Influence of Emollient on The Penetration and The Stability of Sodium
Ascorbyl Phosphate Cream
Yanni Dhiani Mardhiani, Deny Puriyani Azhari, Silviana Wulansari
Research Group of Pharmaceutics, Bandung School of Pharmacy,
Bandung, West Java, 40266, Indonesia
Received : 24 Sept 2018/Revised : 6 Nov 2018/Accepted : 9 Des 2018/Published : 21 Jan 2019
ABSTRACT
Sodium ascorbyl phosphate (SAP) often used in topical formulation due to its more stable properties than
ascorbic acid. However, it is difficult to deliver SAP into the dermis in a sufficient dose. To overcome the
problem, occasionally we can add a penetration enhancer. In some literature, emollients that often added in
cosmetic preparations also have another effect as a penetration enhancer. The purpose of this research was
to observe whether emollient addition could influence the penetration of SAP in the cream formulation.
SAP was formulated into four formulations with three different emollients: dimethicone (F1), capric
triglyceride (F2), isopropyl myristate (F3) and a formulation without emollient addition (F4). The diffusion
test was performed using male wistar rat’s abdominal membrane as a standard model of the skin barrier.
The result of stability test showed that SAP cream was stable at room temperature but unstable on freeze
thaw condition described by significant different values for all formulas. Nonetheless, the diffusion test
showed that F2 had the highest ability to pass SAP through the membrane, followed by F3 and F1. We
concluded that emollient addition could influence the penetration of the SAP cream.
Keywords: vitamin c, ascorbic acid, sodium ascorbyl phospate, emollient, penetration enhancer
1. Introduction
In cream preparations, vitamin C is an active
ingredient that very unstable because it is easily
oxidized [1], in the presence of light, water, and air
that can decompose vitamin C in the form of L-
ascorbic acid into L-dehydroascorbat (DHA) and
then changed to L-gluconic acid and oxalate as non
active ingredient [1, 2]. To overcome this stability
problem, it is often used ascorbic acid derivative,
namely SAP, magnesium ascorbyl phosphate,
ascorbyl palmitate, ascorbyl glucoside, and calcium
ascorbyl as more stable form of vitamin C [3].
However it is difficult to deliver SAP into the
dermis in the optimum dosage. To overcome the
problem, occasionally we can add penetration
enhancer [4]. Emollients usually was added in
cream preparation as moisturizers when applied to
the skin [5]. It can also act as penetration enhancers
of the active substance [6]. The effect of increased
penetration of active substance by emollients can
be obtained from the modification of the type or
number of emollients used, or their combination
with emulsifiers [7]. The effect of increasing
penetration of emollients can occur due to the
hydration mechanism of the skin with occlusion
and moisturizing effects, other mechanisms that
may occur are increased solubility of active
compounds in the stratum corneum and changes in
the structure of intercellular lipids by changes in
brick and mortar conformation in the stratum
corneum [8, 9]. There is several categories of
emollients [10], In this study, it was done by
comparing the penetration ability by using three
different emollients based on its chemical class i.e.,
Tegosoft M® (Isopropil Miristate) as polar
emollient [11], Tegosoft CT® (Capric
Triglycerides) as nonpolar natural oil [12], and Abil
350® (Dimeticon) as non polar skin conditioning
agent.
*Corresponding author, https://doi.org/10.24198/idjp.v1i1.19582
e-mail : yanni.dhiani@stfb.ac.id 2019 Mardhiani et al
Vol 1, Issue 1, 2019 (33-39)
http://journal.unpad.ac.id/IdJP
Y.D. Mardhiani et al / Indo J Pharm 1 (2019) 33-39
34
2. Method
The first stage of this study was optimization of
cream base by varying the concentration of the
emulgators then evaluated including organoleptic,
pH, and viscosity. Base optimization was done by
making 5 formulas with different emulgator
concentrations, the emulgator used was Fancor uni-
embase, in which already contains a combination of
several emulgators that are formulated in such a
way as to form a stable cream base. The fancor uni
embasse concentration used was 17%, 19%, 21%,
23%, and 25% formulated with other excipients
such as preservative DMDM hydantoin, and
aquademin as solvents. The base was evaluated by
simple stability test which it was stored for 7 days
at room temperature, then compared statistically to
determine the best formula [13].
After getting the best emulgator concentration,
the next step is the cream formulation of SAP as we
presented in table 1.
After the cream preparations were made,
evaluation of the preparations included organoleptic,
viscosity measurement, pH measurement, scattering
power test and homogenity, emulsion type test,
accelerated centrifugation test was done [14].
Stability evaluation was presented for 28 days at
room temperature storage and Freeze and Thaw
method. This test was carried out for 6 cycles in
which 1 cycle consisted of storage at 40
o
C for 48
hours then transferred to storage at 4
o
C for 48
hours. Then evaluated by observing the
organoleptic and measuring the pH value and
viscosity as a parameter of stability of a preparation
[15].
Penetration rate testing of active SAP contained
in cream preparations using franz cell diffusion
method. The membrane used was the skin of male
Wistar mice. The test cream sample was weighed
1,0 g and flattened on the membrane. The media
temperature was 37 ± 1ºC with a total volume of
phosphate buffer pH 7,4 as 15 mL receptor fluid for
8 hours. Then the concentration of SAP was
determined spectrophotometrically at a wavelength
of 258 nm [16, 11].
3. Result
3.1 Cream base optimization
Based on the evaluation and statistical analysis
of the cream base during 7 days simple stability test
including organoleptic, viscosity, and pH, F1 with
a 17% emulgator concentration was chosen as the
cream base which was then used for the SAP cream
formulation.
3.2 SAP cream evaluation
3.2.1. Organoleptic and homogeneity evaluation
Organoleptic and homogeneity evaluation of
SAP cream was presented good appearance and
homogeneity during 28 days storage at room
temperature
3.2.2. Centrifugation Test
The observations of centrifuged tests showed
that the cream of SAP from F1 to F4 is physically
stable where phase separation does not occur.
3.2.3. Emulsion Type Test
Observations on all formulas with methylene
blue method showed that the type of SAP cream in
this study is oil in water.
3.2.4. Room temperature stability test
Organoleptically, based on pH, viscosity and
dispersion test observation, there was no significant
differences among all formula during 28 days.
The measurement pH results of all formulas can
be seen in figure 1. The results of data analysis with
the one way anova method showed that there were
significant differences between viscosity to storage
time in all formulas from day 1 to day 28. The
measurement results of F1, F2, F3, and F4 viscosity
can be seen in figure 2. The value of SAP cream
spreadability can be seen in Figure 3.
3.2.5. Freeze and thaw stability test
Organoleptic examination performed every 1
cycle for 6 cycles of accelerated stability testing,
including examination of color, odor, and cream
dosage form. It showed discoloration in the 2nd
cycle to the 6th cycle. pH evaluation of SAP cream
at freeze thaw stability test can be seen in Figure 4.
Viscosity evaluation of SAP cream at freeze thaw
Y.D. Mardhiani et al / Indo J Pharm 1 (2019) 33-39
35
stability test can be seen in Figure 5. Diffusion test
of SAP cream can be seen in Figure 6.
Table 1. Formulation of SAP cream
Concentration (%)
Materials
F1
F2
F3
SAP
1.5
1.5
1.5
DMDM Hydantoin
0.6
0.6
0.6
Na-Metabisulfite
0.1
0.1
0.1
Fancor uni embasse
17
17
17
Abil 350
®
1.0
-
-
Tegosoft CT
®
-
1.0
-
Tegosoft M
®
-
-
1.0
Citric acid
0.5
0.5
0.5
Aquademineral
up to
up to
up to
100
100
100
Note : Fancor uni embase: Cream base; Tegosoft M®: Isopropil Miristat; Tegosoft CT®:
Capric Triglycerides; Abil 350®: Dimetikon
8.00
7.00
6.00
5.00
4.00
3.00
2.00
1.00
0.00
F1 F2 F3 F4
Formula
Figure 1. Graph of SAP cream pH in the room temperature stability test
day 1
day 3
day 5
day 7
day 14
day 21
day 28
Note: [F1: Abil 350
®
; F2: Tegosoft CT
®
; F3: Tegosoft M
®
; F4: no emollient]
50000
40000
30000
20000
10000
0
F1 F2 F3 F4
Formula
day 1
day 3
day 5
day 7
day 14
day 21
day 28
Figure 2. Graph of SAP cream viscosity at room temperature storage
Note: [F1: Abil 350
®
; F2: Tegosoft CT
®
; F3: Tegosoft M
®
; F4: no emollient]
pH
Viscosity (cPs)
Y.D. Mardhiani et al / Indo J Pharm 1 (2019) 33-39
36
10.00
8.00
6.00
4.00
2.00
0.00
F1 F2 F3 F4
Formula
day 1
day 3
day 5
day 7
day 14
day 21
day 28
Figure 3. Graph of spreadability value at room temperature storage
Note: [F1: Abil 350
®
; F2: Tegosoft CT
®
; F3: Tegosoft M
®
; F4: no emollient]
10.00
8.00
6.00
4.00
2.00
0.00
F1 F2 F3 F4
Formula
cycle 1
cycle 2
cycle 3
cycle 4
cycle 5
cycle 6
Figure 4. Graph of pH value at freeze thaw stability test
Note: [F1: Abil 350
®
; F2: Tegosoft CT
®
; F3: Tegosoft M
®
; F4: no emollient]
50000
40000
30000
20000
10000
0
F1 F2 F3 F4
Formula
cycle 1
cycle 2
cycle 3
cycle 4
cycle 5
cycle 6
Figure 5. Graph of viscosity value at freeze thaw stability test
Note: [F1: Abil 350
®
; F2: Tegosoft CT
®
; F3: Tegosoft M
®
; F4: no emollient]
Diameter (cm)
Viscosity (cPs)
pH
Y.D. Mardhiani et al / Indo J Pharm 1 (2019) 33-39
37
1000
900
800
700
600
500
400
300
200
100
0
F1
F2
F3
F4
1 2 3 4 5 6 7 8
Time (hour)
Figure 6. Graph of diffusion test of SAP cream
Note: [F1: Abil 350
®
; F2: Tegosoft CT
®
; F3: Tegosoft M
®
; F4: no emollient]
4. Discussion
From the result of organoleptic and
homogeneity evaluation, SAP cream was presented
good appearance and homogeneity during 28 days
storage at room temperature, thus physically
stable.
Based on the results of the data analysis of figure
1, the pH value of each formula on storage time
during 28 days at room temperature using the one
way Anova method, it was found that F1 and F3
had a significance value> 0.05, so there was no
significant difference from pH values F1 and F3
during the day 1 to 28 days, while F2 and F4 there
are significant differences (sig <0.05), so it can be
concluded that F1 and F3 are stable in the storage
period while F2 and F4 are unstable during the
storage period. Meanwhile, there were significant
differences between viscosity at the same condition
in all formulas from day 1 to day 28. The
measurement results can be seen in figure 2.
At figure 3, the value of the dispersibillity at
room temperature is in the range of 4.7 - 5.7 cm. It
was related to the influence of the viscosity value
which it was inversely proportional to the viscosity.
If there is an increasing in viscosity value, the
dispersibillity value will be decreased from day 1 to
28. Spreadability values of all formulas have
qualify the spreadability standard (in the range of
5-7 cm). One way anova analysis showed a
significant difference in all formulas.
In the freeze thaw stability test, it showed
discoloration in the 2nd cycle to the 6th cycle, this
color change presennted oxidation of the active
substance due to heating when the preparation was
stored at 40
o
C. Then in the 4th cycle the preparation
becomes a scorched or rancid odor, this can happen
because in the cream preparations contained
ingredients such as emulsifiers and emollients
which are oil or fat ingredients so that when stored
at high temperatures will result in oxidation of the
oil content which can cause rancidity.
At figure 4, the results of pH evaluation at freeze
thaw test data analysis using One Way Anova
showed a significant difference in all formulas (sig
<0.05). It showed that all formulas are not stable in
periods of storage with extreme temperatures based
on pH values, this can be caused by the influence
of media which are decomposed by high
temperatures during the manufacturing or storage
process that produces acidic or basic substances, so
this can affect the pH value.
At figure 5, the graph showed that F1 had the
most stable viscosity value. Based on one way
anova analysis, presented that F1 has a significance
value ( sig > 0.05). The emulsion viscosity will
decrease if the temperature is high, and will
increase when the temperature is low. This is
because the heat obtained will increase the distance
between atoms so that the force between atoms will
decrease, the distance becomes tenuous resulting in
the viscosity of the cream decreasing. After the
cream has cooled there will be a release of water to
the cream, but if the emulsifying film can work
again under ice-induced pressure before
coalescence occurs then the emulsion system will
Q (µg/cm2)
Y.D. Mardhiani et al / Indo J Pharm 1 (2019) 33-39
38
stabilize. Temperature can affect the viscosity
where high temperatures can reduce viscosity,
conversely low temperatures can increase viscosity
[17].
The results of diffusion of sodium ascorbyl
phosphate cream at figure 6 showed differences in
the percentage of active substances that diffuse
between F1, F2, F3, and F4. F1 and F4 tend to have
a cumulative number of penetrated (Q) active
substances that are almost the same, F3 has a high
Q value and F2 reaches the highest Q value. This is
related to the different types of emollients used in
cream formulations, where F1 using dimethicon
1% produces the same Q value as F4 as a negative
control that does not use emollients, indicating that
in this study dimethicone has no potential to
increase the penetration of active substances,
whereas F3 using isopropyl myristate as emollient
has a sufficiently high diffused cumulative value,
indicating that in this study isopropyl myristate can
increase the penetration of active substances, and
F2 using capric triglycerides has the potential to
increase the penetration of the active substance
most compared to isopropyl myristate and
dimethicone. This is related to the different polarity
of the three types of emollients [8].
5. Conclusion
It could be concluded that cream formula which
employ capric triglyceride as emollient had the
highest ability to pass SAP through the membrane,
followed by isopropyl miristate, and dimethicone.
Therefore the addition of emollient could influence
the penetration of the active substance in
formulation.
Acknowledgement
This research was supported and in part by the
Internal Research Program of Bandung School of
Pharmacy, Indonesia.
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