cosmetics

Article
The New Sunscreens among Formulation Strategy,
Stability Issues, Changing Norms, Safety and
Efficacy Evaluations
Nicola Lionetti 1 and Luigi Rigano 2, *
1 Rigano Laboratories S.r.l., 20125 Milano, Italy; [email protected]
2 ISPE, Institute of Skin and Product Evaluation, 20125 Milano, Italy
* Correspondence: [email protected]

Academic Editors: Marisanna Centini and Cecilia Anselmi

Received: 27 March 2017; Accepted: 9 May 2017; Published: 16 May 2017

Abstract: The sun-and-skin interactions have controversial sides. Besides important beneficial
effects, we need to take into consideration also some serious harmful results. In particular, these
are connected to the portion of the solar spectrum traditionally identified as ultraviolet type A and
B. The topical application of sunscreens (and the avoidance of extreme exposure to sun rays) is
worldwide recognized as the best strategy to avoid sunburn and oedema. Moreover, such strategy
can efficiently prevent the onset of skin cancer. Therefore, the first aim of sunscreen products is
to efficiently minimize all damage of sun exposure, while, at the same time, keeping good skin
tolerability, avoiding safety problems and developing pleasant sensorial properties. Sunscreens, i.e.,
substances able to reflect and/or absorb, at a partial or complete extent, UV radiation are the key
actors in skin protection. They are used to implement the level of primary photoprotection against
UV rays. This means that when they absorb the radiation energy, their molecules pass to an excited
state and successively re-emit energy in other forms (vibrational, rotational, infrared radiation) to
come back to the ground state.

Keywords: Sunburn Protection Factor; formulation; filters stability; nanoparticles

1. Introduction
The role the UV rays play in inducing adverse effects at systemic, ocular and skin level is becoming
more and more evident. In the past, as the UVB radiation was held responsible for immediate and
evident skin damages, such as erythema or sunburns [1] the attention was mainly focused on UVB
protection. However, some biological damages caused by UVB radiation on the DNA of keratinocytes
and by the longer wavelength UVA radiation on the dermis, are asymptomatic. Their effects tend
to accumulate over time and show their mischiefs after many years. The UVB radiation induces
carcinogenesis too. After penetrating the dermis, the UVA radiation causes the release of free radicals
which progressively damage the nuclear DNA, cell membranes, functional and structural protein of
skin cells and causes the onset of elastosis as well as possible cancerous changes.
Moreover, the UVA radiation is the main concomitant cause of skin photosensitization and
phototoxicity [2]. Considering that the incident radiation spectrum is constituted by approximately
95% of UVA radiation, we can easily work out how important is to arrange an appropriate skin
protection strategy also from this thick slice of the solar spectrum, which is particularly dangerous as
cannot be screened by either plastic or glass. As regards the UVC rays portion of the spectrum, they
are extremely harmful but cannot reach the surface of the earth because of the screening action due to
the ozone layer.

Cosmetics 2017, 4, 15; doi:10.3390/cosmetics4020015 www.mdpi.com/journal/cosmetics

Cosmetics 2017, 4, 15 2 of 11
Cosmetics 2017, 4, 15 2 of 11

The efficient
efficientreduction
reductionofofallallharmful
harmful uncontrolled
uncontrolled exposure
exposure to ultraviolet
to ultravioletradiation effects
radiation is one
effects is
of the current problems of the cosmetics industry. In some regions of the world
one of the current problems of the cosmetics industry. In some regions of the world that could be that could be defined
“at high risk”,
defined “at highthisrisk”,
is supported by the actions
this is supported by the ofactions
governments and their public
of governments and theirhealth policy.
public Moreover,
health policy.
the formulation
Moreover, of sunscreen
the formulation of products
sunscreenhas increased
products has and widened
increased andtheir protection
widened range, while
their protection the
range,
information to consumers has become more complete
while the information to consumers has become more complete and clear.and clear.
The result of this increasing attention lead, in the last years, to the development of precise
standards. TheseThese forced
forced the industry to respect manufacturing criteria, for example, of sunglasses sunglasses
and eyeglasses, hats, clothing (children’s suits), umbrellas, shielding paints for automobile windows
and tents. These standards also detail the methods of measurement the protection factors (UVB and
UVA).
UVA). The The Australian
Australian Cancer Council, non-governmental organization organization forfor the
the prevention
prevention of of cancer,
cancer,
has dedicated many pages of its website to illustrate a series of tips and tools to prevent harmful
exposures [3]. In Australia, the strong insolation due to the latitude of the continent adds to the high
solar sensitivity of the inhabitants, mostly light-skinned
light-skinned for for their
their Anglo-Saxon
Anglo-Saxon origin.
origin.
Also in Europe, a growing interest in sun protection developed quickly. In 2006, the European
Commission published the the Recommendation
Recommendation 2006/647/EC
2006/647/EC on on protective
protective efficacy
efficacy of sunscreen
products
products and andrelated
relatedindications
indications of use [4]. This
of use publication
[4]. This was intended
publication to standardize
was intended and simplify,
to standardize and
in Europe,inthe
simplify, way how
Europe, the the
way effectiveness of sun protection
how the effectiveness of sunproducts
protectionis verified
products andis the clarity
verified andof the
label
clarityofofcommercial
the label ofproducts.
commercial products.
According to that Recommendation, the SPF (Sunburn Protection Factor) value must be written
on the label and just eight numerical values could be claimed, claimed, as
as well
well as
as the
the relevant
relevant protection
protection level.
level.
It is
is important
importantto tounderline
underlinethat thatthe
theminimum
minimum suggested
suggested labelled SPF
labelled SPFmust
mustbe 6beand the the
6 and maximum
maximum 50+
(corresponding
50+ (corresponding to a tomeasured
a measured SPF SPF
value ≥ 60).
value Furthermore,
≥ 60). Furthermore,the the
SPFSPF
value must
value be followed
must be followedby the
by
qualitative description (low, medium, high or very high protection)
the qualitative description (low, medium, high or very high protection) (Table 1). (Table 1).

1. SPF
Table 1.
Table SPF classification
classification table.
table.

Protection
Protection LevelLevel SPF Value
SPF Value
Low Low protection
protection 6, 6,
1010
Medium
Medium protection
protection 15,15,
20,20,
2525
High protection
High protection 30,30,4040
Very highhigh
Very protection
protection 50+50+

Finally,
Finally,the
theUVA
UVAprotection
protectionvalue should
value keep
should a precise
keep correlation
a precise with with
correlation the UVB
the protection value
UVB protection
mentioned on the label. The minimum UVA protection should be at least 1/3 of the
value mentioned on the label. The minimum UVA protection should be at least 1/3 of the UVB (e.g., UVB (e.g., a SPF
15 product
a SPF in the UVB
15 product in therange
UVB shall
rangehave
shallahave
UVAaprotection factor of
UVA protection at least
factor of at5).least 5).
Furthermore, the critical wavelength value must be, at least, equal to 370 370 nm.
nm. This means the
limit wavelength at which the area of the section under the integrated optical density curve starting
370 nm
at 290 nm up to 370 nm equals
equals 90%
90% of
of the
the integrated
integrated section
section drawn
drawn between
between 290 nm to to 400
400 nm.
nm. In
other words, the product must be able to absorb enoughenough UV UV radiation
radiation at at longer
longer wavelength
wavelength (UVA).
(UVA).
both requirements
The compliance to both requirements is
is shown
shown onon the
the label
label by
by the
thecircled
circledacronym
acronymUVA UVA(Figure
(Figure1):1):

Figure 1.1.Symbol
Figure Symbolusedused
for for products
products compliant
compliant with
with the the requirement
requirement of UVA of UVA protection
protection and
and minimum
minimum Critical Wavelength
Critical Wavelength of 370 nm. of 370 nm.

Reporting on the label the following warnings for the consumers is also recommended:
Reporting on the label the following warnings for the consumers is also recommended:
• Do not stay too long in the sun, even while using a sunscreen product.
• Keep babies and young children out of direct sunlight.
Cosmetics 2017, 4, 15 3 of 11

• Do not stay too long in the sun, even while using a sunscreen product.
• Keep babies and young children out of direct sunlight.
• Over-exposure to the sun is a serious health threat.
• Reducing the quantity of sunscreen product applied will significantly lower the level of protection.
• Apply (generously) sunscreen products before sun exposure.
• Reapply frequently to maintain protection, and especially after perspiration, swimming
or towelling.

Based on several studies, the International Agency for Research on Cancer of the World Health
Organisation [5] has emphasised the importance of the link between the correct application of sunscreen
products and the efficacy of the sun protection factor claimed. In particular, the frequent re-application
of sunscreen products is crucial. Moreover, in order to reach the protection level indicated by the sun
protection factor, sunscreen products have to be applied in quantities similar to those used for testing,
i.e., 2 mg/cm2 , which equals 6 teaspoons of lotion (approx. 36 g) for the body of one average adult
person. This quantity is by far higher than that usually applied by the consumers. Applying a smaller
quantity of sunscreen product leads to a disproportionate reduction in protection. For example, if the
applied quantity is halved, protection may fall by as much as two-thirds. These considerations have
led to a more cautious and controlled sun exposure and more detailed use recommendations.
The cosmetic industry, especially in the sunscreens field, and the health authorities, active in
this area much more than in other cosmetic fields, quickly follows the evolutionary consumer needs.
The concept of broad spectrum, lasting and safety protections leads in a relentless search for new
technological formulae able to:

(1) Ensure uniformity of skin application, resistance to water, sweat and lately, the abrasive action of
the sand;
(2) Be photo-stable, in order to preserve the UV filters from the decomposition induced by solar
irradiation and, consequently, the loss of efficacy during the period of the consumer exposure;
(3) Reach the right synergic combination targeted for normal skin, sensitive skin and babies
consumers, able to avoid all skin sensitization or photosensitization;

2. Efficacy and Evaluation of UVB Sunburn Protection Factor (SPF)

The SPF is an index of the protection potential of the product from UVB rays. It was globally
adopted and is today written on the labels of all sunscreen products, including also the cosmetic lines
against skin photoaging. For years, in the international context, different methods have coexisted [6–10]
(Table 2).

Table 2. SPF assessment methods before 1994.

Country SPF Method ISSUE DATE

USA * FDA 1978 (‘93)
Australia/NZ AS/NZS 1983
Germany DIN 1984
Japan JCIA 1992
South Africa SABS1557 1992
* First standard method.

In 1994, the COLIPA (European Cosmetic Toiletry and Perfumery Association—now Cosmetic
Europe) issued the European Colipa Method for the assessment of the Sunburn Protection
Factor [11]. After the International SPF Test Method CTFA-SA/Colipa/JCIA 2006 [12], which
included the European, Japanese and South-African measurement systems. In November, 2010
Colipa, in collaboration with ISO (International Organization for Standardization), issued the
ISO 24444:2010—Sun Protection test methods—in vivo determination of the Sun Protection Factor
Cosmetics 2017, 4, 15 4 of 11

(SPF) [13]. This method was adopted by Europe, Australia and New Zealand, India, Canada, South
Africa, Mexico, Chile, Russia, Japan, Mercosur and Asean. Currently, in 2017, there are only two
standard methods for the determination of the Sun Protection Factor: the ISO 24444:2010 (now under
revision) and the US FDA 2011 [14].
The test is performed on subjects belonging to photo-type I, II or III according to the Fitzpatrick
classification (Table 3), on the basis these skin types being more prone to sunburn. The skin colour is
determined by the measurement of the Individual Typology Angle ITA◦ (>28◦ ).

Table 3. Classification of skin types according to Fitzpatrick.

Photo-Type Fitzpatrick Classification

Type 1 always burns, never tans
Type 2 usually burns, tans with difficulty
Type 3 sometimes burns, sometimes tans
Type 4 burns minimally, always tans
Type 5 rarely burns, tans profusely
Type 6 never burns, deeply tans

3. Evaluation of the Sun Product Water Resistance

In December 2005, Colipa published the guidelines for determining the water resistance of a
sunscreen product [15] (Colipa Guidelines for evaluating Sun Product Water Resistance 2005) and, on the
next year, the Colipa recommendation n. 16 on “Water Resistance labelling, 2006” [16]. These suggest
how to evaluate the SPF (using the method ISO 24444:2010) before and after water immersion of the
skin site where the sunscreen product has been applied.
For this purpose, a spa-pool fitted with a water recirculation device is utilised. This contains
water at constant temperature between 27 ◦ C and 31 ◦ C.
For sunscreen products claiming to be ‘water resistant’, the SPF is measured after two 20 min
immersions (40 min immersion in total). While, if they claim to be ‘very water resistant’, four 20 min
each immersions will be required (80 min in total). A sunscreen product can claim to be ‘water resistant’
or ‘very water resistant’ if the SPF value after immersion is equal to more than 50% of the value found
before immersion (90% lower unilateral confidence limit for the mean percentage of water resistance
retention ≥ 50%).
To give an example, a 30 SPF product can claim ‘water resistant’ if it keeps its SPF value higher
than 15 after immersion in water.

4. In Vitro Determination of UVA Photoprotection

In 2007 Colipa issued an in vitro evaluation method of the UVA protection factor and the critical
wavelength [17]. After two subsequent revisions, in 2009 [18] and in 2011 [19], the Colipa method was
substituted by the ISO 24443:2012 method [20]. This is based on the transmittance through a layer of
sunscreen product applied on a standard substrate (PPMA polymethylmethacrylate Plexiglas TM),
before and after controlled UV exposure. The sunscreen sample is exposed to an irradiation dose
proportional to the initial UVA protection factor UVAPF0, calculated from the adjusted absorbance
data of the non-exposed sample.
This method permits to determine the UVA protection factor (UVAPF) of the sunscreen product,
the ratio between the labelled SPF protection factor (which was determined by the above-described
in vivo test), the UVAPF and the critical wavelength.

5. Further In Vitro/In-Vivo Methods

Further testing methods are used for the determination of SPF and UVA protection. The SPF
can be also measured by an in vitro test, which cannot be considered as an alternative to the in vivo
Cosmetics 2017, 4, 15 5 of 11

method. The reason is that there is poor correspondence between the in vivo and in vitro SPF values,
especially for high SPF values and at high content of inorganic filters.
In the past, in order to determine the UVA protection factor, the PPD (persistent pigment
darkening) in vivo test was employed [21]. The method currently used is the ISO 24442:2011 [22].
The drawbacks of the in vivo UVA test are, first of all the poor reproducibility, because of the
difficulty of reading of the induced skin pigmentation. Secondly, the subjects need to be exposed to
UVA rays for very long times and this is not considered ethically correct, while being uncomfortable
for the volunteers.

6. FDA 2011 Final Rule

The FDA (1978) was the first in vivo method created for the evaluation of SPF on informed human
volunteers. It was revised in 1993, 1999 and 2011. The last revision issued on June 17th 2011 by the
Federal Register is very similar to the ISO 24444:2010 method. In fact, both are grounded on the
International Sun Protection Factor (SPF) test method, Colipa, 2006.
The slight differences between the ISO and FDA methods have no influence on the results.
Therefore, the SPF values obtained with the two methods are comparable.
The main differences between the methods are the following:

- the calibration times of the UV source (each 12 months for the FDA, each 18 months for the ISO);
- the reference sunscreen products (P2 for the FDA and P2, P3 or P7 for the ISO);
- progressions of exposure times used.

Furthermore, as regards the labeling of the products, the FDA method establishes that the
maximum SPF value to be reported on the label is 50+.
A “Broad Spectrum” UVA protection can be indicated on the label only for sunscreens having
SPF ≥ 15 and a critical wavelength of at least 370 nm.
The water resistance claims allowed on the label are the following:

• 40 min water resistance followed by the SPF value measured after the immersion
• 80 min water resistance followed by the SPF value measured after the immersion

Lastly, in USA the sunscreen products are not considered cosmetic but over-the-counter
(OTC) products.

7. Australia Sunscreen Standard AS/NZS 2604:2012

Issued in 2012 [23], it indicates ISO 24444 and 24443 as methods for the determination of in vivo
SPF and in vitro UVA protection factor.
Sunscreen products are classified in the following way:
1. Therapeutics sunscreens regulated by TGA (Therapeutic Goods Administration), i.e.,
sunscreen products with SPF ≥ 4 having the primary function of protecting from UV rays and
protective products such as insect repellent (SPF ≥ 4) or skin care products with SPF > 15 having as
secondary function the protection from UV rays.
2. Cosmetic sunscreens regulated by NICNAS (National Industrial Chemicals Notification &
Assessment Scheme), i.e., protective products having the secondary function of protecting from UV
rays (skin care products with SPF ≤ 15 and size < 300 mL, lip balm and lip stick with solar filters,
make-up products with solar filters).
The method AS/NZS 2604:2012 indicates 11 possible SPF values to be reported on the label:
LOW protection: 4-6-8-10
MEDIUM protection: 15-20-25
HIGH protection: 30-40-50
Cosmetics 2017, 4, 15 6 of 11

VERY HIGH protection: 50+

All the products must have on the label the indication “broad spectrum” UVA protection, apart
for colored products with SPF < 30.
The possible water resistance claims to report on the label are:
SPF from 4 to 7: no water resistance properties
SPF from 8 to 14: maximum 40-min water resistance properties
SPF from 15 to 29: maximum 2-h water resistance properties
SPF > 30: maximum 4-h water resistance properties

8. Formulation Solutions
A precise formulation strategy has to be set in order to match with all the described requirements
(SPF, UVA, Critical wavelength, water resistance). Moreover, one should consider other variables, like
the solubility and stability of some UV filters and, being cosmetic items, the sensorial aspects.
Particularly for the high SPF values, the best starting point is the selection of the right combination
of UVB and UVA filters, able to reach the right broad spectrum protection and the best possible stability.
In this phase, the use of a well-known, already tested, formula, the suggestions of the suppliers and/or
the use of a sunscreen simulator freely available online (https://www.sunscreensimulator.basf.com)
are some possible starting approach. Usually, the blending of a high number of UV filters at low
percentage is better than a combination of two or three of them at high percentage, both for safety
concerns and also to achieve a synergic combination of effects. The ideal aim is the highest possible
protection with the minimum possible amount of UV filters. Moreover, a high amount of sunscreen
ingredients is often associated to a bad (greasy or waxy) final perception on the skin. Some good
combinations could be:

(a) Diethylamino Hydroxybenzoyl Hexyl Benzoate and Ethylhexyl Triazone in 3:1 ratio [24];
(b) Octocrylene and Butyl Methoxydibenzoylmethane in a ratio of more or less 3:1 [25];
(c) Octocrylene + Butyl Methoxydibenzoylmethane + Bis-Ethylhexyloxyphenol Methoxyphenyl
Triazine [26];
(d) Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine (Bemotrizinol) + Diethylhexyl Butamido
Triazone + Butyl Methoxydibenzoylmethane (based on our experience, unpublished data).

Moreover, the addition of small amount of inorganic UV filters helps to boost the SPF values,
because solids are able to scatter the UV rays and increase their probability to hit and interfere with
the molecules of ‘chemical’ UV filters.
The use of Butyl Methoxydibenzoylmethane (Avobenzone) is almost essential to reach high UVA
protection, but it has to be adequately stabilized in order to avoid the undesired photo-ketonisation
reaction (Figure 2):
The stabilization of Avobenzone could be reached by using different strategies [28,29]:

(1) The right stabilizers:

• Among other filters (Octocrylene, Polysilicone-15, Methylbenzylidene Camphor, Bemotrizinol, etc.);

• among antioxidants (Pentaerythrityl tetra-di-t-butyl hydroxyhydrocinnamate, Diethylhexyl
Syringylidenemalonate);

(2) Solubility: octocrylene, ethylhexyl and homomenthyl salicylates, to avoid crystal formation;
(3) Avoiding the incompatibility with metal ions, by using chelating agents like Disodium EDTA
(4) Avoiding formaldehyde donors;
(5) The combinations of Avobenzone with inorganic UV filters (this is not allowed in the USA) can
improve the stability of avobenzone by about 10–15% but the inorganic UV filters must be of the
coated type;
 SPF from 8 to 14: maximum 40-min water resistance properties
SPF from 15 to 29: maximum 2-h water resistance properties
SPF > 30: maximum 4-h water resistance properties
Cosmetics 2017, 4, 15 7 of 11
8. Formulation Solutions
A precise formulation strategy has to be set in order to match with all the described
(6) Use polar solvents to inhibit Norrish-Type-I cleavage of Avobenzone (Paraffin is bad, Ethanol
requirements (SPF, UVA, Critical wavelength, water resistance). Moreover, one should consider
is good);
other variables, like the solubility and stability of some UV filters and, being cosmetic items, the
sensorial
This aspects.
important phase requires also some considerations concerning:
Particularly for the high SPF values, the best starting point is the selection of the right
(a) The type
combination ofof
UVB finalandusers.
UVA The useable
filters, of Octocrylene, Ethlylhexyl
to reach the right Methoxycinnamate
broad spectrum protection and andthePABA
best
derivatives
possible stability.isInnot suggested
this phase, theforuse
consumers with sensitive
of a well-known, alreadyskin or forformula,
tested, baby products [30].
the suggestions of
the The
(b) suppliers
market: and/or
Europe, the Japan,useUSA,ofetc.,a similarly
sunscreen
to whatsimulator
happens freely available also
for test methods, online
the
(https://www.sunscreensimulator.basf.com)
number of available sunscreen ingredients areis some possible
different starting
according to theapproach. Usually, the
different legislations. In
blending
USAof(where
a highsunscreen
number of UV filters
products are at lowaspercentage
sold OTC and not is better than a products)
as cosmetic combination the of two or
available
threenumber
of them of at UV
highfilters
percentage, both limited
is extremely for safetyin concerns
comparison andtoalso to achieve
Europe. a synergic
Also their maximum combination
allowed
of effects. The ideal
percentages areaim is thecases
in many highest possible
different protection
(Ethlylhexyl with the minimum
Methoxycinnamate possible
allowed amount
at 10% of UV
in Europe,
filters.
at Moreover,
20% in Japan); a high amount of sunscreen ingredients is often associated to a bad (greasy or
waxy)If final
(c) perception
a water resistanton the skin.
formula Some good
is requested, combinations
the could be:
use of hydrosoluble UV filters (Phenylbenzimidazol
Sulfonic Acid) could be a bad idea;
(a) Diethylamino Hydroxybenzoyl Hexyl Benzoate and Ethylhexyl Triazone in 3:1 ratio [24];
(b) Among
Octocrylene and
filters, theButyl Methoxydibenzoylmethane
selection of inorganic filters is aninincreasing
a ratio of more
trend orforless
the3:1 [25]; of ‘natural’
request
(c) Octocrylene + Butyl Methoxydibenzoylmethane + Bis-Ethylhexyloxyphenol
claims. Titanium dioxide and zinc oxide are the most widely used metal oxides as UV Methoxyphenyl
filters. They
Triazine [26];
are efficient, almost photostable, absorb the UVB and UVA radiations and re-emit them mainly as
(d) Bis-Ethylhexyloxyphenol
visible fluorescence or heat. For their Methoxyphenyl Triazine
chemical-physical (Bemotrizinol)
characteristics, + Diethylhexyl
the surface of the twoButamido
pigments
has toTriazone
be coated+ Butyl
with Methoxydibenzoylmethane
“inert” substances like silica, (based on our
alumina, experience,
stearic acid or unpublished data). If
silicone compounds.
uncoated, TiO2 surface,
Moreover, after UV
the addition absorption,
of small amountemits excited electrons,
of inorganic UV filterswhich
helpscan generate
to boost thefree
SPFradicals,
values,
resulting in oxidative damages into the dermal layers. On the other side, ZnO, if uncoated,
because solids are able to scatter the UV rays and increase their probability to hit and interfere with can
modify the pH of the product as it tends to turn partially into Zn hydroxides, partially releasing OH −
the molecules of ‘chemical’ UV filters.
ions in
Thetheuse
system [31].Methoxydibenzoylmethane
of Butyl Moreover, the coating prevents the agglomeration
(Avobenzone) is almostofessential
particlesto and keephigh
reach the
pigments well dispersed in the system, while improving the stability and UV
UVA protection, but it has to be adequately stabilized in order to avoid the undesired protection efficacy of the
sunscreen product. reaction (Figure 2):
photo-ketonisation

Figure 2. Irreversible photoreactions of Avobenzone [27].

Figure 2. Irreversible photoreactions of Avobenzone [27].

The stabilization of Avobenzone could be reached by using different strategies [28,29]:

Titanium dioxide and zinc oxide are especially used in their ‘nano-sized’ form for many reasons.
(1) nanosize
The The rightdimension
stabilizers:enhances the protection capacity [32]. Moreover, the smaller the particles,
the higher the homogeneity of the layer onto the skin, the better the coverage of the epidermis.
Finally, for particle size of about 35 nm, nanoparticles are big enough to absorb, scatter and reflect
short-wavelength UV radiation while they keep invisible to the longer-wavelength, visible light. In
this way, the sunscreen formulation is transparent to the eyes. The optimum particle size for high UVB
and UVA attenuation but good transparency is between 40 nm and 60 nm [33] (see Figure 3).
 Cosmetics 2017, 4, 15 8 of 11

For all nanoparticles, the special range of dimensions can modify significantly their
physicochemical properties. Such characteristics can increase the uptake and extend or even create new
physico-chemical interactions with biological tissues. The potential toxicity risks are well described in
a lot of studies: The main concern is the production of reactive oxygen species, including free radicals
which will result in oxidative stress, inflammation, and consequent damage to proteins, membranes
and DNA [34]. The access route for nanoparticles to enter the body are: ingestion, inhalation and
through the skin. The oral exposure to nanoparticles as cosmetic ingredient in sunscreens is limited
to accidental ingestion of small fractions of lip products and sun protection products and can be
considered
Cosmetics 2017, 4,to
15be low [35]. 8 of 11

Figure
Figure Effect
3. 3.Effect ofof particle
particle size
size ononthe
theUV
UVattenuating
attenuatingproperties
propertiesofoftitanium
titaniumdioxide.
dioxide.Reduction
Reductionofof
particlesize
particle size moves
moves thethepeak of UV
peak of attenuation to shorter
UV attenuation to wavelengths, while improving
shorter wavelengths, while transparency
improving
(Sligtly modified
transparency from
(Sligtly [36], with
modified frompermission
[36], with from Allured.
permission from Allured.

AsAsfarfarasastitanium
titaniumdioxidedioxideand andzinc zincoxide
oxideareareconcerned,
concerned,thetheDepartment
Department of of
Dermatology,
Dermatology,
Venereology and Allergology of the University of Berlin states
Venereology and Allergology of the University of Berlin states that zinc oxide nanoparticles that zinc oxide nanoparticles
penetrate
penetrate
only intoonly
the into the outermost
outermost layers oflayers
stratum of stratum
corneum, corneum,
furrowsfurrows
and into and theinto the orifices
orifices of the
of the hair hair
follicles
follicles but do not reach the viable epidermis [37]. Moreover, the United
but do not reach the viable epidermis [37]. Moreover, the United States Food and Drug Administration States Food and Drug
Administration
indicated that indicated
nano-scale that nano-scale
titanium dioxidetitanium dioxide
may have mayefficacy
better have betterthanefficacy than while
other filters other filters
lacking
while lacking toxicity. Finally, the scientific European committee has
toxicity. Finally, the scientific European committee has emitted in 2012 and 2013 two opinions emitted in 2012 and 2013 two
opinions concerning the 2 nano-size UV filters [24,38]. SCCS stated that
concerning the 2 nano-size UV filters [24,38]. SCCS stated that the use of these ingredients in the the use of these ingredients
innano-form
the nano-form remains
remains safethe
safe for forhuman
the human health. health.
AtAtthethe moment, the only lack of confidenceconcerns
moment, the only lack of confidence concernsthe thepossibility
possibilityofofintroducing
introducingthesethese
nano-ingredients in cosmetics applied in spray form. This is because
nano-ingredients in cosmetics applied in spray form. This is because of the possible risks of inhalation of the possible risks of
inhalation
during theduring the application
application onto the body, onto high thedose
body,
andhighlong dose and time
residence longofresidence time of in
the nanoparticles thethe
nanoparticles in the vital organs can lead to their dysfunction, and
vital organs can lead to their dysfunction, and the limited toxicological data given by producers.the limited toxicological data
given byThe producers.
second step is the solubilisation of sparing soluble solid UV filters like Avobenzone,
The second
Ethylhexyl Triazone, step isetc. theThis
solubilisation
aspect is often of sparing
neglected soluble
during solid
the UV filters like
formulation Avobenzone,
process, with the
Ethylhexyl
consequence that, during its shelf life, the product slowly decreases its protective capacity with
Triazone, etc. This aspect is often neglected during the formulation process, due tothethe
consequence
precipitation that, duringThe
of filters. its shelf
problemlife, the product
is also slowlyby
magnified decreases its protective
the complexity of thecapacity due to theof
system (presence
precipitation of filters.
solid stabilizer, polymers, The emulsifiers,
problem is also etc.) magnified
and by the by poor,theand
complexity
in some casesof thenot system (presence
correct, of
information
solid stabilizer, polymers, emulsifiers, etc.) and by the poor, and in some
available on the solubility of the filters. Therefore, this step asks for the selection of different polar oils cases not correct,
information available
(usually esters on the solubility
like Ethylhexyl Benzoate,ofDibutylthe filters. Therefore,
Adipate, this step
Diisopropyl asks for
Sebacate the selection
are good of
solubilizers)
different polar oils (usually esters like Ethylhexyl Benzoate, Dibutyl Adipate,
able to keep well dissolved the filters. A suggestion could be to prepare the oil phase of the formula Diisopropyl Sebacate
are good solubilizers)
(without waxy ingredients)able to keep
and put wellit dissolved
in the fridge theinfilters.
orderAtosuggestion
verify the could
stabilitybeofto such
prepare the oil
solutions.
phase of the formula (without waxy ingredients) and put it in the fridge in order to verify the
stability of such solutions.
Among all the above reported requirements, the resistance to water-immersion is today a key
parameter. In general, the main ways for obtaining water or very water resistant effects are the
follows:
- Preparing a fully anhydrous formulation with the addition of film forming polymers;
Cosmetics 2017, 4, 15 9 of 11

Among all the above reported requirements, the resistance to water-immersion is today a key
parameter. In general, the main ways for obtaining water or very water resistant effects are the follows:

- Preparing a fully anhydrous formulation with the addition of film forming polymers;
- Creating w/o emulsions;
- Obtaining a meta-stable o/w emulsion with a low level of emulsifiers, adding, also in this case,
good film forming polymers;

In the first case, the absence of emulsifiers avoids a driver of subtraction of the oil layer from the
skin. Moreover, sunscreens are generally soluble in many (polar) oils and do not reach their limit of
solubility because of the high amount of solvent materials. This formula can be with (25–50%) alcohol
or without it. Nevertheless, all-oil formulae are not the most popular cosmetic form for sun protection,
mainly for sensorial (and cost) reasons.
Water in oil emulsions have the advantage of the difficult removal from the skin surface. When
water has evaporated from (or has been absorbed by) the skin, the emulsifier gets homogeneously
dispersed in the oil phase and there is not enough energy available in the oil + emulsifier layer
to incorporate again water droplets from the environment. Moreover, these systems show a good
compatibility with the skin physiology and allow a normal evaporation of sweat.
One dilemma could be the request of a sprayable emulsion with water resistant efficacy; this is
not easily practicable with w/o emulsion. One possible solution is the stabilization of the emulsion
using a little amount of emulsifiers helped by the introduction of stabilizing polymers (like Acrylates
derivatives). The choice of O/W formula requires, also, the introduction of film formers.

9. Conclusions
The formulation of efficient, up to date, internationally marketed sunscreens is a real challenge
for the formulators. The formulation strategy, even if some guidelines exist in the literature and
in suppliers’ documents, still requires thorough testing and adjustments. Stability of the obtained
performances during time and shelf life and at extreme climates is contemporarily a matter of efficacy
and of consumers’ safety. The objectives of this category of products are challenging and continuously
refined with the progression of medical, physical and chemical knowledge. Indeed, a jungle even for
the expert scientists!

Author Contributions: Nicola Lionetti and Luigi Rigano conceived and designed the lay-out of this paper and
carried out the bibliographic research; Nicola Lionetti and Luigi Rigano analyzed critically the data; Nicola Lionetti
wrote the paper; Luigi Rigano revised it..
Conflicts of Interest: The authors declare no conflict of interest.

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