J Therm Anal Calorim
DOI 10.1007/s10973-016-5654-9
Compatibility study between ferulic acid and excipients used
in cosmetic formulations by TG/DTG, DSC and FTIR
Gilberto Silva Nunes Bezerra1 • Maxciara Agda Vicente Pereira1 • Elissa Arantes Ostrosky1
Euzébio Guimarães Barbosa1 • Maria de Fátima Vitória de Moura2 • Marcio Ferrari1 •
Cı́cero Flávio Soares Aragão1 • Ana Paula Barreto Gomes1
Received: 5 February 2016 / Accepted: 16 June 2016
 Akadémiai Kiadó, Budapest, Hungary 2016
Abstract Ferulic acid (4-hydroxy-3-methoxycinnamic
acid) is a phytochemical constituent from the polyphenols
group commonly found in whole grains, spinach, parsley,
grapes and rhubarb. It has been widely applied in skin care
formulations as photoprotective agent and delayer of
cutaneous photoaging processes. This work aims to estab-
lish a protocol to the development of cosmetic formulations
using thermoanalytical techniques (TG/DTG and DSC) and
Pearson’s correlation by FTIR data, in order to evaluate the
compatibility between ferulic acid and excipients used in
skin care formulations. The results obtained from the
thermoanalytical techniques indicated compatibility
between ferulic acid and the following excipients: passion
fruit seed oil, Carbopol Ultrez 30, EDTA, Crodabase
CR2, CrodamolTM GTCC and Dow Corning RM 2051.
Nevertheless, the analysis also demonstrated the possibility
of some interaction between ferulic acid and the following
excipients: glyceryl stearate, Rapithix A-60 and
Optiphen. To validate these results, it was demonstrated
by Pearson’s correlation that passion fruit seed oil, Car-
bopol Ultrez 30, EDTA, Crodabase CR2, CrodamolTM
GTCC, Dow Corning RM 2051, glyceryl stearate and
Rapithix A-60 do not have any incompatibility that may
compromise ferulic acid properties. Finally, it was also
proved a meaningful incompatibility between ferulic acid
& Ana Paula Barreto Gomes
ana.pbgomes@gmail.com
1
Pharmaceutical Sciences Department, Federal University of
Rio Grande do Norte – UFRN, Av. Gal. Gustavo de Farias
s/n, Petrópolis, Natal, RN 59078-970, Brazil
2 antioxidant potential is directly related to its chemical
Institute of Chemistry, Federal University of Rio Grande do
Norte – UFRN, University Campus, Natal, RN 59072-970,
Brazil
•
and Optiphen using Pearson’s correlation. Thus, it is not
recommended to use Optiphen in the development of
cosmetic formulations to carry ferulic acid.
Keywords Compatibility study
Cosmetic formulation

Ferulic acid
FTIR
Thermoanalytical techniques
Introduction
Ferulic acid (4-hydroxy-3-methoxycinnamic acid) (Fig. 1)
is a ubiquitous plant constituent derivative from cinnamic
acid [1], which is the most abundant phenolic acid present
in whole grains, spinach, parsley, grapes and rhubarb [2].
Plant polyphenols are secondary metabolites synthesized
mainly to fight against biotic and abiotic stresses, such as
pathogens and ultraviolet (UV) radiation. These molecules
are characterized by having several hydroxyl groups
attached to aromatic rings, and they are structurally divided
into different chemical groups. The most promising ones
for human health include phenolic acids, flavonoids, stil-
benes and lignans [1].
Many studies have demonstrated the beneficial proper-
ties of ferulic acid (FA), including therapeutic properties
against several kinds of cancer, for instance breast [3, 4],
lung [5], colon [6] and skin cancer [7]. Moreover, it also
demonstrated anti-diabetic effect [8], protection against
Alzheimer’s disease [9] and therapeutic potential for the
treatment of mood disorders as depression [10].
FA is not only a free radical scavenger, but also an
enhancer of scavenger enzymes activity and an inhibitor of
enzymes that catalyze free radical generation [11]. This FA
structure; in other words, any reactive species is able to
abstract the hydrogen atom creating the phenoxyl radical;
123

H3CO COOH
HO
Fig. 1 Representation of the chemical structure of ferulic acid
however, the benzene ring and the double bond conjugated
with the carboxylic group are able to promptly stabilize this
radical through resonance mechanism [12].
Particularly, acute or chronic UV radiation may induce
the production of reactive oxygen species (ROS) and
reactive nitrogen species (RNS), which are able to cause
premature skin aging, erythema, inflammation and photo-
carcinogenesis [12]. Hence, FA has been widely applied in
skin care formulations as a photoprotective agent and
delayer of skin photoaging processes [13]. In addition, its
application as a topical antioxidant became an important
administration route due to the low cutaneous metabolism,
maintaining a high local concentration [14].
Preformulation studies are extremely important to pre-
dict physical (solid-state interaction) and/or chemical
interactions between the active pharmaceutical ingredient
(API) and excipients. A solid-state interaction can not only
result in polymorphism formation or changing of poly-
morphic form, but also cause the API’s solubilization with
the excipient creating intermolecular interactions among
their functional groups. At the same time, a solid-state
interaction cannot be considered an incompatibility if the
excipients do not alter the results from the API’s assay.
According to many authors, an incompatibility phe-
nomenon comes from chemical reactions between the API
and excipient that can lead to the active ingredient’s
degradation resulting in new degradation products or
impurities that can change quality, safety and efficiency of
medicinal or cosmetic formulations [15–18].
We can say that the first method chosen to evaluate the
compatibility between the API and excipients is the ther-
mal analysis. Among the thermal techniques, the DSC and
TG are the most used with this purpose. Sohn and Oh [19]
conducted a compatibility study between FA and excipi-
ents commonly used in solid dosage forms using thermal
technique. Consequently, they identified important incom-
patibilities to many of the excipients analyzed. In the lit-
erature, there are many other examples of preformulation
studies applying thermoanalytical techniques with strong
evidences of interactions and incompatibilities [20–23].
Although the events related to the sample can be better
characterized through association of data obtained from
two different thermal techniques, their subsequent associ-
ation with results obtained from another analytical tech-
nique is essential to interpret and confirm these events [15].
123
G. S. N. Bezerra et al.
Moyano et al. [21] evaluated the thermal compatibility
between lipoic acid and some cosmetic excipients obtain-
ing suggestive results of interactions. Consequently to
confirm these results, avoid misinterpretation and unreli-
able conclusions through the evaluation, binary mixtures
were analyzed by other analytical techniques, such as IR
spectroscopy and isothermal stress testing (IST) with the
HPLC support. Thus, lipoic acid was found to be incom-
patible with many of the excipients under study.
Several reports are described in the literature to evaluate
the interactions between API and excipients using thermal
and non-thermal techniques, for example Fourier trans-
formed infrared spectroscopy (FTIR), HPLC, LC–MS/TOF
and LC/UV applying mathematical and statistical models
to correlate and analyze the results obtained [21–30].
Since there are not any previous data concerning the FA
thermal behavior with excipients used to the development
of cosmetic formulations, this work evaluated the physical
and chemical properties between FA and excipients used in
skin care formulations applying thermoanalytical tech-
niques (TG/DTG and DSC) and Pearson’s correlation by
FTIR data.
Materials and methods
The present study was conducted at the Laboratory of
Research and Development of Cosmetic Products, the
Laboratory of Quality Control (LCQmed) and the Institute
of Chemistry (IQ) from the Federal University of Rio
Grande do Norte (UFRN).
Materials
Ferulic acid was purchased from Henrifarma Produtos
Quı́micos e Farmacêuticos Ltda. (São Paulo, Brazil). The
excipients are described by the INCI name: carbomer
(Carbopol Ultrez 30 Polymer) from Lubrizol Advanced
Materials, Inc. (Ohio, USA); sodium polyacrylate (and)
hydrogenated polydecene (and) trideceth-6 (Rapithix
A-60) from Ashland, Inc. (São Paulo, Brazil); sodium
polyacrylate (and) dimethicone (and) cyclopentasiloxane
(and) trideceth-6 (and) PEG/PPG 18/18 dimethicone (Dow
Corning RM 2051) from D’Altomare Quimica (São Paulo,
Brazil); cetearyl alcohol (and) steareth-20 (and) steareth-10
(and) paraffinum liquidum (and) lanolin alcohol (and)
petrolatum (and) lanolin (and) oleyl alcohol (Crodabase
CR2) from Croda do Brasil Ltda. (São Paulo, Brazil);
glyceryl stearate (MEG) from Gramalux (São Paulo, Bra-
zil); caprylic/capric triglyceride (CrodamolTM GTCC) from
Croda do Brasil Ltda. (São Paulo, Brazil); phenoxyethanol
and caprylyl glycol (Optiphen) from Ashland, Inc. (São
Paulo, Brazil); ethylenediaminetetraacetic acid, disodium
Compatibility study between ferulic acid and excipients used in cosmetic formulations by…
salt (EDTANa2) from Fagron do Brasil Farmacêutica Ltda.
(São Paulo, Brazil); passion fruit seed oil from Plantus (Rio
Grande do Norte, Brazil); and distilled water. The excipients
and their respective properties are shown in Table 1.
Binary mixtures
The physical mixtures between FA and the excipients were
prepared in a ratio of 1:1 (W/W), 100 mg solid excipients
and 200 mg liquids excipients, by simply mixing with a
spatula.
Thermal analysis (TG/DTG–DSC)
TG and DSC curves of the samples were obtained using
simultaneous thermogravimetric analysis (TG) and differ-
ential scanning calorimetry (DSC), model SDTQ600,
manufactured by TA Instruments.
Ferulic acid curves were performed in triplicate using
approximately 4 mg of the sample, alumina sample con-
tainer, under nitrogen atmosphere with flow of
50 mL min-1, heating rates of 5, 10 and 20 C min-1 up to
900 C.
The excipients and binary mixtures were analyzed using
approximately 4 mg of the sample, alumina sample con-
tainer, under nitrogen atmosphere with flow of
50 mL min-1, heating rate of 10 C min-1 up to 900 C.
The software TA Instruments Universal Analysis 2000
was applied to analyze all curves and to calculate the DTG.
Also, the tangent tool was applied to analyze the TG
curves.
Fourier transformed infrared spectroscopy (FTIR)
The spectra of the samples were performed on a spec-
trophotometer ATR-FTIR (IRPrestige-21 Shimadzu),
between 700 and 4000 cm-1, on average of 20 scans per
Table 1 Raw materials used in the compatibility study
Sample
Active ingredient Ferulic acid
Excipients Carbopol Ultrez 30
Rapithix A-60

Dow Corning RM 2051
Crodabase CR2
Glyceryl stearate
CrodamolTM GTCC
Passion fruit seed oil
Optiphen
EDTA
sample, and subsequently analyzed the fingerprint region,
at a wavelength of 700–1800 cm-1.
The spectra were normalized and analyzed by an algo-
rithm of spectra comparison, based on Pearson’s correla-
tion in spectral regions of variable size. In other words, the
algorithm ad hoc creates a theoretical spectrum for the
binary mixture using a linear combination of the pure
compounds spectra. This combination is created through
normalization and arrangement of both spectra based on
the molar composition of the physical mixture. Then, the
experimental spectrum from the binary mixture was com-
pared with the theoretical spectrum, and subsequently the
appearing or fading peaks were identified. Thus, high
correlations are between 0.80 and 1.00, indicating simple
mixture of solids. Moderate correlations are between 0.5
and 0.80, indicating possible interactions. Values below
0.50 indicate low similarity between spectra, demonstrat-
ing chemical degradation [15, 22, 23].
Results and discussion
Thermal analysis of ferulic acid (FA)
Figure 2 shows the FA curves of TG/DTG and DSC in the
heating rate of 10 C min-1. In the DSC curve are seen
two endothermic peaks. The first one is attributed to the
fusion of the FA which is expected between 173 and
176 C, according to the Japanese Pharmacopeia (JP XVI)/
National Formulary (2012) [31]. The heat associated with
this first step, calculated according to Fig. 2, was
183 J g-1, and the peak temperature was 173 C. The
second event was associated with FA decomposition fol-
lowed by the oxidation of carbonaceous matter. For the
second event, endothermic enthalpy was 256 J g-1 and the
peak temperature 247 C. The mass lost related to the
endothermic events that occurred between 200 and 250 C
Classification
Antioxidant
Gelling agent, viscosity increasing agent
Thickening agent, emulsifying agent
Thickening agent, emulsifying agent
Thickening agent, emulsifying agent
Thickening agent, auxiliary emulsifying agent
Emollient
Emollient
Antimicrobial preservative
Chelating agent
123

Fig. 2 Ferulic acid thermal 110
behavior by TG (black), DTG
(red) and DSC (blue) curves, in
90
the heating rate of 10 C min-1.
(Color figure online)
70
Mass/%
50
30
10
–10
Exo Up 0 200
was 94 %, with a single peak in DTG at 240 C. The
difference corresponds to the carbonaceous residue
obtained in this step. Similar result is described in the lit-
erature, and it was demonstrated by a calorimetric study
that FA has melting peak of approximately 175 C, without
any other marked endothermic peaks, so it can be pre-
sumed that FA has a well-defined crystalline phase [19].
A third endothermic event is observed at temperature
above 600 C that can be attributed to the decomposition of
degradation products (carbonaceous matter) and their
subsequent volatilization. According to the thermogravi-
metric studies performed by Fiddler et al. [32],two transi-
tion phases attributed to FA decomposition were evidenced
under their study conditions, with the first one at 200 C
and the second one at 340 C. Subsequently using gas–
liquid chromatography (GLC), infrared (IR) spectroscopy)
and gas–liquid chromatography–mass spectrometry (GLC-
MS) techniques, FA degradation products were identified
under nitrogen atmosphere, such as guaiacol, 4-methyl-
guaiacol and 4-ethylguaiacol, and the majority in the first
decomposition transition was 4-vinylguaiacol.
Furthermore, it is extremely relevant to consider the
thermoanalytical techniques to characterize different FA
polymorphs using their specific melting points. Calorimetric
studies performed by Sohn and Oh [19] characterized and
identified two different AF polymorphic forms. The first one
shows an endothermic peak at 175 C (40.2 cal g-1 =
168.3 J g-1), while the second one shows three different
endothermic peaks at 105 (9.3 cal g-1 = 38.93 J g-1), 148
(12.8 cal g-1 = 53.59 J g-1) and 182 C (4.9 cal g-1 =
20.51 J g-1). They also concluded that the solvent used to
the recrystallization phase is crucial to the crystalline
arrangement of both polymorphic forms. Moreover,
according to the same authors, the polymorphic form I has
higher solubility in aqueous solution than the polymorphic
form II, which must be considered to the development of a
123
G. S. N. Bezerra et al.
0
2.0
Deriv. mass/mg min–1
Heat flow/mW mg–1
1.5 –2
1.0
0.5 –4
0.0
–6
400 600 800 1000
Temperature/°C
cosmetic formulation to carry FA. Thus, when our data are
compared with this previous one, we can assume that our
active ingredient is the polymorphic form I.
With regard to evaluating possible physical–chemical
interactions and incompatibilities between FA and excipi-
ents, a previous analysis of TG/DTG and DSC curves of each
pure constituent is necessary, then making their association
with the binary mixtures curves looking for some possible
alterations in the active ingredient melting peak.
Thermal study of binary mixtures
Figure 3 shows the thermal profile (TG/DTG and DSC) of
each excipient under study in the heating rate of
10 C min-1. The results obtained from the thermal com-
patibility study between FA and excipients (TG and DSC)
are shown in Fig. 4, where TG and DSC curves are over-
laid and it is possible to measure all the events related to
the binary mixtures, as well as some possible interactions
between the components. Furthermore, Table 2 shows
numerically all these thermal events.
Initially, the FA thermal behavior in the calorimetric
curve demonstrated a well-defined endothermic peak in
173 C. Thus, displacements in the onset temperatures of
the melting peak or its disappearance may indicate physical
or chemical interactions.
After analyzing the DSC curves from binary mixtures, it
can be assumed that some excipients did not affect the FA
thermal behavior without any apparent physical–chemical
change or incompatibility. Among these excipients are
included: passion fruit seed oil (Fig. 4d), Carbopol Ultrez
30 (Fig. 4g) and EDTA (Fig. 4h), which showed Tpeak 172,
171 and 170 C, respectively. Thus, these excipients did
not cause any change in FA thermal behavior; more
specifically, they did not shifted the FA Tpeak. It means that
FA and these excipients are compatible.
Compatibility study between ferulic acid and excipients used in cosmetic formulations by…

(a) 110 5 (b) 110 2 (c) 110 4

Deriv. mass/mg min–1

90 90 0 90 2

Deriv. mass/mg min–1

Deriv. mass/mg min–1

Heat flow/mW mg–1

Heat flow/mW mg–1
1.5

Heat flow/mW mg–1

0 1.0
–2 0
70 0.4 70 70

Mass/%

Mass/%
1.0
Mass/%

–4 –2
50 –5 50 0.5 50
–6 0.5 –4
30 0.2 30 30
–8 –6
–10 0.0
0.0
10 10 –10 10 –8

–10 –15 –10 –12 –10 –10

0 200 400 600 800 1000 0 200 400 600 800 1000 0 200 400 600 800 1000
Exo up Temperature/°C Exo up Temperature/°C Exo up Temperature/°C

(d) 110 5 (e) 110 5 (f) 110 5

90

Heat flow/mW mg–1

Heat flow/mW mg–1
0.6 0 90 0 90 2.0

Deriv. mass/mg min–1

Deriv. mass/mg min–1

Deriv. mass/mg min–1

Heat flow/mW mg–1

0
70 70 0 . 4 –5 70 1.5

Mass/%

Mass/%
0 . 4 –5
Mass/%

50 50 –10 50 1.0 –5
0 . 2 –10
30 30 0 . 2 –10 30 0.5
–10
0 . 0 –15 –15
10 10 10 0.0

–10 –20 –10 –20 –10 –15

0 200 400 600 800 1000 0 200 400 600 800 1000 0 200 400 600 800 1000
Exo up Temperature/°C Exo up Temperature/°C Exo up Temperature/°C

(g) 110 2 (h) 110 5 (i) 110 2

90 0 90 90 0
Deriv. mass/mg min–1

Deriv. mass/mg min–1

Heat flow/mW mg–1

Heat flow/mW mg–1

Heat flow/mW mg–1

Deriv. mass/mg min–1
1.0 2
–2
70 –2 70 0.4 70
Mass/%

Mass/%
Mass/%

–5 –4
50 0.5 –4 50 50 1
–6
–10
30 –6 30 0.2 30
–8
0.0 0
–15
10 –8 10 10 –10

–10 –10 –10 –20 –10 –12

0 200 400 600 800 1000 0 200 400 600 800 1000 0 200 400 600 800 1000
Exo up Temperature/°C Exo up Temperature/°C Exo up Temperature/°C

Fig. 3 TG/DTG and DSC curves of the excipients in the heating rate of 10 C min-1. a Carbopol Ultrez 30, b Crodabase CR2, c Glyceryl
Stearate, d EDTA, e Rapithix A-60, f CrodamolTM GTCC, g passion fruit seed oil, h Dow Corning RM 2051 and i Optiphen

(a) a (b)
b a
c
b
c
Heat flow/mW mg–1

d d
e e
f
Mass/%

f
g
h g
i
h
j i

0 200 400 600 800 1000 Exo up 0 200 400 600 800 1000
Temperature/°C Temperature/°C

Fig. 4 Overlay TG (a) and DSC (b) curves of ferulic acid and binary e Glyceryl Stearate, f Rapithix A-60, g Carbopol Ultrez 30, h EDTA,
mixtures 1:1 (w/w) in heating rate of 10 C min-1. a ferulic acid, i Optiphen and j Dow Corning RM 2051
b CrodamolTM GTCC, c Crodabase CR2, d passion fruit seed oil,

With regard to Crodabase CR2 (Fig. 4c), CrodamolTM endothermic peak in the calorimetric curve, which is
GTCC (Fig. 4b) and Dow Corning RM 2051 (Fig. 4j), characteristic of the base melting point in Tonset 34 C
these excipients had small displacements in Tpeak 169, 168 (DH = 81 J g-1, Tpeak = 43 C) followed by a mass loss
and 167 C, respectively, which can be an indicative of in the TG curve (Dm = 1 %) between 23 and 62 C, with a
physical interaction. peak in DTG (Tpeak/DTG = 50 C). It can be inferred that
Crodabase CR2 is a creamy solid base with melting this excipient melts earlier than FA. CrodamolTM GTCC
point between 36 and 45 C [33]. Figure 3b shows a single (Fig. 3f) and Dow Corning RM 2051 (Fig. 3h) both are

123
 G. S. N. Bezerra et al.

Table 2 Thermoanalytical data of binary mixtures 1:1 (w/w) between FA ? excipients in the heating rate of 10 C min-1
Binary mixtures 1:1 (W/W) DSC TG DTG
-1 a
Transition Event Tonset/C Tpeak/C DH J g DT/C Dm/% Tonset/C Tpeak/C Dm/%

Carbopol Ultrez 30 1 Endo 22 48 151 22–61 4 30 49 0.2

2 Endo 167 171 66 61–215 34 165 198 2.8
3 Endo 191 228 96 215–256 12 232 246 0.1
4 Exo 353 381 239 256–416 23 341 361 1.2
5 Exo 423 455 203
Rapithix A-60 1 Endo 124 147 52 107–177 38 140 164 3.7
2 Endo 159 171 19 177–321 29 232 300 0.8
321–393 9 357 381 0.2
393–509 7 412 430 0.4
3 Endo 855 864 230 822–900 7 844 861 0.6
Dow Corning RM 2051 1 Endo 24 66 112 24–90 7 37 75 0.3
2 Endo 163 167 40 90–191 57 163 182 4.7
3 Endo 177 189 47 191–256 10 234 250 0.03
256–384 9 365 378 0.1
384–496 4 411 453 0.1
4 Exo 761 815 252 767–872 4 814 839 0.3

Crodabase 1 Endo 35 47 34
2 Endo 165 169 68 126–212 64 190 207 5.2
3 Endo 200 210 115 212–271 27 245 262 0.2
271–400 6 328 353 0.1
Glyceryl Stearate 1 Endo 56 63 95
2 Endo 148 163 31 112–214 38 191 208 3.7
3 Endo 198 210 93 214–409 55 320 380 3.6
4 Endo 342 383 80
TM
Crodamol GTCC 1 Endo 160 168 63 150–217 42 201 213 4
2 Endo 206 215 97 217–303 49 262 296 3
3 Endo 278 300 58
Passion fruit seed oil 1 Endo 169 172 46 141–208 38 174 193 3.9
2 Endo 187 203 44 208–391 43 336 375 2.9
391–478 9 422 444 0.06
Optiphen 1 Endo 163 168 10 64–160 47 104 142 2.4
2 Endo 178 192 46 160–196 41 170 188 2.3
249–387 4 272 316 0.2
EDTA 1 Endo 166 170 392 105–192 42 167 184 4
2 Endo 240 248 177 192–274 16 240 256 0.9
3 Exo 356 376 664 274–413 16 327 368 0.7
4 Exo 533 551 208 534–595 3 537 552 0.1
5 Exo 770 794 220
6 Exo 833 841 39
a
DT ranges between Tonset and Tendset

viscous liquid. Thus, it can be assumed that these excipi-
ents likely solubilized part of FA crystalline form causing a
small shift in its melting point.
For the following excipients glyceryl stearate (Fig. 4e),
Rapithix A-60 (Fig. 4f) and Optiphen (Fig. 4i), we
assume that there are strong interactions between FA and
these excipients because the active ingredient melting peak
almost disappeared and/or Tpeak is not possible to be pre-
cisely determined.
Glyceryl stearate has melting point between 54 and 64 C
[34]. Figure 3c shows an endothermic peak characteristic of
the excipient melting point in Tonset 57 C (DH = 208 J g-1,

123
Compatibility study between ferulic acid and excipients used in cosmetic formulations by…

(a) (b)
1.0 1.0

Relative intensities
Relative intensities

0.8 0.8

correlation
correlation

0.6 0.6
0.4 0.4
0.2 0.2
0.0 0.0

4000 3500 3000 2500 2000 1500 1000 500 4000 3500 3000 2500 2000 1500 1000 500
Wavenumber/cm–1 Wavenumber/cm–1
(c) (d)
1.0 1.0

Relative intensities
Relative intensities

0.8 0.8

correlation
correlation

0.6 0.6
0.4 0.4
0.2 0.2
0.0 0.0

4000 3500 3000 2500 2000 1500 1000 500 4000 3500 3000 2500 2000 1500 1000 500
Wavenumber/cm–1 Wavenumber/cm–1
(e) (f)
1.0 1.0

Relative intensities
Relative intensities

0.8 0.8

correlation
correlation

0.6 0.6
0.4 0.4
0.2 0.2
0.0 0.0

4000 3500 3000 2500 2000 1500 1000 500 4000 3500 3000 2500 2000 1500 1000 500
Wavenumber/cm–1 Wavenumber/cm–1
(g) (h)
1.0 1.0
Relative intensities
Relative intensities

0.8 0.8
correlation
correlation

0.6 0.6
0.4 0.4
0.2 0.2
0.0 0.0

4000 3500 3000 2500 2000 1500 1000 500 4000 3500 3000 2500 2000 1500 1000 500
Wavenumber/cm–1 Wavenumber/cm–1

Fig. 5 Comparison analysis with the expected (theoretical) spectrum a Carbopol Ultrez 30, b Crodabase CR2, c CrodamolTM GTCC ,
(black) and the experimental one (blue). Red line is the results for the d Dow Corning RM 2051, e EDTA, f Glyceryl Stearate, g passion
Pearson’s correlation implemented in an ad hoc algorithm. fruit seed oil, and h Rapithix A-60. (Color figure online)

1.0 Tpeak = 62 C) as a subtle mass loss that is unfeasible to

calculate individually, with a peak in DTG (Tpeak/DTG
Relative intensities

0.8
= 62 C). It can be assumed that glyceryl stearate melts
correlation

0.6
earlier than FA crystalline form, so it is needed to consider
0.4 the possibility of this excipient has almost disappeared with
0.2 1082 FA melting peak as a physical interaction as well.
1496
0.0 1242 Rapithix A-60 (Fig. 3e) is a viscous liquid that begins
to release gases and vapors from 100 C [35] with a mass
1550 1500 1450 1400 13501300 1250 1200 1150 1100 1050
loss in the TG curve (Dm = 6 %) in the range of
Wavenumber/cm–1
22–136 C, with a peak in DTG (Tpeak/DTG = 90 C). This
Fig. 6 Spectral comparison helped to pinpoint three peaks that mass loss transition in the TG curve is possibly attributed
appeared in the experimental spectrum (blue) for FA ? Optiphen. to loss of water molecules and releases of vapors.
(Color figure online) Optiphen (Fig. 3i) shows a single endothermic event in

123
 G. S. N. Bezerra et al.

the DSC curve that can be attributed to the sample degra- Optiphen by receiving and donating hydrogen bonds,
dation in Tonset 132 C (DH = 339 J g-1, Tpeak = 171 C) destabilizing the structural profile of the active ingredient.
as a mass loss in the TG curve (Dm = 89 %) between 77
and 174 C, with a peak in DTG (Tpeak/DTG = 167 C).
Conclusions
Thus, it can be assumed that Rapithix A-60 and
Optiphen likely solubilized FA crystalline form before
The rational development of a cosmetic formulation must
losing water molecules, although it seems that both are not
be supported by a previous study to determine possible
causing just a physical but a chemical interaction.
incompatibilities that can happen between the active
Thus, we have strong evidences of some incompatibility
ingredient and excipients, which through physical and
phenomena based on the FA melting peak alterations;
chemical interactions can compromise the stability, safety
however, these incompatibilities need to be investigated by
and efficacy of the final product. Therefore, the thermal
another analytical technique as the Fourier transformed
studies can be considered essential before the development
infrared spectroscopy (FTIR) to confirm or exclude these
of a cosmetic formulation, since it can be applied as a quick
phenomena.
tool for selecting and optimizing the components choice.
In our study, the thermoanalytical techniques were
Compatibility study of the binary mixture by FTIR
extremely valuable to identify the excipients that possibly
would not have any incompatibility with FA, as follows:
The Fourier transformed infrared spectroscopy (FTIR) is a
passion fruit seed oil, Carbopol Ultrez 30, EDTA, Crod-
technique that has demonstrated to be extremely efficient to
abase CR2, CrodamolTM GTCC and Dow Corning RM
investigate possible chemical interactions as a result of the
2051. However, the excipients glyceryl stearate, Rapithix
physical mixture, FA ? excipients. Therefore, it has been
A-60 and Optiphen would be possibly altering the phys-
used as a supplementary technique to confirm the results
ical and chemical properties of the active ingredient due to
obtained from the thermal analysis [15, 22, 23]. Figure 5
some incompatibility phenomena.
shows Pearson’s correlation comparison analysis for every
To validate these data, it was confirmed by Pearson’s
binary mixture that does not have reasonable deviations
correlation that passion fruit seed oil, Carbopol Ultrez 30,
from the theoretical and experimental spectra. Some
EDTA, Crodabase CR2, CrodamolTM GTCC, Dow
deviations presented as peaks in correlation analysis were
Corning RM 2051, glyceryl stearate and Rapithix A-60
discarded when indication differences in intensity or at
do not have any incompatibility that can compromise FA
baselines’ noise.
properties, which ensured their utilization to the develop-
Binary mixtures between AF ? passion fruit seed oil,
ment of new skin care formulations.
Carbopol Ultrez 30 and EDTA showed correlation value
Finally, a significant incompatibility between FA and
very close to one (r = 1), which ensure the compatibility
Optiphen using Pearson’s correlation was also confirmed.
between FA and these excipients. Binary mixtures between
Thus, it is not recommended to use Optiphen in the
FA ? Rapithix A-60, Dow Corning RM 2051, glyceryl
development of cosmetic formulations to carry FA under
stearate, CrodamolTM GTCC and Crodabase CR2 showed
the same conditions studied by this research.
correlation around 0.9 (r = 0.9); in other words, it demon-
strated to have a very good correlation without any interaction. Acknowledgements The authors acknowledge financial support
Furthermore, the analysis of the binary mixture between from the Coordination for the Improvement of Higher Education
FA and Optiphen confirmed some incompatibility phe- Personnel (CAPES), Rio Grande do Norte Research Foundation
nomena. Figure 6 shows the comparison between the theo- (FAPERN) and Pró-Reitoria de Pesquisa (PROPESQ) from Federal
University of Rio Grande do Norte (UFRN).
retical and experimental spectra from the binary mixture that
reviewed three peaks at 1082, 1242 and 1496 cm-1 that are
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