent, rather than concentrationdependent.
3.6. Relation between the product price and retinoid stability
In the further assessment of factors affecting retinoid stability, the financial aspect was also
included. The considered prices are the retail prices of the commercial cosmetics, purchased
in May 2019, calculated to a uniform volume (50 mL). The results for retinoid stability
(expressed with their first-order reaction rate constant) in relation to the price of the tested
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products are shown in Fig. 3. As can be seen, the cosmetic product with the highest retinoid
degradation rate is the least expensive among the tested cosmetics. However, it is also
evident, that the two most expensive cosmetics, which specifically highlight their high
retinoid contents, do not provide adequate stability within their formulations. Among the
more affordable cosmetics (≤ 20€) the reaction rate constants are very diverse. The cosmetic
product with the lowest reaction rate constant also belongs to this price range. It can be
concluded that the proper formulation of the cosmetics in terms of the active compounds
stabilization is not guaranteed by the price of the product.
3.7. Effect of the formulation on retinoid degradation kinetics
The tested cosmetics were in liquid (serums) or semisolid dosage forms (creams). In general,
retinoids are unstable in water-based liquid preparations. However, this was not observed in
our study as the most stable retinoid (HPR) was formulated in liquid dosage form (F8 - o/w
emulsion). In the remaining two liquid formulations, where retinoids were dissolved in
various oils, their stability was comparable to that in semisolid dosage forms and was most
likely associated with the type and quality of the oil (especially peroxide content) as well as
the added excipients.25 No pattern was observed in retinoid degradation rates in different
dosage forms (Table 3).
Almost all cosmetics involved in the stability study contained some stabilizers, including
antioxidants (e.g. BHT, vitamin C, E) and chelating agents (e.g. EDTA, citric acid), listed in
Table 3 in the same order as on the ingredient list. Vitamin E derivate - tocopheryl acetate is
also listed because some products state its antioxidant activity. However, it acts as an
antioxidant only after its hydrolysis in the skin but does not have a stabilizing (antioxidant)
effect during the storage of the formulations.26 The stabilizing effect of other listed stabilizers
on retinoids has already been established.4,7,20 However, retinyl palmitate was the least stable
in the formulation with the largest number of added stabilizers, whilst the most stable retinoid
formulation contained only one stabilizer (EDTA). Therefore, it can be concluded that the
presence of various stabilizers does not assure the stability of retinoids in cosmetic products.
Their stability in formulations is more likely dependent on the amount of added stabilizer
then on the presence of different stabilizers or their larger number. Since manufacturers do
not provide information on the contents of the added stabilizers, this thesis cannot be
confirmed and would require further studies.
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3.8. Photostability evaluation
Photostability testing was performed following the ICH Q1B guidelines23 to evaluate retinoid
photosensitivity in the tested products. All tested retinoids were found overall photosensitive
with degradation rates dependent on the formulation. Retinol remained at highest amounts
(64-90% of the initial content) in three out of four tested semi-solid products; however, it
degraded completely in the remaining two liquid products. Retinyl palmitate and β carotene
were found more liable to photodegradation, resulting in almost complete degradation in all
of the tested semi-solid products (Fig. 4), which is in accordance with the literature data.7
Contrary to stability results at elevated temperature, exposure to light also significantly
affected the newer retinoid (HPR), resulting in a 40% decrease after one week. On average,
only 20% of the initial retinoid content remained after one week of light exposure, ranging
from the total (100%) to a 10% decline of retinoids. When comparing different retinoids after
the same exposure time to a single factor of instability (elevated temperature and light
exposure), light degradation was substantially more pronounced than temperature-induced
degradation (Fig. 4). To achieve adequate photostability, the addition of UV filters to the
cosmetics should be considered, which were not listed in any of the daycare products,
subjected to the stability study.
3.9. Effect of retinoid stability on their content
The obtained results for degradation kinetics during long-term and accelerated stability
testing also provided certain explanations to the observed deviations between the declared
and found retinoids in the five tested cosmetics with declared retinoid content. The greatest
deviation from the declared content (0.3% retinol), was observed in one of the tested serums
(F2), where retinol was not found (below LOQ – 6.2 nanograms per gram of cosmetic
product). In this product, we evaluated the stability of the found retinoid – retinyl palmitate
(marked Rpal (F2) in Table 1). Considering its high degradation rate (t90% < 15 days at room
temperature) and the most significant temperature effect on its degradation, it is evident, that
this formulation does not provide adequate chemical stability of retinoids. The stability
testing of the cosmetic product, which contained half of the declared retinol (53.7 ± 1.5 %),
revealed that in this formulation retinol had the highest degradation rate at room temperature
(R (F4) in Table 1). Its inadequate stabilization through this formulation is evident.
Significantly lower content was also determined for HPR in F8 (5.3 ± 2.0 %), for which
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stability was not an issue. HPR was the most stable retinoid with a shelf-life of about one
year. Since HPR commercial standard was not available, its quantification was based on its
structurally most similar retinoid - retinyl acetate. Therefore, slight deviations are possible,
which, however, are not the reason for such low content. In the remaining two cosmetic
products with specified retinoid contents, higher contents than declared were detected: R (F1)
- (131.8 ± 2.2 %), and R (F5) - (128.5 ± 3.3 %).
4. Conclusions
Retinoids as dermatologic agents are effective in the treatment of acne, psoriasis, photoaged
and intrinsically aged skin as well as other skin diseases. However, they require proper
stabilization through their final cosmetic or pharmaceutical formulations. In this paper, we
evaluated the stability of the most commonly used retinoids in commercial cosmetics in
various formulations. Long-term and accelerated stability testing revealed retinoid
instabilities in almost all tested commercial cosmetics, which were formulation dependent,
wherein not dependent on the retinoid concentration nor the product price. Within
photostability evaluation of the products, all tested retinoids were found overall
photosensitive, among which retinol was found the most stable. Retinoid degradation in the
tested formulations followed first-order kinetics, which was further applied to shelf-lives
prediction. Accelerated studies were found not suitable for the prediction of the quantitative
chemical stability of tested products. Most cosmetics declared a 6-months or 12-months
shelf-life after opening and less than one-third of the tested cosmetics contained ≥80% of the
initial retinoid content at their shelf-lives, while half of them contained about half of the
retinoid contents. Based on the obtained results after long-term and accelerated stability
studies, it is evident that lower retinoid contents in some of the commercial products, which
specifically defined their retinoid contents, are a consequence of their instability. Such
stability evaluation would offer more in-depth information as well as general conclusions if
manufacturers would provide the missing information on the manufacturing date as well as
retinoid contents.
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Beijersbergen van Henegouwen GMJ, Junginger HE, de Vries H. Hydrolysis of RRRα-tocopheryl acetate (vitamin E acetate) in the skin and its UV protecting activity (an
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in vivo study with the rat). J Photochem Photobiol B Biol 1995;29:45–51.
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Table 1. Effect of temperature on the degradation kinetics of retinoids in commercial
cosmetics.
25 °C
-1
2
40 °C
-1
Ratio
2
k (month )
R
t90% (days)
k (month )
R
t90%
k40°C/k25°C
Rpal (F6)
0.277
1.000
11.6
0.317
0.995
10.1
1.1
R (F4)
0.234
0.973
13.7
1.990
1.000
1.6
8.5
Rpal (F2)
0.218
0.996
14.7
17.15
1.000
0.2
78.7
R (F1)
0.202
0.999
15.9
2.446
0.996
1.3
12.1
Rpal (F11)
0.160
0.928
20.0
0.164
0.997
19.5
1.0
R (F11)
0.150
0.894
21.4
0.292
0.996
11
1.9
βcar (F11)
0.138
0.959
23.2
0.133
0.992
24.1
1.0
Rpal (F9)
0.076
0.998
42.1
0.425
0.993
7.5
5.6
R (F3)
0.048
0.914
67.1
0.079
0.999
40.4
1.7
R (F5)
0.047
0.945
68.7
0.641
0.996
5.0
13.8
Rpal (F10)
0.042
0.999
76.0
0.133
0.998
24.1
3.2
βcar (F12)
0.032
1.000
98.7
0.145
0.996
22.1
4.5
R (F7)
0.024
1.000
133
0.150
0.996
21.4
6.2
Rpal (F3)
0.018
1.000
174
0.193
0.995
16.6
10.5
HPR
0.008
0.998
384
0.017*
0.992
188
2.0
Rpal (F4)
nd
nd
nd
0.623
0.975
5.1
nd
*stable for 3 months (97%), afterward physical changes (stratification) occurred.
nd – not determined because of its stability (no degradation).
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Table 2. Retinoid contents in tested commercial cosmetics at their shelf-lives.
Retinoid
Declared shelf-life after
Predicted retinoid
Determined retinoid at
(Formulation)
opening (months)
remaining at shelf-life (%)
shelf-life (%)
Rpal (F6)
12
3.6
19.0*
Rpal (F2)
12
7.0
26.2*
βcar (F11)
defined expiration date
10.6
46.0*
R (F11)
defined expiration date
11.0
17.4*
Rpal (F11)
defined expiration date
12.9
38.4*
R (F4)
6
26.3
24.6
R (F1)
6
29.7
30.0
Rpal (F9)
12
40.4
63.5*
R (F5)
12
56.2
84.6*
βcar (F12)
12
68.1
82.3*
R (F3)
6
73.1
78.1
R (F7)
6
86.6
88.7
Rpal (F3)
6
89.8
89.6
Rpal (F10)
defined expiration date
92.2
77.7*
HPR (F8)
6
95.4
95.2
*retinoid content was not determined, in the case of shelf-life longer than 6 months and therefore determined
retinoid (%) after 6 months is presented.
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Table 3. Effect of the presence of antioxidants and stabilizers on the degradation kinetics of
retinoids in tested commercial cosmetics.
k25 °C (month-1)
Dosage
form
Stabilizers in the cosmetics
Tocopheryl Acetate, Tocopherol, Ascorbyl Palmitate, Ascorbic
Rpal (F6)
0.277
Semisolid
R (F4)
0.234
Semisolid
Tetrahexyldecyl Ascorbate, Tocopheryl Acetate, Disodium EDTA
Rpal (F2)
0.218
Semisolid
Tocopheryl Acetate, Tetrahexyldecyl Ascorbate
R (F1)
0.202
Liquid
BHT
Rpal (F11)
0.160
R (F11)
0.150
Semisolid
Tocopheryl Acetate, Citric Acid, Beta-Carotene, Tocopherol
βcar (F11)
0.138
Rpal (F9)
0.076
Semisolid
Disodium EDTA, Tocopherol
R (F3)
0.048
Semisolid
R (F5)
0.047
Liquid
BHT, BHA
Rpal (F10)
0.042
Semisolid
Tocopherol, Citric acid
βcar (F12)
0.032
Semisolid
R (F7)
0.024
Semisolid
Rpal (F3)
0.018
Semisolid
HPR (F8)
0.008
Liquid
acid, Citric acid, BHT
Tocopheryl Acetate, Ascorbic Acid, Sodium Ascorbyl Phosphate,
Disodium EDTA, BHT
Tocopheryl Acetate, Sodium Ascorbyl Phosphate, Trisodium
EDTA, Tocopherol
Tocopherol, Disodium EDTA
Tocopheryl Acetate, Ascorbic Acid, Sodium Ascorbyl Phosphate,
Disodium EDTA, BHT
Disodium EDTA
BHT – butylated hydroxytoluene, BHA - butylate hydroxyanisole
Tocopheryl acetate does not have a stabilizing effect during storage; however, some cosmetic products state its
antioxidant activity.
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jocd_13852_f1.docx
16
0.04
14
0.03
12
0.02
0.01
m/m ‰
10
8
0.00
Rpal βcar
R
βcar
(F11) (F11) (F11) (F12)
6
Initial content
6 months, 25⁰C
6 months, 40⁰C
4
2
0
R Rpal R
R
R Rpal R Rpal HPR Rpal Rpal Rpal Rpal βcar R βcar
(F1) (F2) (F3) (F4) (F5) (F6) (F7) (F3) (F8)* (F9) (F10) (F4) (F11) (F11) (F11) (F12)
Figure 1. Comparison between the initial content of retinol (R), retinyl palmitate (Rpal), β
carotene (βcar), and hydroxypinacolone retinoate (HPR) in the tested cosmetics formulations
(F) and their remaining contents after 6 months at 25 °C and 40 °C.
*The presented content for HPR in F8 is the result after 3 months of storage at 40 °C because
of latter stratification.
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First order constant k (month -1)
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0.30
0.25
0.20
R
0.15
Rpal
0.10
HPR
0.05
β car
0.00
0
2
4
6
8
10
12
14
Initial retinoid contents (m/m ‰)
Figure 2. First-order reaction rate constants of retinoids degradation in the tested cosmetics in
association with their initial contents.
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jocd_13852_f3.docx
First order constant k (month -1)
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0.30
0.25
0.20
R
0.15
Rpal
0.10
HPR
β car
0.05
0.00
0
20
40
60
80
100
120
Price (€)
Figure 3. First-order reaction rate constants of retinoids degradation in the tested cosmetics in
association with their price.
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14
12
m/m ‰
10
8
0.03
0.02
0.01
Initial content
0.00
6
Rpal βcar
R
βcar
(F11) (F11) (F11) (F12)
1 week, 40⁰C
1week, UV
4
2
0
R Rpal R
R
R Rpal R Rpal HPR Rpal Rpal Rpal Rpal βcar R βcar
(F1) (F2) (F3) (F4) (F5) (F6) (F7) (F3) (F8) (F9) (F10) (F4) (F11) (F11) (F11) (F12)
Figure 4. Comparison between the initial content of retinol (R), retinyl palmitate (Rpal), β
carotene (βcar) and hydroxypinacolone retinoate (HPR) in the tested cosmetics formulations
(F) and their remaining contents after 1 week at 40 °C and exposure to light.
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