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International Journal of Pharmaceutics 613 (2022) 121370

Contents lists available at ScienceDirect

International Journal of Pharmaceutics


journal homepage: www.elsevier.com/locate/ijpharm

Relationship between sensorial and physical characteristics of topical


creams: A comparative study on effects of excipients
A Ali a, b, c, *, L Skedung d, S Burleigh e, E Lavant a, b, L Ringstad d, CD Anderson f, M Wahlgren e,
J Engblom a, b
a
Biomedical Sciences, Faculty of Health and Society, Malmö University, SE-205 06 Malmö, Sweden
b
Biofilms – Research Center for Biointerfaces, Malmö University, SE-205 06 Malmö, Sweden
c
Speximo AB, Medicon Village, SE-223 81 Lund, Sweden
d
RISE Research Institutes of Sweden, Bioeconomy and Health, Perception and Design, SE-114 28 Stockholm, Sweden
e
Food Technology, Engineering and Nutrition, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden
f
Department of Biomedical and Clinical Sciences, Linköping University, SE-581 83 Linköping, Sweden

A R T I C L E I N F O A B S T R A C T

Keywords: Rising consumer demands for safer, more natural, and sustainable topical products have led to increased interest
Pickering emulsions in finding alternative excipients, while retaining functionality and cosmetic appeal. Particle-stabilized Pickering
Topical creams creams have emerged as possible alternatives to replace traditional surfactant-stabilized creams and are thus one
Tactile friction
of the focuses in this study. The aim of this paper was to study relationships between sensorial characteristics and
Sensory study
Surfactant-free formulations
physical properties to understand how different excipients affect these aspects, comparing one starch parti­
Modified starch cle–stabilized and three surfactant-stabilized formulations. A human panel was used to evaluate sensorial
Rheology perception, while physical properties were deduced by rheology and tactile friction, together with in vivo and ex
vivo skin hydration measurements.
The results show that sensorial attributes related to the application phase can be predicted with rheology,
while afterfeel attributes can be predicted with tactile friction studies. Differences in rheological and sensory
properties among surfactant-based creams could mainly be attributed to the type of emollients used, presence of
thickeners and surfactant composition. Differences between surfactant-based creams and a Pickering cream were
more evident in relation to the afterfeel perception. Presence of starch particles in the residual film on skin results
in high tactile friction and low perception of residual coating, stickiness, greasiness, and slipperiness in sensorial
afterfeel.

1. Introduction delivery as they have good cosmetic properties and are suitable for de­
livery of hydrophobic substances (Marto et al., 2016; Wahlgren et al.,
Development of cosmetically appealing topical formulations is 2013).
important for both the cosmetic and pharmaceutical industry. Topical There is a constant demand for formulators to develop novel safe
drug formulations are used for local treatment of various types of skin formulations of already existing patented drug substances (Wahlgren
disorders but are also interesting for systemic delivery. The main et al., 2013). Formulations need to meet constantly shifting consumer
advantage of topical delivery is avoidance of the hepatic first-pass demands in terms of patient-compliance, cosmetic appeal (Lee and
metabolism, allowing local skin treatment, and decreasing the risks of Maibach, 2006) and rising ethical demands by consumers (e.g. natural
side effects from some drug substances. Emulsions in the form of creams, and sustainable), while still retaining the function intended. New
lotions, gels or foams are the most common formulations for topical formulation prototypes need to be analyzed for functional as well as

Abbreviations: Pickering emulsions, particle-stabilized emulsions; TEWL, trans-epidermal-water-loss; O/W, oil-in-water (emulsions); PC.c, Pickering cream with
carbomer; SC.c, Surfactant-based cream with carbomer; SC, Surfactant-based cream; µS, micro Siemens; a.u, arbitrary units; LVR, linear viscoelastic region; G’,
storage modulus; G’’, loss/viscous modulus; δ, phase angle; F, friction force; L, applied load; µ, friction coefficient; LSD, least-significant-difference; PLS, partial least
squares regression analysis; χ2, Chi-square.
* Corresponding author at: Biomedical Sciences, Faculty of Health and Society, Malmö University, SE-205 06 Malmö, Sweden.
E-mail address: abdullah.ali@mau.se (A. Ali).

https://doi.org/10.1016/j.ijpharm.2021.121370
Received 27 August 2021; Received in revised form 27 November 2021; Accepted 7 December 2021
Available online 21 December 2021
0378-5173/© 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
A. Ali et al. International Journal of Pharmaceutics 613 (2022) 121370

cosmetic properties. systems, little attention has been given to study their sensory and
Functional properties can be studied by physical measurements, cosmetic properties during application and afterfeel. In 2012, Marku
while the cosmetic and sensory properties of topical products are nor­ et al. (Marku et al., 2012) studied the sensorial properties of Pickering
mally evaluated by human panels. Panel-based sensory studies normally emulsions stabilized with quinoa starch with a small human panel. The
require a trained group of panelists or a large consumer panel and can be study reported on the impact of different oil phases but did not discuss
time-consuming and costly. Furthermore, human panels provide sub­ the influence of starch particles. Marto et al. (Marto et al., 2018) later
jective evaluation of the products that is not always beneficial. The use evaluated the cosmetic properties of W/O Pickering emulsions stabilized
of physical methods to screen new formulation prototypes for certain with aluminum starch octenyl succinate with a simple questionnaire.
sensory attributes would be more suitable, allowing for more objective This work did not provide further understanding on the sensorial impact
evaluations and major savings on time and costs. In addition, under­ of starch particles. Recently, a method to study the texture and sensory
standing how specific ingredients affect the physical and cosmetic properties of Pickering emulsions stabilized with inorganic particles was
properties relating to certain sensory attributes would be useful to help developed (Terescenco et al., 2020). These authors focused on sensory
formulators develop products that meet consumer demands. Thus, there analysis of Pickering emulsions stabilized with three types of solid
is a need to find physical methods which correlate with specific sensory particles, solely or in combination with a conventional surfactant,
attributes, and that can distinguish ingredients that cause a certain highlighting the particle effect on the sensory properties of formulations.
perceptible sensation. Several authors have in fact made successful at­ To conclude, none of these studies have conducted a combined approach
tempts to connect physical characteristics of topical formulations to to understand and relate sensorial attributes to physical properties of
certain sensory attributes. Some of the methods that have been linked to starch-stabilized Pickering creams and traditional surfactant-stabilized
sensory attributes are rheology (Greenaway, 2010; Huynh et al., 2021; creams.
Lee et al., 2021; Lukic et al., 2012; Savary et al., 2019; Vergilio et al., In this paper we aim to compare, in a range of different topical
2021), frictional analysis (Lee et al., 2021; Savary et al., 2019; Skedung creams, sensorial perception by a human panel with measurable phys­
et al., 2016; Timm et al., 2012) and texture analysis (Huynh et al., 2021; ical properties of creams using rheology and tactile friction on porcine
Lee et al., 2021; Savary et al., 2019; Vergilio et al., 2021). Rheology was skin, in combination with studying effects on skin hydration. The nov­
found to be a useful tool to predict sensory attributes related to the elty in using porcine skin for tactile friction measurements lies in
application phase of cosmetic emulsions (Lee et al., 2021; Savary et al., allowing real-time recording of touch on skin-skin interaction between
2019), while texture analysis was found to be a good predictor of the fingertip and porcine skin. The objective is to study possible re­
textural attributes comprising stickiness and firmness (Lee et al., 2021; lationships between physical properties and sensorial characteristics
Savary et al., 2019). Some authors also found correlation between and to elucidate the effect of different excipients on the interplay, with
rheological and textural analysis (Gilbert et al., 2013; Lukic et al., 2012; particular emphasis on traditional surfactant-based creams and a starch-
Vergilio et al., 2021). Frictional analysis has been studied to a lesser stabilized Pickering cream. Specifically, we would like to investigate
degree but has been found to be a good predictor for afterfeel attributes how presence of Pickering particles, surfactants, and alternative emol­
(Lee et al., 2021; Savary et al., 2019). Recently, Skedung et al. (Skedung lients affect sensorial properties during application and the afterfeel of
et al., 2016) developed a method to more accurately measure tactile the residual film.
friction of topical formulations by sliding the fingertip on an artificial
skin attached to a friction board (ForceBoard™). 2. Material & methods
The properties of topical formulations can be varied a lot by just
changing the ratio between water and oil. The amount of water in a 2.1. Materials
topical formulation affects both the skin feel during application and the
afterfeel of the formulation on the skin surface as the water evaporates. Modified quinoa starch with 0.5 – 3 µm diameter granules (mean ­
Emollients can vary in molecular and chemical structure affecting their diameter = 1.7 µm), kindly provided by Speximo AB (Lund, Sweden),
melting point, polarity, and viscosity. Emollient type has been shown to was used as stabilizing particles. The starch was hydrophobically
affect skin feel, skin friction, and spreadability of the topical formula­ modified with octenyl succinic anhydride (Timgren et al., 2013). The
tions. Furthermore, emollients can also induce occlusive effects which emollients used were medium chained triglyceride (MCT) (Miglyol 812
hydrate the skin by lowering transepidermal water loss (TEWL) (Gore N, IOI Oleochemical, Hamburg, Germany), isotridecyl isononanoate
et al., 2018; Greenaway, 2010; Nacht et al., 1981; Parente et al., 2005; (Crodamol TN, Croda, East Yorkshire, England), dimethicone (BRB DM
Rawlings et al., 2004; Shai et al., 2009). Humectants are hydrophilic 350, BRB International BV, Thorn, The Netherlands), hydrogenated
compounds with the capacity to retain skin water, thus maintaining coco-glyceride and canola oil (Akosoft 36 and Lipex Preact, AAK, Karl­
hydration and minimizing water loss (Albèr et al., 2013; Lodén M, 2003; shamn, Sweden), jojoba oil (Natura-Tec, Fréjus, France). Liquid paraffin
Tang et al., 2015). The stability of formulations can be improved by oil was purchased from Sigma-Aldrich (Stockholm, Sweden).
addition of rheological modifiers that add body and thickness, and The surfactants used for surfactant-based formulations were cetearyl
cosmetic powders are commonly added to the formulations to improve alcohol (Nafol 1618H, Sasol Performance Chemicals, Hamburg, Ger­
skin feel during and after application (Moussour et al., 2016; Timm many), PEG-100 stearate (Myrj S100), and glyceryl stearate (Cithrol
et al., 2012; Wang et al., 1999). Synthetic surfactants are normally used GMS 40) obtained from Croda Europe (East Yorkshire, England).
to stabilize emulsion droplets, but they could be toxic or irritating Other functional excipients were Carbopol Ultrez 30 (Lubrizol,
especially to patients with sensitive skin (Berardesca et al., 2013; Lu and Brussels, Belgium) (also called carbomer), used as a rheological modifier
Moore, 2012; Veenstra et al., 2009; Wibbertmann et al., 2011). Parti­ and tocopheryl acetate (Dermofeel E74, Evonik Dr Straetmans,
cle–stabilized emulsions, so called Pickering emulsions, have gained a Hamburg, Germany) was used as an antioxidant. Glycerol (Sigma-
lot of interest recently, partially related to the above-mentioned Aldrich, Stockholm, Sweden) was used as a humectant and the pre­
formulation demands such as producing a mild surfactant-free prod­ servatives used were phenoxyethanol and caprylyl glycol (Versatil PC,
uct, and the possibility to use natural ingredients, and create new tex­ Evonik Dr Straetmans, Hamburg, Germany), propyl–4–hydroxybenzoate
tures. But the main interest in Pickering emulsions is related to the fact (Propyl paraben, Solbrol P) and methyl-4-hydroxybenzoate (Methyl
that these emulsions can have high long-term stability towards coales­ paraben, Solbrol M) were provided by Lanxess GmbH (Leverkusen,
cence and Ostwald ripening (Albert et al., 2019; Aveyard et al., 2003; Germany). Milli-Q water, 18.2 MΩ cm resistivity, was used for all
Binks, 2002; Sjöö et al., 2015; Timgren et al., 2013; Venkataramani samples.
et al., 2020). While much of the work published on Pickering emulsions
focuses on studying the stability and functional properties of such

2
A. Ali et al. International Journal of Pharmaceutics 613 (2022) 121370

2.2. Formulations − 80 ◦ C. The ears were residuals from food preparation. No pigs were
sacrificed for the purpose of this study, hence ethical permission was not
All the formulations studied in this work were oil-in-water (O/W) required. To prepare the skin substrate, thawed pig ears were cleaned,
emulsions. A commercial surfactant–based pharmaceutical cream was and hair was removed with a trimmer. Full–thickness skin was excised
included (Canoderm®) for comparison, purchased from a local phar­ from the inner ear using a scalpel and cut into strips (2 × 5 cm2). Finally,
macy in Sweden. The creams prepared in the lab (batch size ~ 100 g) the excised porcine skin was wrapped in aluminum foil and stored in
were a surfactant-free Pickering cream with carbomer (PC.c), a – 20 ◦ C until use. Before conducting tactile friction measurements, the
surfactant-based cream (SC.c) with carbomer as thickener and equiva­ skin was allowed to thaw and equilibrate at room temperature at least 1
lent composition to PC.c, and a surfactant-based cream (SC) without a h) with a hydrated filter paper underneath. Skin from different porcine
thickener and with a different emollient composition. The compositions ears and position on the ear was randomized among the measurements.
of the cream formulations are given in Table 1.
The PC.c was prepared by mixing the water-soluble and oil–soluble
2.4. Sensory evaluation
excipients separately. The oil phase was heated to 60 ◦ C until all
emollients were melted, and the temperature was brought down to <
Sensory perception evaluation was carried out on the four moistur­
45 ◦ C. The starch was added to the water phase below 45 ◦ C, during
izing cream formulations (PC.c, SC.c, SC and Canoderm®) for percep­
mixing with a propeller stirrer (IKA RW-20, IKA, Germany), mixed for
tional attributes during application and afterfeel. Thirty–one healthy
additional 5–10 min before slowly adding the oil-phase with stirring.
untrained volunteers (19 females, 12 men), with no history of skin dis­
The mixture was stirred for an additional 5–10 min before emulsifica­
ease, were recruited among students and university personnel at the
tion with a high shear mixer (IKA Ultra Turrax T25, IKA, Germany) at
Faculty of Health and Society (Malmö University) to participate as as­
15000 rpm for 1 min in a glass beaker.
sessors in the study in accordance with ISO 8586:2012. The age ranged
The SC and SC.c formulations were prepared in a similar way, where
between 18 and 64, whilst most participants were in the age range
the oil-phase and water–phase were mixed separately at 65–75 ◦ C until
25–34 (67.7%). Ethical approval was received by the Swedish Ethical
all ingredients were dissolved, before adding the oil-phase to the water-
Review Agency (DNR 2019–05452) to conduct the study, and informed
phase while mixing with a propeller stirrer. The mixture was stirred for
consent was obtained by all volunteers.
5 min before emulsification with a high shear mixer at 12000 rpm for
The evaluations were performed with assessors seated in individual
1–2 min and allowed to cool down to room temperature during mixing.
booths with partition walls and homogenous artificial lightning in a
dedicated room isolated from external disturbances, with temperature
2.3. Preparation of skin substrates and humidity control in accordance with ISO 8589:2007. The study was
divided into sessions of 4–6 assessors per session. Prior to each session,
Fresh porcine ears were acquired from a local abattoir and stored at the assessors were asked to wash and dry their hands and were

Table 1
Composition of investigated cream formulations in (wt%).
Pickering Surfactant-based replica of Surfactant-based Surfactant-based
cream Pickering cream cream commercial cream
Description Functional category

Cream id PC.c SC.c SC Canoderm® *

Water Solvent to 100.0 to 100.0 to 100.0 Y


Glycerol 5.0 5.0 – –
Urea Humectants1,2 – – – Y
Propylene glycol – – – Y
Glyceryl polymethacrylate Film-forming1 – – – Y
Carbomer Rheology modifier 0.10 0.10 – Y
Modified Quinoa starch Stabilizing particles 10.0 – – –
PEG-100 stearate – 2.0 2.0 Y
Glyceryl stearate Surfactants / emulsifiers1 – 2.0 2.0 –
Cetearyl alcohol – 2.0 2.0 Y
Polysorbate 60 – – – Y
MCT-oil** 12.0 12.0 – Y
Isotridecyl Isonnanoate 4.0 4.0 – –
Canola oil 4.5 4.5 – Y
Hydrogenated Emollients 3.0 3.0 – –
Coco–glycerides
Jojoba-oil 3.0 3.0 – –
Solid paraffin – – – Y
Liquid paraffin oil – – 15.0 –
Dimethicone – – 15.0 Y
Tocopheryl acetate Antioxidant2 0.50 0.50 – –
Phenoxyethanol/Caprylyl – – 0.70 –
glycol
Ethyl paraben Preservatives1 – – – Y
Propyl paraben 0.20 0.20 – –
Methyl paraben 0.20 0.20 – Y
Buffering, water–binding2
Lactic acid /skin–conditioning1 – – – Y
Citric acid Buffering1 – – – Y

* Composition according to ingredient list on product. Y = yes.


** MCT = medium chain triglyceride.
1
(Rowe et al., 2013).
2
(Lodén, 2005).

3
A. Ali et al. International Journal of Pharmaceutics 613 (2022) 121370

introduced to the test procedure and the terminologies by the project Table 2
leader. The introduction allowed for an automatic 20–30 min quiet The attributes evaluated using a ranking test, given in the order they were
acclimation period for the assessors. The assessors had been further evaluated in the study with definitions and instructions as specified in the sur­
asked to avoid caffeine beverages 3 h before the session, not to cover vey. 50 µl of each formulation was applied on circular sites on the volar forearms
their forearms, and not to apply any topical formulation 12 h prior to the (two sites per forearm).
session in accordance with guidelines for in vivo measurements on skin Attributes, Definition Instructions
(Berardesca et al., 2018; Otto et al., 2009; Pinnagoda et al., 1990). Application
phase
Each sample was assigned a random three-digit code and presented
in an identical dark glass container. The order of presentation was Moistness The amount of liquid Spread the sample droplet within
(wetness) which can be the marked circle in a circular
balanced by randomized complete block design to avoid first order and/
perceived during application motion with 1 finger. (1 circle/
or carry-over effects within sensory sessions. The sensory attributes were second).
assessed on two defined circular measurement sites (d = 4 cm) on each After 3 circulations, evaluate how
volar forearm, placed 7 cm from the wrist and elbow, and distanced 2 cm moist the samples are.
from each other. Each circle was labelled with a sticker with the
Spreadability The ease to spread the Continue distributing the sample
formulation 3-digit code according to the randomized order. The as­
sample over a larger skin on the skin in circular motion (1
sessors were given similar labels on the back of their fingers, as a area circle/second).
reminder to use one finger for each measurement site to avoid carry-over After another 2 circulations (total
effects and confusion. 5), evaluate how spreadable the
samples are.
In vivo baseline measurements of skin hydration for each measure­
ment site were taken prior to application of 50 µl of each cream by the Thickness The amount of sample-film Continue distributing the sample
project leader to the middle of the circular measurement sites using a between the finger and the in a circular motion (1 circle/
M1000 positive displacement pipette (Microman®, Gilson, France). skin second).
Once the creams were applied, assessors were allowed to start the After another 7 circulations (total
12), evaluate the thickness of the
evaluation following the instructions on a digital survey (Microsoft ­
samples.
Forms) on a tablet computer. The study was divided between attributes
evaluated during the application phase, and attributes evaluated in the Absorption How fast the sample absorbs Continue distributing the sample
afterfeel phase when volatile compounds have evaporated (11 min after into your skin in a circular motion (1 circle/
second). Max 18 additional
application). The sensory attributes evaluated, and instructions are
circulations (total max 30)
summarized in Table 2. After evaluating the attributes during applica­ Evaluate how fast the sample is
tion, the assessors were asked to clean their fingers with facial tissues absorbed by your skin.
and answer a questionnaire with background information during the
Attributes, Definition Instructions
waiting time before the afterfeel evaluation phase. The creams were Afterfeel
ranked for each attribute according to the rank test (ISO 8586:2006) phase
(Meilgaard et al., 2016; Whelan, 2017), rank ordering the four formu­ Stickiness How sticky/gluey the skin Press your finger withing the
lations from 1 to 4 for the highest to lowest perception for each specific feels marked circle and lift it to
attribute. After ranking the formulations, the assessors could choose evaluate the stickiness. You may
their preferred cream formulation for each studied attribute. They were repeat it 3 times.
Evaluate how Sticky the skin area
also asked to choose their overall preferred formulation during the feels.
application phase and between the creams overall. By the end of the
study, the assessors were also asked to describe each formulation by Residual The amount of remaining Use your finger to slide softly over
choosing words from a word cloud, or by using their own words. Coating product on the skin area the skin in the marked circles and
evaluate how much product that
remains.
2.5. Skin hydration measurements
Greasiness Amount of oil/fat which can Slide your finger within the
Skin hydration was measured in vivo during the sensory perception be perceived on the skin marked circles and evaluate how
study before the application of creams, and upon completion of the surface greasy/oily the skin area feels.
Slipperiness How slippery the skin feels Let your finger slide over the skin
study by electrical conductance by means of a hydration probe (Der­
in the marked circles and evaluate
malab, Cortex Technology, Denmark) at circular measurement sites on how slippery the area feels.
the volar forearms. The instrument measures skin conductance at a
single frequency, 300 kHz, which can be related to the water content of Softness How soft and smooth the Let the finger slide slowly in the
skin feels marked circles and evaluate how
stratum corneum on an arbitrary scale (Morin et al., 2020). The results
soft the area feels.
are given as the relative change (%) in µS (microSiemens) on each
measurement site to evaluate the effect of the formulations on skin
hydration. 2.6. Rheological studies
Ex vivo skin hydration measurements were performed during tactile
friction measurements, using a Corneometer (CM825, Courage Khazaka Rheological measurements were performed using a stress-controlled
Electronic GmbH). The principles for the instrument are based on rheometer, Bohlin CVO100 (Malvern Instruments, UK) equipped with a
capacitance measurement and it was used to measure the skin hydration parallel plate with a diameter of 25 mm and a gap size of 0.50 mm. The
of the finger and the excised skin, prior to each experiment. A second formulations were applied to the bottom plate with a stainless–steel
measurement was performed after each experiment on the excised skin. spatula and analyzed at 32 ◦ C. Continuous flow tests (hysteresis loop
The results are given as the relative change (%) in arbitrary units (a.u) tests) of the formulations were carried out with shear rate ramp, by
on excised skin to evaluate the effect of skin hydration on friction increasing the shear rate from 0.25 to 200 s− 1, hold time of 0.1 s, and
results. decreasing to 0.25 s− 1. The duration of each step was 10 s. The steady
shear viscosity and hysteresis loop area values were calculated from the
obtained curves (shear stress vs shear rate) using the Bohlin Rheometer

4
A. Ali et al. International Journal of Pharmaceutics 613 (2022) 121370

Software. Dynamic (oscillatory) tests were performed to determine the Multivariate analysis was carried out using Matlab (v. R2020b).
linear viscoelastic region (LVR) and yield stress of the samples, at con­ Linear partial least squares regression analysis (PLS) was used to visu­
stant frequency of 1 Hz and an amplitude sweep ramp from 0.24 to 1000 alize the relationships between the studied creams, the rank sums of the
Pa. A frequency sweep was performed in the linear region from 0.1 to sensory attributes and the mean data for the physical measurements.
1000 Hz at 0.3 Pa constant shear stress. The storage (G’) and loss (G”)
moduli phase angle (δ) was measured. The yield stress was determined 3. Results
from the onset value of the modulus curves in a double logarithmic plot
of the storage modulus as a function of oscillation stress (Dinkgreve 3.1. Participants’ background
et al., 2016; Walls et al., 2003).
Questionnaire results provided background information about the
2.7. Tactile friction measurements participants in the sensory perception study (Appendix A, supplemen­
tary information). Most of the participants were females (61%), and a
Tactile friction measurements were performed using a ForceBoard™ large number of the participants were in the age range 25–34 years old
(Industrial Dynamics Sweden AB, Järfälla, Sweden), following the (67%). Almost half of the participants (48%) use hand cream on a daily
method described by Skedung et al. (Skedung et al., 2016) with minor basis, while the rest use it only on a weekly basis (19%), seasonally
adjustments. The instrument is equipped with both a horizontal and one (19%), or never (4%).
tangential load cell, consisting of strain gauges in a Wheatstone bridge Most of the participants preferred non-greasy (>38%) and soft,
configuration. A mechanical load results in voltage changes that are cushioning (>38%) moisturizing creams. Some participants (15%)
proportional to the applied load. A temperature-controlled plate was preferred their moisturizing creams to be thin as well as non–greasy/
placed on top of the ForceBoard™ (32 ◦ C) and excised porcine skin (2x5 soft, cushioning. Upon ranking the most important criteria when pur­
cm2) was mounted on the heated plate with hydrated filter paper un­ chasing a new moisturizing cream, the top three criteria most important
derneath. The friction force (F) and applied load (L) were continuously for the participants were the moisturizing effect, the afterfeel sensation,
recorded as a finger interrogated the model skin surface by moving the and texture. Based on this information we can conclude that the afterfeel
index finger back and forth, and the friction coefficients (µ) were sensation of the applied formulation is important for the participants in
calculated as a ratio of the friction force and load according to: this study, and that a cream with a moisturizing effect and a non-greasy
and soft afterfeel is more likely to be preferred.
F
μ= (1)
L
3.2. Sensory perception evaluation
Approximately 4–5 mg cm− 2 of the topical formulations (PC.c, SC,
and Canoderm®) were applied to the skin substrate. For each experi­ The results of the sensory study (Table 3) show statistically signifi­
ment the index finger, inclined 30◦ , was stroked forward and back 10 cant differences (p < 0.05) in participant’s ranked preference between
times to spread 50 µl (20–25 mg) of applied formulation over the sample the four cream formulations for all sensory attributes except thickness
area (4–5 cm2). A control measurement on untreated skin substrate with and absorption. The rank sums of the cream formulations for each
10 S was performed prior to each measurement as control for changes in sensorial attribute are illustrated in a radar chart in Fig. 1A.
skin and finger. The friction was measured for 30 s during application of
the formulation at the time points 2.5 min, 5.5 min, and 11 min after 3.2.1. Perception during the application phase
application. All experiments were performed in controlled ambient The attributes evaluated during the application phase are relevant to
conditions (temperature = 21 ◦ C ± 0.3 ◦ C, relative humidity = 49% ± the cosmetic appeal of creams, and formulations ranked high for these
6%) by the same experimenter. The method was validated by compar­ attributes are generally considered as cosmetically appealing for con­
ison with another experimenter and an artificial skin substrate (un­ sumers. Moistness, and absorption are related to the sensation of the skin
published results). The friction force and the applied load were recorded being moisturized and hydrated, while thickness and spreadability are
with a sampling rate of 100 Hz and the applied load was maintained related to a pleasant feeling and the ease of application. During the
around 0.5 N. The results are given as average friction coefficient values application of the topical creams to the skin, the formulations need to
normalized against corresponding values for the untreated skin sub­ spread easily without feeling too greasy or sticky (Kwak et al., 2015;
strates to control for biological variation between individual skin sub­ Vergilio et al., 2021). Formulations ranked high for these attributes can
strates. The results for untreated skin substrates show a small reduction be considered as cosmetically appealing for consumers.
in normalized friction coefficient over the measurement period of 11 During the application phase, Canoderm® was perceived as less
min, tentatively resulting from water evaporation with time (unpub­
lished results). Table 3
For each sensory attribute, Chi-square values (χ2), and p-values from Friedman’s
2.8. Statistical analysis test and rank sums for the cream samples with multiple comparisons using
Fisher’s least-significant-difference (LSD, p < 0.05). High rank sums correspond
Whenever applicable, results were expressed as averages ± standard to high level of perception for each sensory attribute.
deviation, and differences between cream formulations were deter­ Attributes χ2 p-value PC.c1 SC.c2 SC3 Canoderm®
mined by one-way ANOVA with Tukey’s HSD test. Statistical outliers Moistness 9.62 0.022* 76 ab
81b 92b 61a
were excluded based on two-sided Grubbs’ test (p < 0.05). Spreadability 19.26 <0.001* 66a 92b 94b 58a
A Friedman test of difference was used to determine whether par­ Thickness 4.74 0.192 67a 86a 73a 84a
ticipants had a significant different rank ordered preference for the four Absorption 6.60 0.086 73a 66a 91a 80a
Stickiness 32.26 44a 78b 94b 94b
cream formulations (p < 0.05). The Friedman test is the non-parametric <0.001*
Residual Coating 10.08 0.017* 62a 94b 75ab 77ab
alternative to the one-way ANOVA and shows whether significant dif­ Greasiness 16.59 <0.001* 55a 96b 79b 80b
ferences exist between two or more samples that are ranked by all Slipperiness 35.05 <0.001* 45a 101c 73b 91c
panelists. It is a very sensitive test to find a pattern of consistent rank Softness 31.68 <0.001* 46a 87bc 76b 101c
order (Lawless and Heymann, 2010). Whenever there was a significant *
for significant results, p < 0.05. Creams sharing the same significance group
difference, pairwise comparison was performed using Fisher’s letter (a,b, c) show no difference in ranked perception. 1PC.c = Pickering cream
least–significant–difference (LSD) test to determine which of the cream with carbomer. 2SC.c = Surfactant-based cream with carbomer. 3SC = Surfac­
formulations was significantly different (p < 0.05). tant-based cream.

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A. Ali et al. International Journal of Pharmaceutics 613 (2022) 121370

Fig. 1. Radar charts of rank sums (A) and preference score (B) of each cream formulation for the studied sensory attributes. Sensory attributes studied during the
afterfeel phase are star marked. A: Rank sums of each cream formulation for the studied attributes. A higher value of rank sums for a certain sensorial attribute means
a stronger perceived intensity for this attribute for a given formulation (e.g., most soft). B: Preference score of each cream formulation for the studied attributes,
showing which cream was most preferred for a specific attribute. The formulations were Pickering cream (PC.c) in green, surfactant-based cream replica of Pickering
cream (SC.c) in blue, surfactant-based cream (SC) in yellow, and surfactant-based commercial cream (Canoderm®) in purple.

moist than SC.c and SC (p < 0.05), and together with PC.c it was greasiness. SC was the overall most preferred cream for the application
perceived as less spreadable than SC.c and SC (p < 0.05). The highest attributes. When asked for the most preferred cream overall, without
rank sums overall for the sensory attributes during the application phase thinking of a certain attribute, Canoderm® was the most preferred
were given to SC for all sensory attributes except thickness, where SC.c cream. Canoderm® is a fully developed product and marketed as an
and Canoderm® were higher. Thus, we can conclude that SC was efficient moisturizer, in comparison to the prototypes prepared in the
perceived as the moistest, the easiest to spread, and the cream to absorb lab, and this difference was perceived by the assessors when they only
fastest by the skin during the application phase. needed to compare the overall performance between all four creams.
The preference results differed to some extent from the results by
3.2.2. Perception during the afterfeel phase ranking. This highlights how the participants are in different state of
According to the human panel in this study, the afterfeel sensation is mind when asked to compare and rank the creams based on level of
an important criterion when purchasing a cream. Most participants perception for each attribute, and when asked to choose the cream they
preferred a non-greasy and/or soft afterfeel. Thus, a high rank sum value preferred the most. In the first case, they are in an analytical frame of
for softness and a low value of rank sums for greasiness can be inter­ mind when comparing and ranking, while they are looking at the cream
preted as being cosmetically appealing for this specific panel. In general, as a whole and judging based on their own preferences when asked to
some of the attributes related to the afterfeel phase are commonly choose the most preferred (Lawless and Heymann, 2010). Preference
considered unfavorable; such as stickiness, greasiness and slipperiness tests would require a larger number of assessors or trained panelists and
(Kwak et al., 2015; Lodén M, 2003; Nacht et al., 1981; Savary et al., preference results were only considered as supplement to the rank test.
2019), while softness can be seen as a favorable attribute, e.g., a pow­
dery afterfeel (Moussour et al., 2016; Timm et al., 2012). Low values of 3.2.4. Participants’ descriptive words
rank sums for stickiness, and slipperiness can also be considered as At the end of the sensory study, the participants were asked to
cosmetically appealing. describe each cream formulation with their own words. A word cloud
In the afterfeel phase, 11 min after the formulations were applied, animation was provided as assistance. The words used to describe each
the participants’ ranked preferences showed that the lowest rank sums cream formulation are illustrated in Fig. 2, with colors and font size
(p < 0.05) were given to PC.c for all afterfeel sensory attributes. The highlighting how frequent each word was used. The words that where
afterfeel of PC.c was thus perceived as the cream with least stickiness, used the most to describe PC.c were “grainy” and “easily absorbed”,
greasiness, residual coating, slipperiness but also the least soft. Can­ while SC.c was described as “greasy” and “oily”. Canoderm® was
oderm®, SC and SC.c were perceived as sticky and greasy in afterfeel, described as “smooth”, “soft”, and “greasy” and SC was described as
with high rank sums for stickiness and greasiness. The highest amount of “soft”, “natural” and “oily”.
residual coating was perceived for SC.c in the afterfeel phase, signifi­ The most common words used to describe all three surfactant-based
cantly different from PC.c (p < 0.05). Furthermore, the residual films of creams SC, SC.c and Canoderm® were “soft”, “greasy”, “oily”, and
SC.c and Canoderm® were perceived as most slippery on skin, signifi­ “smooth”. These words were either not used at all or less frequently used
cantly higher than PC.c and SC (p < 0.05) separately, and the cream that to describe the surfactant-free PC.c. Soft and smooth relates the sensa­
was perceived to leave the softest (p < 0.05) skin sensation in the end tion of the formulation film, while greasy and oily relates to the amount
was Canoderm®. of residual oil film perceived after application. The words that were
frequently and solely used to describe PC.c besides “grainy” and “easily
3.2.3. Preference choice absorbed” were “powdery feeling”, “dry”, “dry residue”, “rough”,
The assessors were also asked to choose the cream they preferred the “matte”, and “bad quality”. Most of these words indicate that the par­
most for each attribute during application and afterfeel phases, Fig. 1B. ticipants could feel the presence of starch particles either as a result of
During the application phase, SC.c, was preferred the most for moistness dry afterfeel or as powdery, rough, matte feeling and that some of these
and spreadability attributes while Canoderm® was the most preferred sensations were associated with “bad quality” for some of the assessors.
cream for thickness and absorption attributes. For the afterfeel attri­ Surfactant-based creams can be perceived as soft and smooth, while
butes, Canoderm® was the most preferred for softness and slipperiness resulting in a greasy and oily afterfeel. In contrast, a surfactant-free
while SC was most preferred for stickiness, residual coating, and Pickering cream is perceived as grainy but with a dry, powdery

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A. Ali et al. International Journal of Pharmaceutics 613 (2022) 121370

Fig. 2. Word clouds of the words used to describe each cream formulation. Difference in frequency of used word is highlighted by colors and font size (larger size for
higher frequency).

afterfeel. These results highlight the impact of the presence of starch


particles in the residual film on the perception of greasiness, stickiness,
and oiliness. However, the large diversity of words used to describe each
cream indicate that it was difficult to describe the overall skin feel of
each cream. It is also important to keep in mind that the panel consisted
of untrained subjects and the individual expectations and preferences
may impact how the creams are perceived. We can conclude that there is
a difference in how participants perceived traditional surfactant–based
creams and the surfactant-free Pickering cream.

3.2.5. Hydration measurements in vivo


The results of the hydration measurement (Fig. 3) of the skin before
and after the application of creams can help distinguish the degree of
hydration to the skin after application of the creams. The relative change
(%) in µS was significantly highest for Canoderm® (p < 0.05), followed
by SC.c. Even though SC.c and PC.c have the same composition of ex­
cipients and differ only by the addition of starch particles instead of Fig. 3. Relative change in conductance, μS, after application of cream formu­
surfactants, the relative change in skin hydration was significantly lations in vivo. Results are expressed as average (n = 30) and error presented as
higher for SC.c (p < 0.05). The fatty and hydrophobic composition of the standard deviation, and differences between cream formulations were deter­
surfactants can contribute to an occluding effect giving rise to a higher mined by one-way ANOVA with Tukey’s HSD test. Creams with different group
value in skin hydration, while the presence of starch particles may alter letter (a, b, c, d) are significantly different (p < 0.05) in relative change
in hydration.
the occluding properties of the residual oil film.
The difference between the surfactant-based creams could be related
to difference in oil composition and presence of humectants. Further­ 3.3. Rheological studies
more, Canoderm® is marketed as an efficient moisturizer with 5% urea
as well as propylene glycol as humectants, compared to glycerol which is 3.3.1. Flow curves
present in PC.c and SC.c. Urea has been shown to be an efficient hu­ The flow properties of a cream can tell us how easy it is to apply and
mectant to increase skin hydration (Albèr et al., 2013), resulting in spread a cream on the skin. It has been suggested that a skin cream
lower TEWL in comparison to glycerol (Lodén et al., 2001). Hence, should have low viscosity at high shear to be easy to apply, and high
addition and choice of humectants together with occlusive emollients viscosity at low shear so it does not spill out of the container (Green­
significantly affect the moisturizing properties of a cream. away, 2010). The flow behavior of the studied creams (Fig. 4) show that
all creams exhibited shear-thinning and thixotropic behavior. It can be

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A. Ali et al. International Journal of Pharmaceutics 613 (2022) 121370

et al., 2015). Therefore, it is not surprising that formulations including


carbopol displayed higher yield stress and viscosity. However, differ­
ences beyond the addition of carbopol could relate to the amount or type
of oil used and the microstructure of the oil droplets. According to
Brummer et al. (Brummer and Godersky, 1999) the onset of flow for
creams is above a critical shear stress of 10 Pa, whereas lotions begin to
flow at lower yield stresses < 10 Pa. The four main formulations
investigated here all displayed yield stress values above 10 Pa indicating
that they are suitable as topical creams.
A frequency sweep was performed for all formulation at a value of
shear stress within the LVR at 0.3 Pa (Table 4). The values of G’ were
higher than G’’ (tan δ < 1) for all the formulations in a wide frequency
range (up to 10 Hz), indicating elastic behavior and that all samples are
in a gel (or solid) state. Above 10–29 Hz, the G” crosses over and be­
comes higher than G’ (tan δ > 1) showing that viscous behavior starts to
dominate, and the samples enter into a liquid state. The values of tan δ
(G’/G”) were lowest for PC.c, which suggest that it is the most elastic
sample with sturdier internal structure.

Fig. 4. Shear-thinning behaviour for all formulations. Pickering cream (PC.c), 3.4. Tactile friction
green circles, surfactant-based Pickering cream replica (SC.c), blue triangles,
surfactant-based cream (SC), yellow diamonds, and surfactant-based commer­
During initial application of a cream, when the film formed between
cial cream (Canoderm®), purple squares.
skin and finger is rather thick, the friction is highly affected by the
viscosity of the formulation, and the friction properties are related to the
noted that steady shear viscosity (at low shear rate) was highest for
perceived slipperiness of the product (Guest et al., 2013; Skedung et al.,
Canoderm® and PC.c, followed by SC.c and SC. The creams with higher
2016; Tang et al., 2015). After spreading of the formulation, as the water
viscosity all had in common the presence of a structural thickener
and other volatile components evaporate, the effect of the product on
(carbomer). The presence of starch in the PC.c could explain the higher
the skin can be detected. For example, hydrated and soft skin gives rise
initial viscosity of PC.c in comparison to SC.c. SC exhibited the lowest
to a higher friction, while a large amount of non–adsorbed oil residue on
shear viscosity and differed the most from the other creams.
the skin may give rise to lower friction (Nacht et al., 1981; Skedung
et al., 2016; Tang et al., 2015).
3.3.2. Oscillation measurements
The average normalized friction coefficients during application on
Yield stress is a measure of the stress required to induce flow in a
skin, and 2.5, 5.5 and 11 min after application of studied cream for­
product and can be related to the interparticle structure. Results from
mulations are shown in Fig. 5. Upon application (0 min), there is an
oscillation amplitude sweep measurements are shown in Table 4.
initial drop in friction of the skin due to spreading for all the creams in
All formulations showed elastic behavior at low stress, indicated by
comparison to the untreated skin samples. Once the thickness of the
higher G’ values than G” values, and displayed a LVR up to approxi­
formulation film is decreased and subsequent changes of the residual
mately 3 Pa. Upon further increase of the shear stress, the G’ values drop
film occur, including the evaporation of volatile compounds, the
for some formulations and the viscous flow effects is apparent with G’’
normalized friction is increased for all formulations. PC.c shows a pro­
leading to cross over. Yield stress results were determined from the onset
nounced increase in friction after 2.5 min, and by the end of the
of the curve of G’ (Dinkgreve et al., 2016) (Figure A1, Appendix A) and
experiment (11 min), the friction of PC.c is still higher than untreated
summarized in Table 3. The highest yield stress recorded was 129.7 Pa
skin. Canoderm®, SC.c and SC displayed a minor gradual increase in
for Canoderm®. PC.c exhibited lower yield stress (77.8 Pa) than Can­
friction over the measuring time. After 11 min, Canoderm® reaches
oderm® but higher than SC.c (33.2 Pa). The difference between PC.c and
similar friction levels as untreated skin, while the friction for SC.c and SC
SC.c can be attributed to the difference in using surfactants or starch
(SC.c > SC) is lower than that of untreated skin. The difference in fric­
particles as emulsion stabilizers and the difference in microstructure.
tion between Pickering-stabilized (PC.c) and surfactant-stabilized
The lower yield stress of SC.c indicates increased breakdown of the
creams (SC.c, SC, and Canoderm®) can be related to the use of starch
structure in comparison to PC.c. The only cream which did not include
particles instead of surfactants. The residual film in Canoderm®, SC.c
any structural thickener was SC, and it exhibited the lowest yield stress
and SC contains oils and surfactant residues which could contribute to
values (<16.8 Pa).
more slippery and greasy tactile properties reducing the friction. As for
Carbopol as a structural thickener is known to enhance stability, and
PC.c, the residual film contains mainly oils and starch particles, where
add body to skin cream samples (Epstein, 2009; Greenaway, 2010; Kwak
the presence of starch particles may contribute to higher tactile friction

Table 4
Rheological parameters of investigated formulations. G’, G”, and phase angle values were obtained at 1 Hz. Yield stress was obtained from the onset of the curve of G’.
Steady state viscosities and hysteresis loop areas were obtained from flow tests. Values are given as mean ± SD.
Creams Temp.(◦ C) Hysteresis Steady shear viscosity G’ (Pa) G’’ (Pa) Tan δ Yield Stress (Pa)
Loop area (Pa s− 1) (Pa s)

Canoderm® 32 4913 ± 423 460.8 ± 68.6 6181 ± 1276 3287 ± 1534 0.51 ± 0.1 129.7
PC.c1 32 288.7 ± 50.3 871 ± 178 69.2 ± 7.5 0.08 ± 0.02 77.8
2846 ± 417
SC.c2 32 105.4 ± 20.3 1277 ± 115 359 ± 86 0.28 ± 0.04 33.2
3171 ± 37
3
SC 32 28.5 ± 5.9 619 ± 201 229 ± 71.1 0.37 ± 0.01 16.8
1875 ± 15
1
PC.c = Pickering cream with carbomer. 2SC.c = Surfactant-based cream with carbomer. 3SC = Surfactant-based cream.

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A. Ali et al. International Journal of Pharmaceutics 613 (2022) 121370

Fig. 5. Tactile friction results on excised skin at 32 ◦ C of the studied formulations. Surfactant-based cream (SC) in yellow, surfactant-based commercial cream
Canoderm® in purple, surfactant-based cream with carbomer (SC.c) in blue, and Pickering cream (PC.c) in green. One-way ANOVA showed that the SC and PC
difference at 2.5 min and 5.5 min is statistically significant (p < 0.10).

and counteract the reduction in friction caused by the residual oil. Nacht observed for all creams except SC, but no significant differences in hy­
et al. (Nacht et al., 1981) concluded that greasy products have been dration were found among the creams and untreated skin. The increase
found to induce an initial decrease in friction coefficient, while products in hydration was highest for Canoderm® followed by PC.c and SC.c.
that increase friction coefficients would be perceived as non-greasy. Canoderm® comprises humectants such as urea and propylene glycol
Thus, high friction inducing PC.c can be considered as non-greasy, which may have contributed to the higher skin hydration in combina­
while surfactant-based creams with lower friction can be perceived as tion with occlusive effects of the emollient composition. PC.c and SC.c
greasy. Timm et al. showed that adding particles to an aqueous sus­ both comprised glycerol as humectant, and although starch particles in
pension lowered friction and friction lowering was particle size depen­ PC.c may alter the properties of the occlusive film, the skin hydration for
dent (Timm et al., 2012). However, no comparisons were made with PC.c was still higher than SC.c. SC did not include any humectants and
emollients or particle containing creams. It is thus not farfetched to contained different emollient composition which may have contributed
assume that, once water evaporates from the formulation, the friction to the lower skin hydration. Thus, humectants when combined with an
would differ between a dry particle residue after an aqueous suspension, appropriate occlusive emollient composition had a larger impact on skin
and a reside of particles and oil mixed after an emollient suspension or a hydration results. The higher skin hydration levels of Canoderm® may
cream containing particles. Furthermore, the microstructure of the re­ explain the difference in friction results between Canoderm®, SC.c and
sidual film may also differ for particles dispersed in a surfactant-based SC, since hydrated skin increases friction. Canoderm® was also the
cream, or particles used as emulsifiers surrounding the oil droplets cream that increased the participants skin hydration the most in vivo.
(Pickering emulsions). Difference among surfactant-based creams (SC.c,
SC and Canoderm®) may be attributed to the different properties of the 4. Discussion
residual film due to different emollient and surfactant composition, as
well as presence of thickeners. 4.1. Relationship between sensory and physical data and creams

3.5. Hydration measurements ex vivo In this study we have conducted a study comprising both sensory
properties and physical chemical properties of a Pickering-stabilized
The relative change (%) in skin hydration (a.u) of excised skin before cream and three surfactant-stabilized creams. Sensory properties are
and after the experiment for the different treatments is shown in Fig. 6. always the key attribute from a consumer perspective, but consumer
For untreated skin samples, a reduction in skin hydration (up to 27%) panels are time consuming and thus not a fast tool during the develop­
was noted for the experiment period of 11 min. Thus, the water loss from ment phase. Consequently, there is a need to link the sensory properties
the hydrated excised skin due to evaporation was high. There was ten­ to easily measurable physical properties.
dency for relative increase in hydration 11 min after application We conducted partial least square (PLS) mainly as a visual tool (due
to limited numbers of studied creams) to study the relationships be­
tween physical data, sensory data, and the studied creams. Sensory data
comprised rank sums of the creams for each sensorial attribute evaluated
by thirty-one assessors, and the physical data comprised average data of
replicates (n = 3–4) for each cream and physical parameter. PLS showed
that the main data variance, 62.46%, was explained by the first two
principal components. The first principal component (PC1) explained
38.07% of the data variance, while the second principal component
(PC2) accounted for 24.39% of the variance. A PLS plot combining the
sensory data, physical data, and the studied creams (Fig. 7) suggests that
PC1 is associated with afterfeel attributes and physical data, since they
are generally distributed along the x-axis. Tactile friction data and
ex vivo hydration data are positioned on the positive side of the x-axis
and rheological and in vivo hydration data are, in general, on the
Fig. 6. Change in a.u % after application of formulations on excised skin (11 negative side of the x-axis. PC2 seems to be associated with sensory
min). Surfactant-based cream (SC), yellow bar, commercial cream Canoderm®, attributes related to the application phase, due to their apparent dis­
purple bar, surfactant-based cream with carbomer (SC.c), blue bar, Pickering tribution along the y-axis. In general, it seems as if PC2 shows differ­
cream (PC.c), green bar, and untreated skin substrates, textured bar. Errors are ences between moist and thin creams and fatty and thick creams.
presented as standard deviations. The four studied creams were distributed quite well in both

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A. Ali et al. International Journal of Pharmaceutics 613 (2022) 121370

Fig. 7. Partial least square (PLS) visualizing the relationships between sensory data (circles), physical data (black stars) and studied creams. Sensory data are shown
as attributes studied during the application phases (white circles) and during the afterfeel phase (black circles). The studied creams are Pickering-stabilized PC.c
(green circle) and surfactant-stabilized creams SC (yellow diamond), SC.c (blue triangle), and Canoderm® (purple square).

dimensions of the PLS, indicating that each cream appears to have tactile friction data in general. Spreadability seems to be negatively
unique characteristics in their perceived attributes. Pickering-stabilized associated with friction results at 2.5 min, suggesting that a cream with a
PC.c is negatively associated with most afterfeel attributes (greasiness, residual film that remains spreadable after 2.5 min is likely to have low
residual coating, and stickiness) suggesting it was perceived to have less friction values. Furthermore, spreadability seems to be negatively
residual coating and to be less greasy and sticky than the other creams. It associated with the yield stress, as a cream with a high yield stress value
was also the cream that is positively associated with tactile friction data. is more likely to be difficult to spread. Negative associations were also
Canoderm®, appears to be positively associated with thickness, and found for moistness and G’, G’’, viscosity, and in vivo hydration data.
negatively associated with moistness. Furthermore, Canoderm® seems Moistness was defined as the amount of liquid or degree of wetness
to be positively associated with rheological data and hydration data and perceived during application. Thus, it is logical to imagine that a thin
differed most from the other three creams in these aspects. SC is influ­ cream with low viscosity is perceived as more moist by the participants.
enced slightly more by application attributes than afterfeel attributes However, skin hydration measurements focus on evaluating water
and is associated with spreadability since it was ranked high for content of the stratum corneum by means of capacitance and conduc­
spreadability and perceived as easy to spread during application. SC is tance, and are not appropriate methods to measure moistness on skin
however negatively associated with friction data, indicating that it has (Berardesca et al., 2018). Thus, we cannot suspect any logical causality
properties that result in low friction values. The PLS suggests that SC.c between moistness and hydration results. The PLS further shows that
had rather weak associations with the various variables, suggesting thickness and softness were positively associated with each other and
‘middle-of-the-road’ physical measures and sensorial responses. associated with viscosity results.
The surfactant-based creams appear to be separated from each other Stickiness could not be related to rheological and tactile friction data.
along the y-axis suggesting slightly different characteristics between the This can be due to that the sensory perception of stickiness is evaluated
creams and mainly associated with hydration and rheological results. by tapping the skin with the fingertip where the movement is different
For instance, differences between a moist and thin cream and a thick and from oscillating movement in rheology and the stroking movement in
fatty cream can be visualized along the y–axis. On the other hand, the tactile friction data. Other studies have found correlation between
relationship between surfactant-based and surfactant-free creams was compression tests and stickiness (Lee et al., 2021; Savary et al., 2019).
mainly explained by the positioning along the x-axis. Furthermore, The present results, as visualized by PLS, suggest that tactile friction
strong differences in afterfeel perception between the surfactant-based experiments could be used to determine sensorial attributes related to
creams due to type of emollient used could to some extent be visual­ afterfeel, and rheological experiments could be used to determine at­
ized by their position along the x–axis. Thus, the differences in tributes relating to the application phase such as thickness, and
composition due to oil:water ratio, type of emollient used, and presence spreadability. These findings appear to be in line with results reported
of thickeners and humectants could mainly be explained by their posi­ by Savary et al. (Savary et al., 2019) and Lee et al. (Lee et al., 2021).
tion along the y–axis, and partly by their position on the x–axis and can
be studied by means of hydration measurements and rheological studies. 4.3. Impact of excipients on sensorial and physical properties

4.2. Relationship between sensory and physical data The results show that the functional excipients used had an impact
on physical properties that could be related to sensorial properties.
Tactile friction results and afterfeel attributes are generally nega­ Humectants were the only exception since the impact of which could
tively associated with each other, while rheological and hydration data only be measured instrumentally, and the moisturizing effect was not
seems to be related to some afterfeel attributes. The PLS further suggests evaluated by perception during the evaluation period. Moreover,
that there seems to be negative associations between absorption and although humectants can give a moisturizing effect that can change the

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A. Ali et al. International Journal of Pharmaceutics 613 (2022) 121370

aesthetics of the skin after long-term use, it is unlikely that this change great possibilities to design surfactant-free creams that can meet the
can be perceived short after one single application. demands for sensitive skin and sustainable skin care products with
The presence of a rheological thickener contributed to the viscosity, unique sensorial properties.
yield stress and the storage stability of creams. Consequently, the vis­ Our results further indicate that to fulfill the requirements of the
cosity and yield stress were mainly related to the initial application and participants in the sensory panel in this particular study, a formulator
spreading of the creams. The two creams with lower viscosity and yield would need to design a cream that is soft upon application, and non-
stress, SC and SC.c, were perceived as easiest to spread. However, SC did greasy in afterfeel, and with a good moisturizing effect. With the
not contain any thickener and differed from SC.c in the emollient knowledge in hand, a combination of the moisturizing property and
composition. Furthermore, SC was also perceived as the moistest and softness of Canoderm® with the non-greasy, non-sticky, powdery
quickest cream to be absorbed during application. Thus, the combina­ afterfeel of PC.c would be needed to fulfill consumer demands.
tion of thickener and emollients is important to consider when designing
a formulation with specific physical properties that can be perceived as 5. Conclusions
cosmetically appealing during the application phase.
Humectants, in combination with occlusive emollients, proved to be The results show that attributes related to the application phase such
very important for sufficient moisturizing effects. Furthermore, the as thickness and spreadability can be predicted by means of rheological
increased skin hydration results after application of Canoderm® high­ measurements, while tactile friction measurements on excised skin can
lights the difference in hydration efficiency between urea and glycerol be used to predict certain sensorial attributes related to the afterfeel
(present in SC.c). The perception study did not emphasize any effect in sensation.
sensorial properties that could be related to the moisturizing effect. The type of emollients used, surfactant composition, as well as the
However, small differences regarding tactile friction between Can­ presence of thickeners had the greatest impact on the difference in
oderm® and SC, could perhaps be related to increased skin hydration for rheological and sensory properties among surfactant-based creams.
skin samples treated with Canoderm®. This observation is in agreement Differences between a starch-based Pickering cream and surfactant-
with similar observations made by Lodèn (Lodén et al., 1992) and based creams were more evident in relation to the afterfeel attributes,
Skedung (Skedung et al., 2016), however in neither case was skin hy­ and easily distinguished using tactile friction measurements.
dration measured. A starch-based, surfactant-free Pickering cream with higher friction
The choice of the right emollient composition is important for the coefficient values ranked low for greasiness, stickiness, slipperiness, and
sensorial properties of a cream. The results showed that the different softness.
emollient composition may be the explanation for the difference seen
between the surfactant-based creams. Canoderm® and SC.c were ranked
CRediT authorship contribution statement
highest for softness. However, due to the variety of emollients used in
the emollient mixture it was not possible to conclude which type of
A Ali: Conceptualization, Methodology, Validation, Formal analysis,
emollient that had a greater influence on the physical and sensorial
Investigation, Writing – original draft, Writing – review & editing,
properties. The amount of emollient used in the prototype creams (PC.c,
Visualization, Project administration. L Skedung: Conceptualization,
SC, SC.c) was almost similar (28–30 wt%) while Canoderm® can be
Methodology, Writing – review & editing, Formal analysis. S Burleigh:
assumed to have lower emollient concentration with different surfactant
Formal analysis, Writing – review & editing. E Lavant: Investigation,
composition (patent SE511551.C2).
Writing – review & editing. L Ringstad: Conceptualization, Methodol­
The use of starch particles replacing traditional surfactants as
ogy, Writing – review & editing. CD Anderson: Conceptualization,
emulsion stabilizers in a cream resulted in large differences in the
Methodology, Writing – review & editing. M Wahlgren: Conceptuali­
perceived sensory properties, as well in the physical properties of the
zation, Methodology, Supervision, Writing – review & editing. J Eng­
cream. These differences resulted in lower rank preference for sensory
blom: Conceptualization, Methodology, Supervision, Project
attributes important during the application phase of creams. Nonethe­
administration, Writing – review & editing, Funding acquisition.
less, the overall sensorial benefit of the addition and use of starch par­
ticles as emulsion stabilizers could be related to the afterfeel sensation of
creams. Generally unpleasant afterfeel attributes such as perception of a Declaration of Competing Interest
residual coating, stickiness and greasiness can be reduced and replaced
by the sensation of a dry, powdery afterfeel. Similar results have been The authors declare that they have no known competing financial
reported for inorganic particles in the residual oil film (Terescenco et al., interests or personal relationships that could have appeared to influence
2020),where the particles affected the properties of the residual film. the work reported in this paper.
Interestingly, PC.c was not perceived as a thick cream during the
application, although the rheological results showed higher viscosity Acknowledgements
and yield stress values than for SC.c. Furthermore, PC.c was not
considered soft and smooth, and one explanation could be that the as­ We are grateful to the Knowledge foundation (Sweden) for funding
sessor’s connected soft and smooth to the thickness and body of the the project, and Johan Engblom also thank the Gustaf Th Ohlsson
cream, rather than the soft afterfeel sensation as a result of presence of foundation (Sweden) for financial support. Speximo AB is acknowledged
particles. Instead, Canoderm® and SC.c were considered thick and soft, for providing starch particles.
and this could be connected to presence of fatty alcohols among the
surfactants, contributing to the body and thickness of the creams that Appendix A. Supplementary material
can be perceived as soft, cushioning, and smooth.
Despite the low number of formulations tested in this study, the re­ Supplementary data to this article can be found online at https://doi.
sults clearly demonstrate the impact of replacing surfactants with sta­ org/10.1016/j.ijpharm.2021.121370.
bilizing particles on the sensory and physical properties of a cream. We
can conclude that the right combination of a thickener, humectant, References
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