Enhanced efficacy and sensory properties of an anti-dandruff shampoo containing zinc pyrithione and climbazole

Abstract

Synopsis
Dandruff is a common complaint and is suffered by as much as half of the population at some time post puberty. The condition is characterized by the presence of flakes on the scalp and in the hair, and is often accompanied by itch. The most common treatment for dandruff is the use of shampoo formulations that contain fungistatic agents such as zinc pyrithione (ZPT) and octopirox. Whilst most antidandruff shampoos are effective in resolving the symptoms of dandruff these shampoos can often result in hair condition that is less than acceptable to consumers which can lead to a tendency for them to revert to use of a non‐antidandruff shampoo. This can result in a rapid return of dandruff symptoms.
The aim of this investigation was to study the impact of using a combination of antidandruff actives and silicones on the resolution of dandruff and to deliver superior sensory properties to the hair. We have demonstrated that shampoo containing the dual active system of ZPT/Climbazole deposits both active agents onto a model skin surface (VitroSkin) and reduces Malassezia furfur regrowth in vitro. Clinical evaluation of the dual active shampoo demonstrated superior efficacy and retained superiority during a regression phase where all subjects reverted to using a non‐antidandruff shampoo. We have also demonstrated that it is possible to deposit silicone materials from antidandruff shampoo uniformly over both virgin and damaged hair fibres that results in smoother hair fibres (as evidenced by reduced dry friction). This combination of antidandruff agents and conditioning silicones delivered from a shampoo provides subjects with superior antidandruff efficacy and desired end sensory benefits ensuring compliance and longer term dandruff removal.

Full text

Enhanced efficacy and sensory properties of an anti-dandruff
shampoo containing zinc pyrithione and climbazole
G. A. Turner*, J. R. Matheson*, G.-Z. Li
†
, X.-Q. Fei
†
, D. Zhu
†
and F. L. Baines*
*Unilever Research & Development Port Sunlight, Quarry Road East, Bebington Merseyside, CH63 3JW, U.K. and
†
Unilever Research & Development
Centre Shanghai, 66 Linxin Road, Linkong Economic Development Zone, Changning District Shanghai, 200335, China
Received 23 July 2012, Accepted 07 September 2012
Keywords: breakage, dandruff, hair, Malassezia, scalp
Synopsis
Dandruff is a common complaint and is suffered by as much as half
of the population at some time post puberty. The condition is char-
acterized by the presence of flakes on the scalp and in the hair,
and is often accompanied by itch. The most common treatment for
dandruff is the use of shampoo formulations that contain fungi-
static agents such as zinc pyrithione (ZPT) and octopirox. Whilst
most antidandruff shampoos are effective in resolving the symp-
toms of dandruff these shampoos can often result in hair condition
that is less than acceptable to consumers which can lead to a ten-
dency for them to revert to use of a non-antidandruff shampoo.
This can result in a rapid return of dandruff symptoms.
The aim of this investigation was to study the impact of using a
combination of antidandruff actives and silicones on the resolution
of dandruff and to deliver superior sensory properties to the hair.
We have demonstrated that shampoo containing the dual active
system of ZPT/Climbazole deposits both active agents onto a model
skin surface (VitroSkin) and reduces Malassezia furfur regrowth in
vitro. Clinical evaluation of the dual active shampoo demonstrated
superior efficacy and retained superiority during a regression phase
where all subjects reverted to using a non-antidandruff shampoo.
We have also demonstrated that it is possible to deposit silicone
materials from antidandruff shampoo uniformly over both virgin
and damaged hair fibres that results in smoother hair fibres (as evi-
denced by reduced dry friction). This combination of antidandruff
agents and conditioning silicones delivered from a shampoo pro-
vides subjects with superior antidandruff efficacy and desired end
sensory benefits ensuring compliance and longer term dandruff
removal.
Re
´sume
´
Les pellicules constituent un proble
`me fre
´quent et concernent a
`peu
pre
`s la moitie
´de la population a
`un moment post pubertaire. La
condition est caracte
´rise
´e par la pre
´sence de paillettes sur le cuir
chevelu et les cheveux, et elle est souvent accompagne
´ede
de
´mangeaisons. Le traitement le plus courant pour les pellicules est
l’utilisation de formulations de shampooing qui contiennent des
agents fongistatiques comme le zinc pyrithione (ZPT) et octopirox.
Alors que la plupart des shampooings antipelliculaires soient effic-
aces dans la re
´solution des sympto
ˆmes des pellicules, ces shampoo-
ings peuvent souvent entraıˆner des e
´tats des cheveux non
acceptables pour les consommateurs qui peuvent conduire a
`une
tendance a
`revenir a
`l’utilisation d’un shampooing non-antipellicu-
laire. Cela peut entraıˆner un retour rapide des sympto
ˆmes de pelli-
cules. Le but de cette e
´tude e
´tait d’e
´tudier l’impact de l’utilisation
d’une combinaison de principes actifs antipelliculaires et silicones
sur la re
´solution de pellicules et de fournir de meilleures proprie
´te
´s
sensorielles pour les cheveux. Nous avons de
´montre
´qu’un sham-
pooing contenant le syste
`me dual active de ZPT/Climbazole de
´pose
les deux agents actifs sur une surface de la peau du mode
`le (Vitro-
Skin) et re
´duit la repousse de Malassezia furfur in vitro. L’e
´valuation
clinique du shampooing double actif a montre
´une efficacite
´supe
´ri-
eure et a conserve
´une supe
´riorite
´lors d’une phase de re
´gression
ou
`tous les sujets e
´taient revenus a
`un shampoing non-antipellicu-
laire. Nous avons e
´galement de
´montre
´qu’il est possible de de
´poser
des mate
´riaux en silicone d’un shampooing antipelliculaire unifor-
me
´ment sur les fibres capillaires vierges et/ou endommage
´es, ce qui
se traduit par des fibres de cheveux lisses (comme on en te
´moigne
par une re
´duction du frottement a
`sec). Cette combinaison d’agents
antipelliculaires et silicones de conditionnement fournis a
`partir
d’un shampooing apporte aux utilisateurs une efficacite
´antipellicu-
laire supe
´rieure et les avantages sensoriels finaux souhaite
´s, assu-
rant l’utilisation durable et a
`long terme l’e
´limination des
pellicules.
Introduction
Dandruff is a common complaint and is suffered by as much as half
of the population at some time post puberty [1]. The condition is
generally characterized by the presence of flakes on the scalp and
in the hair, and is often accompanied by itch. The severity of dan-
druff in the population can range from mild scale formation (simi-
lar to that of dry skin) to seborrhoeic dermatitis (SD) [2–4]. The
central hypothesis of the aetiology of dandruff states that the lipo-
philic yeast, Malassezia, is the causal agent. The debate about the
role of Malassezia in the formation of dandruff, and SD, has contin-
ued since the first report of the association of this species with dan-
druff in 1874 [5]. The evidence implicating Malassezia species in
formation of dandruff has been generated over a number of years.
Essentially, this comes from observations that the levels of
Correspondence: Graham A. Turner, Unilever Research & Development
Port Sunlight, Quarry Road East, Bebington, Merseyside CH63 3JW,
U.K. Tel.: +44 151 641 3705; fax: +44 151 641 1843; e-mail: graham.
turner@unilever.com
Presented at the World Congress of Dermatology, Seoul 2011 and the IFSCC Conference,
Bangkok, 2011
©2012 Society of Cosmetic Scientists and the Socie
´te
´Franc¸aise de Cosme
´tologie78
International Journal of Cosmetic Science,2013,35, 78–83 doi: 10.1111/ics.12007

Malassezia (especially, M. globosa and M. restricta) species are ele-
vated in dandruff, whereas the levels of other micro-organisms
remain constant. For example, McGinley et al. found that Mala-
ssezia made up 46% of the microbial flora in normal subjects, 74%
of the flora in patients with dandruff and 83% of the flora in cases
of SD [6,7]. Further support for the association of Malassezia with
the dandruff condition comes from the observation that the most
effective anti-dandruff treatments are anti-fungal agents [e.g. zinc
pyrithione (ZPT), piroctone olamine, selenium sulphide and ketoco-
nazole] and that improvement of the dandruff condition with such
ingredients is correlated with removal of the yeast [8–12].
Malassezia is a commensal organism that is found on healthy
scalps as well as on dandruff scalps [13]. Initially, no pathogenic
mechanism could be associated with the deterioration from a healthy
to a dandruff scalp [14]. Subsequent work has recognized a role for
lipid metabolism via lipase action from Malassezia species. More spe-
cifically, the role of oleic acid [15] as an initiator of dandruff has been
proposed [13]. These observations imply that other factors must play
a role in the development of dandruff on susceptible individuals. Mal-
assezia spp. have also been found to trigger an innate immune
response, possibly mediated by an upregulation of toll-like receptors
(TLRs), especially TLR-2. It is possible that Malassezia may induce
inflammation in the scalp to trigger dandruff symptoms by this
mechanism [16,17]. It is true to say that dandruff has a multifacto-
rial aetiology that includes Malassezia colonization, some underlying
propensity to hyperproliferation, altered corneocyte maturation pro-
cesses and a sub-clinical microinflammatory state. Furthermore, it
has been shown that clear changes to the stratum corneum lipid
composition are present in dandruff, in both their amount and
relative composition and that there are significant changes to a
range of biomarkers of inflammation, including IL-1a[18,19].
The dandruff state is also reflected in changes in the biophysical
properties of the skin (which may be directly related to the changes in
stratum corneum lipid content and ratio). For example, the transepi-
dermal water loss of dandruff scalp is higher than that of healthy scalp
[20]. This is indicative of a perturbed stratum corneum barrier. An
investigation into the alteration of scalp stratum corneum intercellular
lipid levels in response to a ZPT anti-dandruff shampoo has demon-
strated restoration in scalp intercellular lipids [21]. ZPT treatment sig-
nificantly increased levels of triglycerides, cholesterol and ceramides.
These findings complemented those of a recent study in which ZPT
was demonstrated to improve the scalp ultrastructure, normalizing
the parakeratotic nature of dandruff skin [22]. It has been stated previ-
ously that Malassezia species are associated with dandruff formation.
However, the observation that Malassezia are commensal organisms
and that most people have Malassezia on scalp but not all people have
dandruff, implies that other changes in the underlying scalp biology
may be contributing to the development of dandruff [23].
The most common treatment for dandruff is the use of shampoo
formulations that most often contain fungistatic agents. Whilst
most anti-dandruff shampoos are effective in resolving the symp-
toms of dandruff, these shampoos can often result in hair condition
that is less than acceptable to consumers [24] which, in turn, can
lead to a tendency for them to revert to a non-anti-dandruff sham-
poo. This can have the effect of a rapid return of dandruff symp-
toms. To increase compliance, anti-dandruff shampoos must be
formulated to deliver the anti-dandruff agent effectively to the scalp
whilst providing excellent hair fibre properties.
The aim of the current investigation was to study the impact of
using a combination of anti-dandruff actives on the resolution of
dandruff and to deliver superior sensory properties to the hair. The
anti-dandruff actives selected for this study comprised a combina-
tion of zinc pyrithione (1% w/w) and the anti-fungal agent, climb-
azole (0.5% w/w). Climbazole is an imidazole anti-fungal agent
that has been demonstrated to be delivered effectively from anti-
dandruff shampoos and to inhibit Malassezia growth [25,26]. The
test formulations were further enhanced using a unique combina-
tion of silicones to maximize sensory properties. The anti-dandruff
efficacy of this novel dual active system was compared with a com-
mercial 1% zinc pyrithione-containing shampoo.
Materials and methods
Test shampoo formulations
Three shampoo formulations were tested.
•ZPT/climbazole shampoo: 1% (w/w) ZPT, 0.5% (w/w) climbaz-
ole, two silicone emulsions [Silicone 1: Dimethiconol (and) TEA-
dodecylbenzenesulfonate; Silicone 2: Dimethicone (and) C12-15
Pareth-3 (and) C12-15 Pareth-23 (and) Poloxamer 407]
•ZPT shampoo: commercially available shampoo containing 1%
(w/w) ZPT, dimethicone
•Standard beauty shampoo: commercially available shampoo
without anti-dandruff actives
Generation of damaged hair switches
Damaged hair switches were prepared by bleaching and dyeing
dark brown European hair switches. Bleaching solution was
prepared according to the manufacturers instructions (L’Ore
´al Pla-
tine Precision) and applied to each side of the switches using a col-
ouring brush. The switches were wrapped in aluminium foil and
left for 30 min. The switches were then rinsed under tap water and
left to dry for 1 h at 50°C. The switches were then washed in SLES
solution and dried overnight at ambient conditions. The bleached
switches were then dyed using Wella Koleston Perfect 710.
In vitro studies
Determination of silicone deposition to hair fibres
Silicone deposition from shampoo formulations was measured using
X-ray fluorescence spectroscopy (XRF) with an Axios PW 1596
spectrometer with Super Q software. Dark brown, straight European
hair switches, 3 g, (n=5) were soaked in diethyl ether for 30 min
and then swirled in 20% (w/w) hot sodium lauryl ether sulphate
1EO (SLES 1EO) to remove the ether. Diethyl ether was used as a
safe and effective method to remove residual silicone on hair
switches. The switches were then washed in SLES 1EO two further
times and allowed to dry in a fume hood for approx. 20 min. Hair
switches were placed in Petri dishes and had 540 lL water and
60 lL of test shampoo applied along the length of the switch. The
switch was then massaged for 1 min and the lather left in situ for
1 min to simulate the washing process. The treated switches were
then rinsed for 30 s with tap water (3 L min
1
). The switches were
allowed to dry in ambient conditions overnight. Five replicates were
prepared for each sample to be tested. Hair switches were divided
into thirds to represent tip, middle and root prior to XRF analysis.
Treated hair switch segments were placed in the XRF cups in a par-
allel manner and secured in the cup. Output from the XRF spec-
trometer (count rate) was converted to concentration of silicon
with reference to a standard curve. Data were analysed using one
©2012 Society of Cosmetic Scientists and the Socie
´te
´Franc¸aise de Cosme
´tologie
International Journal of Cosmetic Science,35, 78–83 79
Antidandruff shampoo containing ZPT and climbazole G. A. Turner et al.

way ANOVA, a result was considered to be statistically significant if
the P-value for the F-test was <0.05.
Determination of zinc deposition to VitroSkin
TM
The sheet VitroSkin
TM
was divided into 5 95 cm pieces and
placed over one side of the smaller diameter XRF ring, with the
rough topography facing downwards. The larger ring was then
placed onto the smaller ring and pressed firmly to ensure a good
seal, ensuring that the rough topography of the artificial skin was
inside the cups. Distilled water (1.5 mL) and shampoo (0.5 mL)
were pipetted into the XRF plastic cup and mixed onto the surface
of the artificial skin using the stirring rod for 30 s (the surface of
the stirring rod remaining in contact with the surface of the artifi-
cial skin). The shampoo solution was then removed using a plastic
pipette and a rinse phase simulated using 2 mL of distilled water
and a 30 s application time. Finally, all rinse water was removed
using a pipette, and the XRF cups were allowed to dry overnight in
ambient conditions. Output from the XRF spectrometer (count rate)
was converted to concentration of zinc with reference to a standard
curve. Data were analysed using one way ANOVA, a result was
considered to be statistically significant if the P-value for the F-test
was <0.05.
Determination of fungistatic activity
Fungistatic activity of the shampoo formulations was assessed by
inoculation of Malassezia furfur onto VitroSkin that had been trea-
ted with shampoo in XRF cups in a manner similar to that
described for assessment of zinc deposition. This is an attempt to
gauge fungistatic activity on a surface following a wash and rinse
procedure simulating a typical shampoo treatment. Malassezia fur-
fur is commonly used as a model fungal species rather than using
M.restricta or M.globosa as it is relatively easy to grow in culture
on a VitroSkin surface. After allowing the treated XRF cells to dry
overnight, the samples were placed into jars containing Modified
Dixon agar. 200 lL of a suspension of M. furfur CB 1878
(2–6910
6
cells mL
1
) was inoculated onto the surface of the
substrate and incubated for 24 h at 32°C. After this period of
incubation, the cells were harvested with buffer solution and
100 lL of a 10-fold dilution spread onto replicate Modified Dixon
Agar plates and incubated for 3–4 days at 32°C. Data were
analysed using one way ANOVA; a result was considered to be sta-
tistically significant if the P-value for the F-test was <0.05.
Assessment of hair smoothness
Hair smoothness was measured using a Texture Analyser (TA.XT.
Plus Stable Microsystems. Godalming, Surrey, U.K.). Hair switches
(3 g; 16 cm 94 cm) were secured in an aluminium frame and
cleaned under tap water (37°C) at a flow rate of 4 L min
1
, for
5 s. 14% (w/w) sodium lauryl ether sulphate (2EO) (1.25 g) was
applied to each of the switches and agitated for 30 s and then
rinsed for 30 s under tap water. This wash cycle was repeated and
each switch combed through to align the fibres. Following this pre-
treatment, the switches were treated with the treatment shampoo
formulations using the same application protocol and tested after
overnight drying (22°C, 50% RH). Smoothness of the hair switches
was measured on the Texture Analyser by moving a probe for a
total distance of 80 mm (2 940 mm) at 10 mm s
1
and 500 g
load. The area of each friction hysteresis loop was calculated and
reported as g.mm. Five switches were measured for each wash
treatment. Data were analysed using Student’s t-test. Results were
considered to be significant at the 95% confidence level.
In vivo studies
Anti-dandruff efficacy study design
The study was carried out in Bangkok, Thailand at the Unilever
internal facility and was a double-blind, randomized, half-head
design. The study was cleared by the Joint Research Ethics Com-
mittees, Bangkok, and all subjects gave their informed consent to
participate. Men with dandruff were recruited and put onto a
4 week run-in phase where they used a beauty shampoo at home.
Those men who still had dandruff at the end of the run-in phase
continued onto the test phase of the study (n=69). Subjects had
their hair washed three times per week in a salon using a half-
head procedure where half the head was washed with ZPT/climb-
azole shampoo and the other half was washed with ZPT-only
shampoo. The side of head treated with each product was ran-
domly allocated. Treatment continued for 4 weeks after which time
subjects returned to use of a beauty shampoo at home for a further
2 weeks (regression phase). Sixty subjects completed the test phase
of the study and 58 completed the regression phase. Dandruff was
measured using the Unilever Total Weighted Head Score (TWHS)
system [18] at baseline and at weekly intervals over the study.
TWHS was assessed 48 hours after the final application of sham-
poo. The mean TWHS adhered flake (AF) score for each subject/
treatment was used as a summary measure of treatment perfor-
mance during the test phase and during the regression phase. The
mean TWHS AF was only calculated for subjects with complete
data. Analysis of covariance was used to analyse the mean test
phase data and the mean regression phase data. Baseline measure-
ment was treated as a covariate, treatment as a fixed effect and
subject as a random effect. Results were considered to be significant
if the F-test P-value was <0.05.
Results and discussion
Anti-dandruff active deposition
Table I shows the results of the deposition studies from zinc pyrithi-
one/climbazole shampoo and zinc pyrithione shampoo. Both actives
were readily detected on the VitroSkin
TM
after the simulated wash
protocol. The zinc pyrithione/climbazole shampoo deposited signifi-
cantly more zinc than the ZPT shampoo (P<0.05).
In vitro inhibition of Malassezia
Inhibition of the growth of Malassezia furfur by the two zinc pyrithi-
one-containing shampoos is presented in Fig. 1. The data are pre-
sented as log Malassezia number reduction. It can be seen that the
zinc pyrithione/climbazole formulation was significantly more effec-
Table I Zinc and climbazole deposition to VitroSkin
TM
Zinc (lgcm
2
)
Mean ±SD
Climbazole (lgcm
2
)
Mean ±SD
ZPT/Climbazole 14.83 ±1.81 3.17 ±0.41
ZPT 11.10 ±1.59 ND
ND, not detected; ZPT, zinc pyrithione.
©2012 Society of Cosmetic Scientists and the Socie
´te
´Franc¸aise de Cosme
´tologie
International Journal of Cosmetic Science,35, 78–8380
Antidandruff shampoo containing ZPT and climbazole G. A. Turner et al.

tive at inhibiting growth of Malassezia furfur than the ZPT shampoo
(P<0.05).
Anti-dandruff efficacy
The results of the anti-dandruff study are presented in Fig. 2. Zinc
pyrithione/climbazole shampoo was significantly more effective
than the ZPT shampoo at reducing the clinically observed dandruff
flakes over the 4 week test phase (95% CI 3.3 to 0.8,
P<0.002). During the regression phase, the zinc pyrithione/climb-
azole shampoo retained its anti-dandruff superiority over the ZPT
shampoo (95% CI 7.4 to 4.1, P<0.001).
Silicone deposition
Silicone deposition onto virgin and damaged hair is presented in
Table II. The ZPT/climbazole shampoo, containing two silicone
ingredients [Silicone 1: Dimethiconol (and) TEA-dodecylbenzene-
sulfonate; silicone 2: Dimethicone (and) C12-15 Pareth-3 (and)
C12-15 Pareth-23 (and) Poloxamer 407] was found to deposit sig-
nificant levels of silicone onto the whole of the hair fibre (root, mid-
dle and tip) when compared to a Standard shampoo (free from
anti-dandruff actives but containing silicone) on both virgin hair
and damaged hair. The level of deposition of silicone was signifi-
cantly higher from the ZPT/climbazole shampoo than from the
Standard shampoo (P<0.05). No silicone deposition was detected
from the Standard shampoo onto damaged hair, whereas silicone
deposition was observed along all parts of the hair fibre from the
ZPT/climbazole shampoo. The level of silicone deposition onto dam-
aged hair was much lower than that measured on virgin hair.
Hair smoothness
Hair smoothness was assessed using a measure of the dry friction
force following treatment with shampoo. The results are presented
in Fig. 3. The ZPT/climbazole shampoo was found to generate sig-
nificantly lower dry frictional force than the Standard shampoo
(P<0.05) on both virgin and damaged hair.
Conclusions
Dandruff is a common cosmetic complaint that afflicts many people
at some point in their life. There are many shampoos available, in
both supermarkets and pharmacies, to combat dandruff using cos-
metic ingredients (for the majority of the world) or active ingredients
Figure 1 Malassezia inhibition on VitroSkin (mean ±SD, P<0.05) zinc
pyrithione (ZPT)/climbazole shampoo showed a significant inhibition of
growth of Malassezia furfur in this test and in repeat studies, P<0.05, when
compared to the ZPT shampoo.
30
40
50
ZPT/Climbazole
ZPT
0
10
20
0123456
Week
TWHS AF (Means ± 95% CI)
Active phase Regression phase
Figure 2 Antidandruff efficacy through active and regression phase. Dual
active formulation (ZPT/climbazole) showed superior antidandruff efficacy
compared to ZPT-only shampoo over the 4 week test period and over the
2 week regression phase.
Table II Silicone deposition to virgin and damaged hair as determined by X-ray fluorescence
Silicone deposition, lgg
1
(mean ±SD)
Virgin hair Damaged hair
Root Middle Tip Root Middle Tip
ZPT/Climbazole 2888 ±463 1755 ±310 1766 ±65 437 ±109 428 ±52 337 ±23
Standard shampoo (No AD active) 2025 ±688 1481 ±317 852 ±464 ND ND ND
ND, not detected.
©2012 Society of Cosmetic Scientists and the Socie
´te
´Franc¸aise de Cosme
´tologie
International Journal of Cosmetic Science,35, 78–83 81
Antidandruff shampoo containing ZPT and climbazole G. A. Turner et al.

supported by the FDA Monograph in the United States (where anti-
dandruff shampoos are considered to be drugs). The most common
ingredient for treatment of the dandruff condition is ZPT. This fun-
gistatic agent controls dandruff by limiting the regrowth of Mala-
ssezia species that have been strongly implicated in the aetiology of
the condition. Despite its proven efficacy, the sensory properties of
ZPT-based anti-dandruff shampoos leave much to be desired. The
primary aim of many cosmetic shampoos is to clean the hair and
allow the subject to generate their preferred hair style with the rel-
evant sensory cues (such as conditioned benefit, control of fibre
damage, fragrance.) [24]. In the case of ZPT-based anti-dandruff
shampoos, there is a subject-perceived deficiency in the cosmetic/
sensory performance. This perceived deficiency leads to subjects
switching from an anti-dandruff shampoo to a standard shampoo
in the belief that they will achieve superior cosmetic end benefits.
Consequently, the dandruff condition will recur within a short per-
iod of time. The present investigations have been carried out to
identify a formulation that provides both enhanced anti-dandruff
efficacy and no loss in sensory and cosmetic properties on the hair.
Such a formulation will prove invaluable in the prolonged control
of dandruff as subject compliance with product use instructions will
be enhanced.
A pre-requisite of any anti-dandruff formulation is to ensure that
the active ingredient is: (i) deposited onto the scalp surface from a
shampoo; (ii) reduces growth of the Malassezia species.
In the present research, we have demonstrated that the dual
active system of ZPT/climbazole deposits both active agents onto a
model skin surface (VitroSkin). Furthermore, the deposited ingredi-
ents also reduce Malassezia furfur regrowth. Taken together the
deposition data and Malassezia inhibition data allow us to screen a
formulation before moving onto an in vivo clinical study on human
subjects. Clinical evaluation of the dual active system in the present
study demonstrated that this novel anti-dandruff combination
(ZPT/climbazole) is significantly better that ZPT-alone in reducing
dandruff on the human scalp when delivered from shampoo formu-
lations. The dual active system not only reduces dandruff flakes in
the test phase but retains the superiority during a regression phase
when subjects revert to using a non-anti-dandruff shampoo.
The sensory and fibre care properties of anti-dandruff shampoos
are essential to ensure that subjects comply with usage instructions
and continue to use the product to remove dandruff. By careful
selection of conditioning ingredients (e.g. silicones), it is possible to
achieve the aim of anti-dandruff efficacy and hair sensory benefits.
We have been able to demonstrate that by selecting the correct
combination of silicones, it is possible to coat uniformly over both
virgin and damaged hair fibres. This is not achieved by the com-
monly used silicones in “beauty” shampoos (i.e. non-anti-dandruff
shampoos) as exemplified by the Standard shampoo in the present
investigation. This in turn results in smoother hair fibres (as evi-
denced by reduced dry friction), which drives consumer compli-
ance. This combination of anti-dandruff agents and conditioning
silicones provides subjects with anti-dandruff efficacy and desired
end hair sensory benefits ensuring compliance and longer term
remission from dandruff.
Acknowledgements
The authors wish to thank Nittaya Srisuwankul and team for
running the anti-dandruff study. This work was totally funded by
Unilever Plc.
References
1. Saint Le
´ger, D.. Dandruff (pityriasis captis
simplex): of yeasts and men. In: The Science
of Hair Care, 2nd edn (Bouillon, C. and Wil-
kinson, J., eds), pp. 609–631. Tailor and
Francis, Boca Raton, New York (2005).
2. Hay, R.J. and Graham-Brown, R.A.C. Dan-
druff and seborrhoeic dermatitis: causes and
management. Clin. Exp. Dermatol. 22,3–6
(1997).
3. Hay, R.J. Malassezia, dandruff and
seborrhoeic dermatitis: an overview. Br. J.
Dermatol. 165,2–8 (2011).
4. Pie
´rard-Franchimont, C. and Pie
´rard, G.E.
Certitudes, controversies et confusions
se
´mantiques autour des pellicules. Skin 1,
16–19 (1998).
5. Malassez, R. Note sur les champignon du
pityriasis simplex. Arch. Physiol. 1, 451
(1874).
6. McGinley, K.J., Leyden, J.J., Marples, R.R.
and Kligman, A.M. Quantitative microbiol-
ogy of the scalp in non-dandruff, dandruff
and seborrhoeic dermatitis. J. Invest. Derma-
tol. 64, 401–405 (1975).
7. Pie
´rard-Franchimont, C., Arrese, J.E.,
Durupt, G., Ries, G., Cauwenbergh, G. and
Pie
´rard, G.E. Correlation between Malassezia
spp.load and dandruff severity. J. Mycol.
Me
´d. 8,83–86 (1998).
8. Kligman, A.M., Marples, R.R., Lantis, L.R.
and McGinley, K.J. Appraisal of efficacy of
antidandruff formulations. J. Soc. Cosmet.
Chem. 25,73–91 (1974).
9. Pie
´rard, G.E., Arrese, J.E., Pie
´rard-Franchi-
mont, C. and De Doncker, R.P. Prolonged effect
of antidandruff shampoos –time to recurrence
of Malassezia ovalis colonization of the skin. Int.
J. Cosmet. Sci. 19,111
–117 (1997).
10. Marks, R., Pearse, A.D. and Walker, A.P.
The effects of a shampoo containing zinc
pyrithione on the control of dandruff. Br. J.
Dermatol. 112, 415–422 (1985).
11. Shuster, S. The aetiology of dandruff and
the mode of action of therapeutic agents.
Br. J. Dermatol. 111, 235–242 (1984).
*
40 000
60 000
Virgin hair
Damaged hair
0
20 000
ZPT/Climbazole ZPT
Dry friction force (g.mm)
Figure 3 Dry friction force on switches treated with antidandruff shampoos
(mean ±SEM, *P<0.05) Dry friction force for the ZPT/climbazole shampoo
was lower than that found with the shampoo containing ZPT alone. This
result was significantly significant on damaged hair but not on virgin hair.
©2012 Society of Cosmetic Scientists and the Socie
´te
´Franc¸aise de Cosme
´tologie
International Journal of Cosmetic Science,35, 78–8382
Antidandruff shampoo containing ZPT and climbazole G. A. Turner et al.

12. Reeder, N.L., Xu, J., Youngquist, R.S.,
Schwartz, J.R., Rust, R.C. and Saunders, C.
W. The antifungal mechanism of action of
zinc pyrithione. Br. J. Dermatol. 165,9–12
(2011).
13. Dawson, T.L. Malassezia globosa and restricta:
breakthrough understanding of the etiology
and treatment of dandruff and seborrhoeic
dermatitis through whole-genome analysis.
J. Investig. Dermatol. Symp. Proc. 12,15–19
(2007).
14. Faergemann, J. Pityrosporum species as a
cause of allergy and infection. Allergy 54,
413–419 (1999).
15. DeAngelis, Y.M., Gemmer, C.M., Kaczvinsky,
J.R., Keneally, D.C., Schwartz, J.R. and
Dawson, T.L. Three etiologic facets of dan-
druff and seborrheic dermatitis: Malassezia
fungi, sebaceous lipids, and individual sensi-
tivity. J. Investig. Dermatol. Symp. Proc. 10,
295–297 (2005).
16. Ashbee, H.R. Update on the genus Mala-
ssezia.Med. Mycol. 45, 287–303 (2007).
17. Baroni, A., Orlando, M., Donnarumma, G.,
Farro, P., Iovene, M.R., Tufano, M.A. and
Buommino, E. Toll-like receptor 2 (TLR2)
mediates intracellular signaling in human
keratinocytes in response to Malassezia furfur.
Arch. Dermatol. Res. 297, 280–288 (2006).
18. Harding, C.R., Moore, A.E., Rogers, J.S.,
Meldrum, H., Scott, A.E. and McGlone, F.P.
Dandruff: a condition characterized by
decreased levels of intercellular lipids in
scalp stratum corneum and impaired barrier
function. Arch. Dermatol. Res. 294, 221–
230 (2002).
19. Kerr, K., Darcy, T., Henry, J. et al. Epidermal
changes associated with symptomatic reso-
lution of dandruff: biomarkers of scalp
health. Int. J. Dermatol. 50, 102–113
(2011).
20. Billhimer, W., Erb, J. and Bacon, R. Sham-
pooing with pyrithione zinc shampoo
reduces transepidermal water loss in scalp of
dandruff-involved patients. J. Am. Acad. Der-
matol. 54, AB131 (2006).
21. Rogers, J.S., Moore, A.E., Meldrum, H. and
Harding, C.R. Increased scalp lipids in
response to antidandruff treatment contain-
ing zinc pyrithione. Arch. Dermatol. Res.
295, 127–129 (2003).
22. Warner, R.R., Schwartz, J.R., Boissy, Y. and
Dawson, T.L. Dandruff has altered stratum
corneum ultrastructure that is improved
with zinc pyrithione shampoo. J. Am. Acad.
Dermatol. 45, 897–903 (2001).
23. Turner, G.A., Hoptroff, M. and Harding, C.R.
Stratum corneum barrier dysfunction in
dandruff. Int. J. Cosmet. Sci. 34, 285–387
(2012).
24. Draelos, Z.D., Kenneally, D.C., Hodges, L.T.,
Billhimer, W., Copas, M. and Margraf, C. A
comparison of hair quality and cosmetic
acceptance following the use of two anti-
dandruff shampoos. J. Investig. Dermatol.
Symp. Proc. 10, 201–204 (2005).
25. Mayser, P., Argembaux, H. and Rippke, F.
The hair strand test –a new method for
testing antifungal effects of antidandruff
preparations. J. Cosmet. Sci. 54, 263–270
(2003).
26. Schmidt-Rose, T., Braren, S., Fo¨ lster, H.
et al. Efficacy of a piroctone aolamine/climb-
azole shampoo in comparison with a zinc
pyrithione shampoo in subjects with moder-
ate to severe dandruff. Int. J. Cosmet. Sci.
33, 276–282 (2001).
©2012 Society of Cosmetic Scientists and the Socie
´te
´Franc¸aise de Cosme
´tologie
International Journal of Cosmetic Science,35, 78–83 83
Antidandruff shampoo containing ZPT and climbazole G. A. Turner et al.