UNIVERZA V LJUBLJANI FAKUKLTETA ZA FARMACIJO
ALJA URBANČEK
DIPLOMSKO DELO
UNIVERZITETNI ŠTUDIJSKI PROGRAM KOZMETOLOGIJA
Ljubljana, 2021
UNIVERZA V LJUBLJANI FAKUKLTETA ZA FARMACIJO
ALJA URBANČEK
STABILIZACIJA KREM ZA ZAŠČITO PRED SONCEM S TITANOVIM DIOKSIDOM IN NASTANEK PICKERING EMULZIJ
STABILIZATION OF SUNSCREENS WITH COMMERCIAL GRADES OF TITANIUM DIOXIDE AS PICKERING EMULSIONS
Ljubljana, 2021
The practical part of this thesis was done as part of my Erasmus youth exchange in Lyon in the academic year 2020/21. All laboratory equipment and working materials were provided by LAGEPP institute as part of Université Claude Bernard Lyon 1under the supervision of co-mentor professor Yves Chevalier, PhD. The theoretical part is a joint effort between my Slovenian mentor professor Mirjana Gašperlin, ScD from the University of Ljubljana, Faculty of Pharmacy and a Host Institution from France.
Acknowledgments
I would like to express my sincere appreciation and gratitude to all teachers I worked with in the past year who inspired, motivated and guided me when I was about to give up.
Hvala vam drage ‘sošolkice’, ki ste mi popestrile in lepšale študijske dni, z mano delile strast do kozmetike ter mi vedno stale ob strani. Hvala ti Jan za vso potrpljenje, tehnično pomoč in spodbudne besede, ki so me gnale naprej. Iskrena hvala draga mami in ati, ker sta mi omogočila, da sta študij in izmenjava v Lyonu postala resničnost.
Statement
I hereby declare that my bachelor thesis is my own original work written under the supervision of professor Mirjana Gašperlin, ScD and co-supervision of professor Yves Chevalier, PhD and has not been submitted before to any institution for assessment purposes.
Alja Urbanček
I TABLE OF CONTENTS
1 INTRODUCTION ... 1
1.1 Sun protection products and skin barrier role ... 1
1.1.1 Ultraviolet light and UV protection factor ... 2
1.1.2 Organic UV filters ... 3
1.1.3 Physical UV filters ... 7
1.2 Pickering emulsions and their stability ... 8
1.2.1 Adsorption of nanoparticles at fluid interfaces... 11
1.2.2 Emulsion type ... 12
1.2.3 Deagglomeration ... 13
2 THE AIM AND CONTEXT OF REPORT ... 14
3 MATERIALS AND METHODS OF EXPERIMENTAL PART ... 15
3.1 Materials ... 15
3.2 Appliances ... 15
3.3 Methods ... 16
3.3.1 Theoretical part ... 16
3.3.2 Practical part ... 17
4 RESULTS AND DISCUSION OF EXPERIMENTAL WORK... 20
4.1 Theoretical part ... 20
4.1.1 Particle size and UV protection of TiO2 ... 20
4.1.2 Safety of titanium dioxide nanoparticles ... 23
4.1.3 Commercially coated rutile titanium dioxide particles... 23
4.2 Practical part-emulsions stabilized with commercial grade of TiO2. ... 30
4.2.1 Emulsions stabilized with commercial T-AVO... 30
4.2.2 Emulsions with stearic and oleic acid coated T-AVO ... 30
4.2.3 Emulsions with 30% n-octadecylphosphonic acid coated T-AVO ... 31
5 CONCLUSION ... 35
6 REFERENCES ... 36
II ABREVIATIONS
MED: minimum erythematous dose OA: oleic acid
O/W: oil in water emulsion SA: stearic acid
SPF: sun protection factor
TEM: transmission electron microscopy TiO2: titanium dioxide
T-AVO: Eusolex® T-AVO commercial titanium dioxide (rutile) coated with silica
T-ECO: Eusolex® T-ECO commercial titanium dioxide (rutile) coated with alumina and simethicone, now renamed to T-2000
T-S: commercial titanium dioxide (rutile) coated with silica and stearic acid UV: ultraviolet light
UVA: ultraviolet light of wavelength between 315 and 400 nm UVB: ultraviolet light of wavelength between 280 and 315 nm UVC: ultraviolet light of wavelength between 100 and 280 nm W/O: water in oil emulsion
III ABSTRACT
The most important step in daily skin care routine is undoubtedly, sunscreen. It is the most powerful tool to protect the skin from environmental stressors, most importantly sun rays.
With the evolving number of different skin conditions, there is an increase in the demand for new innovative approaches to create high-performance sunscreen formulations, for example Pickering emulsions. Sun protection products are mainly emulsions containing UV filters.
Particles are a strong static barrier on the interface between immiscible liquids and therefore almost irreversibly held at the interface, which leads to extreme emulsion stability. As sunscreens contain solid mineral particles, its aim is to use these nanoparticles both as UV blockers and stabilizers of emulsion droplets. The benefit of such technology is the surfactant-free character of the sun protection products.
The experimental part of this thesis is divided in the theoretical and practical part. The theoretical bibliographic analysis of commercial grade particles is based on previous studies about modified TiO2 nanoparticles, where we compared the properties of different coatings.
Commercial titanium dioxide nanoparticles are coated either with silica or alumina and additionally modified with different fatty acids to make them partly wetted by oil. We reviewed results from previous students working with commercial TiO2 named T-AVO, T- ECO and T-S, where different emulsions with commercial practices were prepared and then the stability was evaluated according to the droplet size changes.
In the practical part we prepared Pickering emulsions stabilized with TiO2. The main objectives of scientific research were to investigate, develop and characterize sun protection formulation solely stabilized with titanium dioxide nanoparticles, which not only stabilizes emulsions, but it also works as an UV blocker and absorber. Commercial titanium nanoparticles T-AVO were chemically modified with n-octadecylphosphonic acid to become partly hydrophobic. In the end, modified particles were not lipophilic enough and we could not make stable W/O emulsions therefore only O/W emulsions with short stability were prepared. But we proved that higher quantity of solid particles gives smaller emulsion droplets.
Key words: Pickering emulsions, mineral sunscreens, UV filters, modified TiO2, commercial TiO2 nanoparticles
IV RAZŠIRJEN POVZETEK V SLOVENŠČINI
Najpomembnejši korak vsakodnevne nege kože je krema za zaščito pred soncem, ki zaščiti kožo pred škodljivimi vplivi iz okolja, predvsem sončnimi žarki. Z naraščajočim številom različnih kožnih stanj narašča potreba po inovativnih pristopih ustvarjanja visoko kakovostnih in učinkovitih izdelkov za zaščito pred soncem, kot so na primer Pickering emulzije. Pickering emulzije so namesto površinsko aktivnih snovi stabilizirane s trdnimi delci z različno afiniteto do hidrofobne in hidrofilne faze. Izdelki za zaščito pred soncem so večinoma emulzije tipa olje v vodi ali voda v olju z dodatkom UV filtrov, ki jih v Evropi uvrščamo med kozmetiko. Kozmetični izdelki se uporabljajo na zunanjih delih telesa ali sluznicah, z namenom zaščite, izboljšanja izgleda, negovanja in odišavljenja. Površina kože, na katero delujejo kozmetični izdelki, je zapletena fizikalno-kemijska pregrada, ki preko temnega pigmenta in antioksidanta melanina nudi šibko zaščito pred UV žarki.
Sončno svetlobo sestavlja infrardeče sevanje, vidna in le okoli 10 % ultravijolične svetlobe, ki jo sestavljajo UVA in UVB žarki ter najbolj škodljivo UVC sevanje, ki ga zadrži ozonski plašč. Prevladujejo UVA žarki (90 %), ki prodirajo globlje v kožo in razgrajujejo kolagenska in elastinska vlakna ter so primarno odgovorni za učinke fotostaranja. UVB žarki imajo krajšo valovno dolžino in močnejšo energijo, delujejo v zgornjih plasteh kože, kjer neposredno poškodujejo DNA.
UV filtre delimo v dve glavni skupini, organski in anorganski UV filtri. V Evropi je trenutno dovoljenih 26 organskih kemičnih filtrov in dva fizikalna, cinkov oksid (ZnO) ter titanov dioksid (TiO2). Fizikalni filtri zaradi svoje inertnosti in priljubljenosti postajajo vedno bolj zaželena sestavina, zlasti pri ljudeh z občutljivo kožo. UV žarke tako odbijajo kot absorbirajo in nudijo najboljšo zaščito pri velikosti delcev manjših od 100 nm. Ker so lastnosti posameznih filtrov zelo različne, se za najboljšo zaščito uporabljajo kombinacije več filtrov, ki delujejo sinergistično. Titan je eden najpogostejših elementov na zemlji. in mineral, iz katerega pridobivajo najmanj reaktivno obliko delcev, uporabljenih v kozmetiki, se imenuje rutil. Na trgu lahko najdemo najrazličnejše nanodelce, ki se razlikujejo v zaščitnih slojih in količini le teh na enoto delca.
Namen te diplomske naloge je bil raziskati, razviti in ovrednotiti formulacijo izdelka za zaščito pred soncem, stabiliziranega le s trdnimi nanodelci TiO2. Naloga je razdeljena na
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razširjen teoretični del, pregled različnih komercialno dostopnih UV filtrov na osnovi TiO2
in praktični del, kjer so bile izdelane Pickering emulzije.
Metode, s katerimi zmanjšajo reaktivnost delcev TiO2, a ti še vedno ohranijo sposobnost odbijanje in absorpcije UV svetlobe, so vkapsuliranje z makromolekulami in pritrjevanje na elemente prehodnih kovin. Trdni delci v Pickering emulzijah so močna sterična ovira na meji med nemešajočima tekočinama, saj je potrebna velika moč za odstranitev delcev iz medfaze.
Največja stabilnost emulzije je dosežena pri stičnem kotu 90°. Mineralni filtri v izdelkih za zaščito pred soncem tako poleg UV zaščite služijo tudi kot stabilizatorji, kar omogoča nastanek emulzij brez površinsko aktivnih snovi. Stabilne Pickering emulzije tvorijo delci, katerih velikost je manjša od emulgiranih kapljic. Na stabilnost emulzij vpliva tudi ustrezna formulacija in tehnološki proces izdelave. Upoštevati moramo še adsorpcijo trdnih delcev na kapljice, stabilizacijo kapljic, kinetiko adsorpcije in reološke lastnosti. Nestabilnosti, ki se lahko pojavijo, so sedimentacija, flotacija, flokulacija, koalescenca, Ostwaldova rast kapljic in v skrajnem primeru ločitev faz. Razporeditev trdnih delcev je lahko v eni ali več koncentričnih plasteh, povezava dveh kapljic ali tvorba 3D mreže, ki zgosti emulzijo. Delna močljivost in razporeditev na medfazah je odvisna od površinske napetosti stičnih površin.
Stični kot nam kaže sposobnost močljivosti in določa tip emulzije, nanj pa vpliva tudi izbira posamezne oljne faze.
Literaturo smo iskali po najširši bazi Google Scholar z ustreznimi gesli in filtri. TiO2 v kozmetičnih izdelkih so običajno prekriti s plastjo aluminijevega oksida ali silicijevega dioksida in nato dodatno obdelani z različnimi maščobnimi kislinami, ki dodajo delcem hidrofoben značaj.
Rezultati študije, kjer smo primerjali moč zaščite med različnimi komercialnimi oblikami TiO2, so pokazali, da Eusolex T-AVO, s katerim smo delali v praktičnem delu, nudi najvišji zaščitni faktor. Zelo pogosto nanodelce TiO2 prekrijejo s silicijevim dioksidom, ki daje hidrofilni značaj, ščiti delce pred aglomeracijo in tvorbo radikalov. Komercialni delci, ki jih dobimo po obdelavi s silicijevim dioksidom, so cilindrične oblike in dolžine okoli 45 nm.
Druga pogosta možnost je popolno ali delno prekrivanje nanodelcev TiO2 z aluminijevim oksidom. Proces obdelave je kombinacija kemijske vezave in fizikalne adsorpcije. Tako pridobljeni komercialni delci se zaradi hidroksilnih skupin dobro dispergirajo v vodni fazi.
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Ugotovili smo, da vsi trenutno dostopni komercialni delci, ki smo jih našli na trgu, poleg aluminijevega oksida vsebujejo še dodatno plast ali več različnih makromolekul, ki jim dajejo hidrofoben značaj. Nove možnosti obdelave in zaščite reaktivnih nanodelcev pogosto temeljijo na povezavi trdnih delcev z antioksidanti, npr. yttrium oxide (Y2O3) ali dihidroksi fenil benzimidazol karboksilna kislina. Naslednja možnost pa so polimeri v različnih razmerjih, kot je hitosan.
Ugotovili smo, da je za dobro UV zaščito potrebna dobro definirana in kontrolirana velikost delcev. Za nanodelce TiO2 z najširšim spektrom zaščite so optimalne/najboljše velikosti med 50 in 120 nm. Manjši delci ne le, da puščajo manj belega filma na koži, ampak tudi bolje odbijajo UV žarke, kar pa sicer ne velja za skrajno zmanjšane do velikosti nekaj nm.
Primerjali smo še različne obloge, s katerimi prekrijejo nanodelce za zmanjšanje reaktivnosti in spremljali pojavnost posameznih komercialno dostopnih TiO2 v znanstvenih člankih.
V praktičnem delu smo najprej preoblikovali nanodelce TiO2 z n-oktadecilfosforjevo kislino, ki doda komercialni obliki delcev Eusolex T-AVO prekritih s silicijevim dioksidom delno hidrofoben značaj. Po izračunu količine n-oktadecilfosforjeve kisline, potrebne za 30% prekrivanje delcev, smo izdelali Pickering emulzije z izodecil neopentanoatom kot lipofilno fazo. Uporabili smo različna razmerja oljne in vodne faze (50:50, 70:30 in 30:70 m/m) ter različne postopke homogenizacije; magnetno mešalo, rotor stator homogenizator in ultrazvočno sondo. Komercialni TiO2 T-AVO obdelan z n-okadecilfosforjevo kislino je prvič stabiliziral emulzijo V/O, pred tem smo pri vseh poskusih z omenjenim komercialnim UV filtrom uspešno stabilizirali le O/V emulzije. Emulzije, ki smo jih izdelali, so vsebovale 2 % m/m trdnih delcev. Velikosti kapljic so bile približno 50 µm.
Nato smo z različnimi metodami homogenizacije izdelali še vodne suspenzije z obdelanimi delci T-AVO, ki smo jih nato uporabili za izdelavo emulzij. Opazovali in primerjali smo velikostno razporeditev delcev v vodi in ugotovili, da je pri razbitju agregatov najuspešnejši ultrazvok. Na koncu praktičnega dela smo primerjali še velikost kapljic v emulzijah glede na količino dodanih trdnih delcev. Z večanjem količine trdnih delcev smo zmanjšali velikost kapljic.
Ključne besede: Pickering emulzije, mineralni, UV fitri, obdelani TiO2, komercialni TiO2 nanodelci
1 1 INTRODUCTION
1.1 Sun protection products and skin as protection barrier
According to Regulation EC N°. 1223/2009 on cosmetic products, a cosmetic product is any substance or mixture intended to be used on external parts of the human body (epidermis, hair, nails, lips, external genital organs) or with the teeth and the mucous membranes of the oral cavity. Its sole purpose is non-therapeutic. It is intended to clean, perfume, protect, change the appearance and maintain overall good condition of the described body parts (1).
Sunscreens are commercial cosmetic products that were first introduced in 1930s to protect people from harmful UV light and are now present in many different forms from cosmetically elegant water-based gels, alcohol-based O/W emulsions and sprays to greasy and thick water-resistant formulations for extreme conditions. The main active ingredients are UV filters that are listed in the following chapters along with the testing methods that evaluate their efficacy. Additionally, an endless option of antioxidants, UV stabilizers, emollients, oils, silicones or natural extracts can constitute the formulation, which gives a multi-purpose cosmetic product (2).
Skin as an application site for cosmetic products is a complex physically and chemically protective human organ, consisting of epidermis, dermis and subcutis. Its microbiome has an important immunostimulatory role and together with the reinforced tight junction in stratum corneum it protects us from environmental effects (3). The dark pigment melanin, formed by melanocytes in the basal membrane and transported to keratinocytes, works as a
‘natural sunscreen’ that absorbs UV rays in epidermis. Melanin consists of eumelanin and pheomelanin and since it is capable of free radical scavenging, it can reduce oxidative stress.
It was found eumelanin varies from skin to skin and is more present in dark-skinned people therefore the risk of developing skin cancer is lower although they are still strongly advised to regularly apply sunscreen. On the other hand, there are some positive as well as psychological aspects to be considered such as vitamin D synthesis, aspects connecting UV exposure and human skin (4).
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1.1.1 Ultraviolet light and UV protection factor
Sunlight is electromagnetic radiation composed of approximately 50% infrared, 40% visible and 10% ultraviolet light. UV irradiation has the highest energy and can therefore cause various skin conditions from inflammation, premature aging to cancer. UV is subdivided into UVC (100−279 nm) that is absorbed by ozone in the atmosphere and as such irrelevant to the cosmetics industry, UVB and UVA when it comes to causing harmful effects to skin.
UVC rays have the highest energy and can be absorbed by oxygen molecules in the atmosphere. UVB with shorter wavelengths (280−315 nm) represent 5−10% of total UV light. Due to its high energy and greater intensity, UVB light reacts on the skin surface and does not penetrate deeply into the skin. UVB is mostly absorbed by epidermis and can cause damage directly to DNA, thus working cytotoxic. The remaining 90−95% consists of UVA (315−400 nm) which is mainly responsible for premature skin aging. UVA penetrates deeply into the dermis where it alters collagen and elastin fibers, additionally generating reactive oxygen species therefore damaging DNA molecules. The strength of UVB rays not only varies during the daytime, but also geographically. The UVB rays on the northern hemisphere and nearest to the Equator are the strongest at midday during the summertime.
In contrast, the strength of UVA light does not fluctuate much during the day (4).
What also needs to be pointed out are the harmful effects of short wavelength blue light induced oxidative stress, which can contribute to skin aging and can permanently damage DNA by constant radical formation that, however infrequent, escapes antioxidant defenses although some studies claim it does not overwhelm cellular antioxidant defense itself (4).
Unfortunately, even broad-spectrum sunscreens absorb only part of UVA rays (even though an upper limit of 370 nm is recommended, it is hardly ever obtained in practice) and big part of UVB light escapes (considering the right amount of applied sunscreen). As a result, most cellular damage can actually be induced by the remaining light (5).
Sun protection factor is a number that indicates how much protection a product offers against UVB rays. It was introduced in the mid-twentieth century and is still the most important parameter to quantify the effectiveness of a sunscreen. The evaluation is based on measuring the minimum erythematous dose (MED) - the smallest amount of energy required for
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triggering the erythema in unprotected and protected skin. Later on, the ratio between MED of protected and unprotected skin is defined as SPF value (6).
A recent research has shown that almost 50% of all radicals induced by UV radiation are formed due to UVA and infrared light. As a result, adding antioxidants, different complexes and pigments such as TiO2 or ZnO to sunscreens plays a crucial role in protection of human skin against visual and infrared radiation (7).
UVA protection can be determined with different standards or parameters according to the region of the formulated product. Tests for UVA protection factor range from in vivo to in vitro. In vivo classified are IPD (immediate pigment darkening), PPD (persistent pigment darkening) and UVA protection factor. More desired in vitro ones measure the critical wavelength and absorbance determination. The most common in Europe are in vitro UVA protection factor determination-tested under ISO 24443:2012 standard (8).
1.1.2 Organic UV filters
In Europe there are 26 approved organic UV filters that absorb UV light, either UVA or UVB, some more hydrophobic than other. In Table 1 are listed all the approved organic sunscreens with corresponding properties (1).
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Table 1: A list of organic UV filters with corresponding properties approved by European Union
INCI name of UV filter solubility photo-
stability
other
oil ethanol water
UVA
Diethylamino hydroxybenzoyl hexyl benzoate (9)
white granulate white granulate
++ long lasting protection
Butyl
methoxydibenzoylmethane, avobenzone (10)
yellowish,
crystalline powder
--- most unstable
Terephthalylidene dicamphor sulfonic acid, ecamsule (11)
solid solid ++ L’oréal-group
UV B
Ethylhexyl dimethyl PABA (12) yellow liquid soluble -- safety concern nowadays
PEG-25 PABA (13) yellow
viscous liquid
-
stabilizer of other filters Ethylhexyl salicylate, octisalate
(14)
colourless liquid with floral odour
- weak filter, medium for oil-soluble
filters
Homosalate liquid - in vitro safety concern nowadays
Ethylhexyl methoxycinnamate, octinoxate (15)
solid solid -- anti-inflammatory and antioxidant
activity with possible
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5 Octocrylene (15) colourless thick
liquid
- irritations and allergic reactions
Isoamyl 4-methoxycinnamate, amiloxate (15)
liquid --
4-methylbenzylidene camphor (16)
crystalline powder soluble - possible endocrine disruptor (16)
Camphor benzalkonium methosulfate (17)
white to
yellow solid
+ safety concern nowadays
Phenyl benzimidazole sulfonic acid, ensulizone (18)
white to beige
powder
+
Benzylidene camphor sulfonic acid (19)
powder +
3-benzylidene camphor (20) white
crystalline
+
Polyacryl amidomethyl benzylidene camphor
solid safety concern nowadays (21)
Polysilicone-15 (22) yellow viscous liquid silicon
stabilizer of other filters
silky touch Ethylhexyl triazone, octyl
triazone (23)
powder +++ PABA derivative, very water
resistant, expensive
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UVA and UVB Bis-ethylhexyloxyphenol
methoxyphenyl triazine
yellowish powder ++ one of the best UV filters (24)
Drometrizole trisiloxane liquid ++ L’oréal-group owned (25)
Methylene bis-benzotriazolyl tetramethylbutylphenol (nano)
microfine organic particles poorly dissolves in water or oil
+ ‘hybrid , new generation filter (26)
UVB and UVA II
Benzophenone-3, oxybenzone (27)
pale- yellow crystalline powder
+ Weak absorber
hormonal, photo allergenic effects, possible coral bleaching in high concentration
Benzophenone-4 (28),
Benzophenone-5, sulisobenzone
light yellow powder
+
boost SPF
possible minimal irritation
Tris-biphenyl triazine (nano) (29)
partly soluble white powder
++ new generation UV filter
Phenylene
bis-diphenyltriazine
yellow powder + new generation UV filter (30)
Diethylhexyl butamido triazone, iscotrizinol (31)
very oil soluble ++ water resistant, expensive
7 1.1.3 Physical UV filters
Inorganic sunscreens are materials with high refractive index and work by two different mechanisms. There is a common misconception that fine-particles of physical UV filters only scatter UV light, since the attenuation of UV is a combination of scattering and absorption. They block UV light by light scattering due to their high refractive index and absorb UV rays as nanoparticle with required sizes about 100 nm. High energy rays are then released as lower energy infrared radiation. Sun protection is the key element in preventing premature aging and different skin diseases caused by ultraviolet light. Nowadays, physical sunscreens are gaining in importance. They have gone from obscurity to mainstream ingredients since they are considered safe and inert. They reduce the likelihood of photo- induced toxicity and allergic reactions, thus being more suitable for sensitive skin while providing broad-spectrum coverage. Zinc oxide and titanium dioxide are commercially used as pigments when in micro range, and efficient sun-blockers or absorbers when smaller than 1µm, are together with some iron oxides the only inorganic UV filters (32).
1.1.3.1 Commercial grade titanium dioxide
Titanium is one of the most common elements in the Earth’s crust. There are different minerals used as an ore for titanium dioxide extraction, for example ilmenite, anatase, brookite and rutile, the last one being the most desired in cosmetics because of its highest purity and weaker activity as a photocatalyst than anatase... As high purity is required for all ingredients used in cosmetic products, UV filters are no exception, so there are various standards to ensure that (33).
Nowadays, there are many suppliers or manufacturers offering a wide variety of commercial TiO2 as a UV filter, which is used in sunscreens by cosmetic companies. This wide variety is the result of the increased use of micronized powders and coated powders (the coating can consist of alumina, silica, glycerides, or silicone oil). Depending on the chosen product, it is possible to determine different percentage of active part of the particles (34).
C. Couteau et al. (34) study of commercial grade physical UV filters shows the efficacy of sunscreens SPF (from the least efficient to the best provided SPF): Talc < Titanium dioxide
< Z-Cote < Zinc oxide NDM < Tegosun Z500 < Tegosun Z800 < Zinc oxide neutral < Nanox gel 200 TN < Z-Cote max < Eusolex T < Eusolex T-AQUA < Eusolex T-OLEO < Eusolex
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T2000 < Eusolex T-AVO < Eusolex T-ECO < Eusolex TS. We can see Eusolex T-AVO we experimented with, is one of the most efficient inorganic sunscreens currently available on the market. On the contrary, less popular zinc oxide, regardless of the tested commercial form, showed lower efficacy. The best proven zinc oxide grade is coated with silicone (34).
According to the Cosmetics Legislation, all nano-sized materials (meaning one or more dimensions smaller than 100 nm), need to be listed in INCI ingredient list. The fear and concerns about nano materials raised by part of population has inspired scientists working in the cosmetic industry to develop pleasant formulations with TiO2 particles exceeding 100 nm. It is important to invest in this part of sunscreens since a great deal of emphasis is being placed on eco/green cosmetics, which is becoming extremely popular. For instance, patented T-80, TiO2 based UV filter approved by ECOCERT (35) is such a broad-spectrum sunscreen with aggregates bigger than 209 nm.
1.2 Pickering emulsions and their stability
Pickering emulsions are emulsions of any type, either oil-in-water, water-in-oil or even multiple, stabilized by solid particles, assorted in the interfaces instead of surfactants. They consist of two or more immiscible liquid phases and were named in 1907 when this phenomenon was described by Mr. Pickering although the effect had been recognized by Walter Ramsden four years before. Pickering emulsions can be an efficient alternative since they do not contain surfactants that sometimes cause irritation or allergic reactions. To create a stable emulsion, particles should be smaller than droplets; nanoparticles can stabilize few micrometers diameter droplets and micron-sized particles larger emulsion droplets.
Irreversible particle adsorption at the interfaces results in high stability against coalescence.
A wide range of solid particles can stabilize Pickering emulsions when partial wetting conditions are present as seen in Figure 1 (35).
Figure 1: Pickering emulsion type
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The proper design of formulation and an efficient process that gives even particle-size distribution, are two main requirements to prepare a stable emulsion, otherwise different destabilization might be experienced. The phenomena of particle adsorption, droplet stabilization by adsorbed particles, kinetics of adsorption that influence the emulsification process and rheological properties that control creaming and sedimentation need to be considered during the development of Pickering emulsions (36).
A few different approaches to stabilize Pickering emulsion are shown in Figure 2; dense monolayer of particles on a droplet surface (Figure 2, a), formation of bilayer between droplets (Figure 2, b) and multilayer of particles that make emulsions stable. Higher concentration of particles gives smaller droplets, while the remaining particles in medium start to form 3D network in continuous phase and gelation occurs (Figure 2, d). As viscosity rises, rheological properties of emulsion change, and coalescence is slowed down. Such excess may happen if the emulsification process is not powerful enough or simply too many particles were added. On the other hand, low concentration of particles results in large droplets and the phenomenon of ‘limited coalescence’ may occur (Figure 2, e and f) (36).
Figure 2: Possible mechanisms for droplet stabilization by solid particles: a) dense uniform monolayer of solid particles, b) formation of a bilayer in the contact zone between two droplets, c) multilayer of solid particles, d) 3D network of excess particles, e) two- dimensional network when solid particles concentration is too low to create a round droplet, f) limited coalescence (37)
e
f
10
Stability of emulsion is inversely equivalent to the particle size; smaller particles create denser rigid layer around the droplet. Yet, using too small particles (less than 1 nm) is not recommended since they are too easy to remove from the droplet surface. External factors influencing the wetting, which is a prerequisite for making Pickering emulsion stable, range from additional emulsifiers, electrolytes that lower the surface potential and permit flocculation, to changes of pH (36).
Just as classic emulsion can undergo some instability phenomena depending on droplet size as shown in Figure 3, Pickering emulsions are prone to reversible or irreversible mechanisms of destabilization as well. Instabilities of emulsions could be either reversible such as flocculation, sedimentation, and creaming, or irreversible, for example, coalescence, Ostwald ripening and phase separation. Creaming occurs in O/W emulsions where a layer of excessive oil is present, and sedimentation in W/O case when pure water appears at the bottom (37).
Figure 3: Scheme of emulsion instabilities (38)
Emulsions are thermodynamically unstable but can be kinetically stabilized therefore the formulator must provide stable formulation during the estimated time of use. Stabilization is always relative to observation, so-called arbitrary, and does not have a fixed value. The frequency of collision depends on the particle size, particle concentration, liquid viscosity and temperature (32) (38).
11
1.2.1 Adsorption of nanoparticles at interfaces
Appropriate wetting characteristics of solid material enable a particle to be dispersed into chosen medium. Partial wetting can be explained by different interfacial tensions: solid- water, solid-oil, and oil-water, respectively 𝛾𝑆−𝑊, 𝛾𝑆−𝑂, and 𝛾𝑂−𝑊. Wetting of the solid by oil inside a water medium is achieved when adhesion energy, 𝐸𝑎𝑑ℎ (𝑂/𝑊) is positive and spreading coefficient of oil is negative (35).
The contact angle of a particle (𝜃) is an angle measured between tangent to solid-water surface and tangent to oil-water surface at the point where all three phases come together as seen in Figure 4. It is calculated from Equation 1 a) and b) (35).
Equation 1 a) 𝑐𝑜𝑠(𝜃𝑊) =𝛾𝑆−𝑂−𝛾𝑆−𝑊
𝛾𝑂−𝑊 b) 𝑐𝑜𝑠(𝜃𝑂) =𝛾𝑆−𝑊−𝛾𝑆−𝑂
𝛾𝑂−𝑊
As for molecular emulsifiers, solid particles adsorb as monolayers in Pickering emulsion.
Since the surface of emulsion droplets is curved, the larger part of the particle’s surface is oriented outside. Contact angle, given by the Young’s law (𝜃𝑜 = 𝜋 − 𝜃𝑤), size of the particle and interfacial tension determine the transfer energy of a particle between the bulk phases and the oil-water interface (35). Besides wettability, the choice of the oil influences the contact angle of emulsion, the droplet size and stability (39).
Figure 4: Particle wetting and contract angle (18)
The stability of emulsions is defined by the force needed to remove the adsorbed particle from the interface. Particles on the interface build a strong steric barrier against irreversible fusion of droplets. That is why quite strong force is needed to remove the particle from the surface. The free energy of adsorption is related to the size of the solid (spherical) particles and interfacial tension (35).
12
Maximum stability and the strongest adsorption are gained when the contract angle is 90°.
Larger particle size provides larger contact area therefore larger free energy of adsorption.
However, nanoparticles adsorb strongly as well, and adsorption free energy is always much larger than thermal energy regardless of the size. Even though particles work as emulsifiers, they do not have any surface activity (36).
1.2.2 Emulsion type
Particles mostly wetted by water give oil-in-water emulsions, and particles preferably wetted by oil work the other way around, which brings us to similar analogy as for classical emulsions. Neither too hydrophobic nor too hydrophilic particles would give an emulsion since they would be dispersed only in a favorable medium that is why wetting is the key factor defining the type of emulsion (35).
To be more precise, O/W emulsions are expected when contact angle in water is smaller than 90° (𝜃𝑤 < 90°) (Figure 5). In contrast, W/O emulsions would be anticipated with obtuse contract angle (𝜃𝑤 > 90°) (Figure 5). When the contact angle is close to 90°, the most stable emulsion is reached since the adsorption energy is the highest. Such particles can form either W/O or O/W emulsion, and as a result, phase inversion can be triggered. Phase inversion of Pickering emulsions can also be achieved by using particles with different surface properties, or by altering the proportion of each phase (35).
Figure 5: Contact angle, dependent on the affinity of the particles towards the hydrophobic or hydrophilic phase determines the surface curvature and the emulsion type O/W (left side) or W/O (right side) (37)
13 1.2.3 Deagglomeration
Aggregates and agglomerates, defined according to the following source (40) shown in Figure 6 are two unwanted structures that need to be considered while developing any suspension or sunscreen. But sometimes creating electrical charge on droplets, well controlled aggregates can prevent emulsion from worst instabilities such as Ostwald ripening. Deagglomeration is the process of separation of particles once they are wetted and the agent that allows it adsorbs only at the solid-liquid interface. Deagglomerating agents usually do not affect interfacial tension and are not surface active but aim to stabilize the system with electrostatic forces. In addition, liquid penetration and separation can be enhanced (32).
Figure 6: Agregation of primary particles to agglomerates (40)
14
2 THE AIM AND CONTEXT OF DIPLOMA THESIS
The purpose of the study was to produce Pickering emulsions stabilized only by inorganic UV filter-TiO2 particles. Due to unpredictable situation caused by Covid-19, we decided to dedicate a bigger part of work to the theoretical study of literature and scientific articles. Our experimental part was divided into two parts theoretical and practical.
The aim of the first part was to make an overview of commercially available TiO2 UV filters, compare their coatings and thus new properties, and finally evaluate the frequency of occurrence in literature. We reviewed the literature of all possible TiO2 coatings and focused on commercially available nanosized ones. Our primary source of article search was Google Scholar, where we used different keywords and filters.
The aim of the practical part was to work with commercial grade TiO2 used as UV filters and chemically modify the surface properties of the particles that can stabilize Pickering emulsions. We modified commercial particles with n-octadacylphosphonic acid to make them partly hydrophobic and made Pickering emulsions with them. Such vehicle would allow us to make an efficient, safe sunscreen stabilized only using inorganic UV filters with pleasant organoleptic properties, suitable for the majority of customers… There has been an increase in the number of people with manifold skin pathologies such as rosacea, acne, atopic and dry skin therefore consumers with different skin sensitivities can benefit from this technology.
15 3 MATERIALS AND METHODS
3.1 Materials
Synthetic emollient and skin conditioning agent Isodecyl neopentanoate was used as an oil phase and purified water from the central system of LAGEPP laboratory for a water phase of emulsion. Solid particles for stabilisation of emulsion Eusolex® T-AVO (Titanium dioxide, silica), Merck KGaA (Darmstadt, Germany). n-Octadecylphosphonic acid and dichloromethane were used for surface modification of T-AVO.
Eusolex T-AVO by Merck KGaA is a generic name for nano form TiO2 coated with silica which was used in the experimental part. Physio-chemical characteristics of T-AVO are listed in table 3.
Table 2: Physio-chemical properties of titanium dioxide (41) Characteristic
Chemical formula TiO2
Molar mass 79.9 g/mol Appearance White solid
Odor None
Density 4.23 g/cm3 (rutile) Melting point 1843 °C
Refractive index Rutile: 2.6142 Solubility in water
and organic solvents
Insoluble; due to very low dissociation constant in aqueous systems it can be classified as insoluble under physiological conditions.
3.2 Appliances
• Basic laboratory equipment and glassware
• Rotavapor® Buchi R-114 and waterbath B-480, BUCHI Labortechnik AG, Switzerland
• Vacuum oven
• Ultrasound disperser Hielscher UP400S at 500 W
• Rotor-stator mixer UltraTurrax® device (Ika, Germany)
• Magnetic stirrer
16
• Optical microscope LEICA DMLM with a COLORVIEW camera and displayed using Analysis AUTO software.
• The Mastersizer 3000, Malvern Instruments, UK, a small-angle light scattering instrument measures particle size and particle size distribution based on laser diffraction technique. The scattered light intensity is converted into droplet size by using Mie theory. The instrument measures intensity of light scattered when a laser beam passes through a dispersed sample with different refractive index of the dispersed medium (oil) and dispersing medium (water). Wide range of sizes from 10 nm to 3.5 mm can be measured using a single optical path, which makes it commonly used in industry. One con of the diffraction laser is that it does not differentiate between particle aggregates, floccules or isolated particles (42). The malfunctioning of the instrument during the internship added a supplementary peak in the size distributions due to air bubbles stuck to the windows of the measurement cell. Size distributions had a peak corresponding to the air bubbles of approximately 100 µm size. This artifact came from the contamination of the instrument that repeated washings could not fix.
The optical windows could not be replaced by new ones during the internship. The experimental size distributions were manipulated by removing the peak, corresponding to air bubbles, so the correct results could be obtained despite this trouble.
3.3 Methods
3.3.1 Theoretical part
Firstly, we used Google Scholar to search for articles about different types of TiO2 to emphasise why the nanosized one is needed in sunscreens. We then reviewed the most recent safety reports about the usage of TiO2 in cosmetics.
Secondly, we searched for articles in the Google Scholar database with keywords »coated AND TiO2 AND nanoparticles AND sunscreen« without any filter. Next, we selected articles according to their headlines and left out the ones that did not focus on coated TiO2. The search was done on 30 May 2021. The year was not the only search criteria to obtain the broadest picture of the current development and the use of modified particles in practice.
To present the main properties and differences between various commercially available TiO2
nanoparticles, the descriptive method was used where we categorised the particles by the type of coating and later searched for articles focusing on certain type of modification.
17 3.3.2 Practical part
3.3.2.1 Modification of Eusolex T-AVO with n-octadecylphosphonic acid
Firstly, we grafted Eusolex® T-AVO (Merck) with n-octadecylphosphonic acid (Plasma Chem Gmbh). We used analytical scale to weigh 3.993 g of T-AVO and 0.170 g n- octadecylphosphonic acid, we then dispersed it in 200 mL dichloromethane in 250 ml round flask on magnetic stirrer for 10 minutes (600 rpm). Next dichloromethane was evaporated with a rotatory evaporator Rotavapor® (Buchi) at atmospheric pressure for about 20 minutes, and finally, almost dry powder was dried in vacuum oven at 50 °C for 5 minutes after the vacuum was stabilized. After titanium dioxide particles became partially hydrophobic with n-octadecylphosphonic acid, emulsions were prepared.
Equations 2, 3 below represent quantities of fatty acids used for grafting T-AVO particles and symbols are explained more in detail in Table 4. The quantities of n- octadecylphosphonic acid needed to modify solid nanoparticles are listed in Table 5.
Equation 2: 𝐴𝑠𝑝𝑒𝑐𝑖𝑓𝑖𝑐 𝑓𝑜𝑟 𝑇𝑖𝑂2 = 𝐴
𝑚= 3
𝜌𝑇𝑖𝑂2×𝑅𝑇𝑖𝑂2 = 𝟒𝟕, 𝟐𝟑 𝒎𝟐
𝒈
Equation 3: 𝑚𝑑𝑖𝑠. 𝑎𝑔.=𝑛𝑑𝑖𝑠. 𝑎𝑔.× 𝑀𝑑𝑖𝑠. 𝑎𝑔.
𝑛𝑑𝑖𝑠𝑝𝑒𝑟𝑠𝑖𝑛𝑔 𝑎𝑔𝑒𝑛𝑡
𝑚𝑇𝑖𝑂2 = 𝐴𝑠𝑝𝑒𝑐𝑖𝑓𝑖𝑐 𝑓𝑜𝑟 𝑇𝑖𝑂2
𝑎𝑁𝐴
𝑛𝑑𝑖𝑠. 𝑎𝑔.= 𝐴𝑠𝑝𝑒𝑐𝑖𝑓𝑖𝑐 𝑓𝑜𝑟 𝑇𝑖𝑂2
𝑎𝑁𝐴 × 𝑚𝑇𝑖𝑂2 = ( 2
𝜌𝑇𝑖𝑂2 𝑅𝑇𝑖𝑂2× 1
𝑎𝑁𝐴 × 𝑚𝑇𝑖𝑂2) =
= 47,23𝑚2
𝑔 × 1
20 × 10−9𝑚2× 6.02 × 1023 𝑚𝑜𝑙−1× 𝑚𝑇𝑖𝑂2𝑔
= 𝒎𝑻𝒊𝑶𝟐 × 𝟎, 𝟑𝟗𝟐𝟑 × 𝟏𝟎−𝟏𝟒𝒎𝒐𝒍
18
Table 3: Symbol explanation and values used in equations when calculating the quantity of fatty acid needed to modify T-AVO particles.
unit value meaning
𝐴𝑠𝑝𝑒𝑐𝑖𝑓𝑖𝑐 𝑓𝑜𝑟 𝑇𝑖𝑂2 𝑚2 𝑔
47.28 specific surface of TiO2 particle
A 𝑚2 X surface of TiO2 particle
𝑚𝑇𝑖𝑂2 g X mass of a TiO2 particle
𝜌𝑇𝑖𝑂2 𝑔
𝑚3
4.24 × 106 density 𝑅𝑇𝑖𝑂2 m 10 × 10−9 radius
𝑛𝑑𝑖𝑠. 𝑎𝑔. mol X number of moles of dispersing agent
𝑀𝑑𝑖𝑠. 𝑎𝑔. 𝑔
𝑚𝑜𝑙
X molar mass of dispersing agent 𝑎 𝑚2 20 × 10−20 surface of one molecule of
dispersing agent (fatty acid) 𝑁𝐴 Atoms 6.022 × 1023 Avogadro’s constant
Table 4: Mass of n-octadecylphosphonic acid needed for different coverage of 4g of T-AVO Fraction of covered surface-coverage Mass of acid
4 g of TiO2
(T-AVO)
30 % 0,157 g
100 % 0,525 g
200 % 1,05 g
3.3.2.2 Preparation of emulsion with T-AVO at 30% coverage
We first made four emulsions with a fixed 2% mass of modified T-AVO. The first emulsion 50/50 oil/water (same volume of water and oil phase) made with Ultra-turrax was too viscous. As a result, we increased the volume of aqueous phase in second emulsion to 30/70 oil/water. One such emulsion was prepared with magnetic stirrer and another with Ultra- turrax. We then made the fourth emulsion with Ultra-turrax and higher percentage of oil in the ratio 70/30 oil/water.
19
To measure the size of the droplets with optical microscopy, we diluted (2× dilution) each of the four emulsions since it was too hard to measure the size of the pictures showing overlapping droplets in the original concentrated emulsions. The droplets were measured with optical microscope LEICA DMLM under 20x magnification.
After that the dilution test to determine the type of emulsions was performed. The test is carried out by pouring a few drops of water on top of the emulsion and then its solubility is observed. If the drop of water is dissolved in the emulsion, the dispersing phase is aqueous;
if not, the dispersing phase is hydrophobic and the emulsion is W/O.
We then made another batch of emulsions, but first we separately prepared and evaluated suspensions with 2,0 g of coated T-AVO particles and 28,0 g of purified water. Two different processes were used: magnetic stirrer (200 rpm, 30 minutes) and ultrasound UP400S processor (5 minutes). Suspension homogenized with Ultra-turrax was too foamy after a few minutes therefore we skipped this technique. Particle size distribution of both suspensions was analysed with the Mastersizer 3000.
Finally, Pickering emulsions with different percentage of coated T-AVO were made either with ultrasound UP400S (500 W, 5 minutes), magnetic stirrer (200 rpm, 30 minutes), or vigorous agitation with the Ultra-turrax (22 000 rpm, 10 minutes).
20 4 RESULTS AND DISCUSION
4.1 Theoretical part
4.1.1 Particle size and UV protection of TiO2
Pigmentary size titanium dioxide presents the majority of titanium dioxide in the market. Its outstanding light scattering properties of visible light make it a great whitening agent with required opacity and brightness. Because of its high refractive index of 2.493 for anatase and 2.616 for rutile crystal type, titanium dioxide is used as pigment in different coatings and plastics. Refractive index is a dimensionless ratio between velocity of light in vacuum and velocity of light through certain material. Whereas such whiteness is not desired in sunscreens, transparent particles, described as microfine, micronized, nano-size or ultrafine (typically from 4 nm to 250 nm) were developed in the early 1970s. These terms are more likely to refer to well-defined particle size distribution than the actual size. Not only that, the whitening effect decreases with smaller particles, but the ability to scatter UV light increases.
White residue t decreases since smaller particles poorly scatter visible light. Hence size of the particles is the key factor in determining efficient protective spectrum. It is controlled throughout the whole production, until SPF is measured, and the final product is placed on the market. Formulations require stable, non-agglomerating and reproducible particle size distribution to achieve the desired effects. Nanoparticles provide slightly poorer UVA protection compared to larger, white, and nontransparent ones, thus zinc oxide, which is a better UVA absorber, is sometimes added to formulations. To achieve adequate protection, it is best to use TiO2 primary particles, bigger than 70-80 nm, and ZnO particles over 40 nm (32).
Mineral sunscreens work on two different principles, light scattering and light absorption, which are differently dependent on particle size. In light scattering, responsible for the intensive white pigment effect of TiO2, the particle size ranges between 200 nm and 300 nm, which is approximately half of the wavelength of the visible light. The considered representative length of visible light is 550 nm, which is the most sensitizing wavelength part for a human eye. The results of the formulation show that particle sizes below 100 nm are needed for the best performance of sunscreen products (43).
21
S. Wiechers et al (43) studied TiO2 particles with different median diameters (Figure 7). All the primary particles are of different shapes but make similar sized aggregates therefore no isolated primary nanoparticles can be detected. The study shows that the increased size of primary particles provides lower SPF (Figure 8) but it additionally leaves more of a white cast, and also represents formulation challenges. As a result, decreased sun protection of bigger primary particle cannot be compensated with higher quantity of solid TiO2
nanoparticles. Hydrophobic particles used in the study were made by high temperature hydrolysis of TiO2 in a hydrogen oxygen flame and compared to commercial TiO2 Tego Sun T 805 by Evonik Industries (43).
Figure 7: TEM images of TiO2 nanoparticles produced by flame hydrolysis: a) commercial TiO2 UV filter as a reference; b), c), d), e) different experimental particles with an increasing median size diameter (43)
22
Figure 8: a) particle sizes of commercial and experimental TiO2 UV absorbers produced by flame hydrolysis, b) results of in vitro SPF of commercial TiO2 UV filter and experimental products 1–4 in test formula measured with a transmittance analyzer (43)
Preferred TiO2 particle sizes that absorb UVB as well as UVA are between 50 and 120 nm, absorption of nanoparticles smaller than 20 nm is substantially lowered as seen in Figure 9.
For even better protection in UVA region, it would also be reasonable to consider ZnO particles (Figure 10) (37).
Figure 9: The influence of different particle size of TiO2 on UV absorption (37)
Figure 10: The comparison of TiO2 and ZnO micro-sized particle absorption spectrum (44)
a) b)
-
20 nm-
50 nm-
120 nm23
4.1.2 Safety of titanium dioxide nanoparticles
There are still some uncertainties about the impact of nano particles on human/animal health, but TiO2 used as UV filter in liquid and solid formulations (except sprays) has been recognized as safe and harmless. A major health risk concern is possible lung inflammation, which could lead to the development of cancer when TiO2 nanoparticles are inhaled.
Otherwise studies did not show dermal penetration through undamaged, healthy skin.
Therefore, the main concerns about such nanoparticles could be for workers in production rather than for the consumers (41).
In the recent study carried out in 2020 (45), possible instabilities of TiO2 were observed, since SiO2 coating dissolved during aqueous aging, which could photoactivate unprotected TiO2 nanoparticles.
Demands for nanomaterials which require suffix (nano) is added to the INCI ingredient list, when such material is used in formulation, triggered a search for new inorganic UV filters that do not need this label. Currently there is an ongoing controversy between regulatory requirements, sunscreen performance and aesthetics. From the regulatory standpoint, it might be wise to increase the primary particle size of TiO2 to avoid “nano” labelling in the ingredient list.
4.1.3 Commercially coated rutile titanium dioxide particles
Comparing anatase and rutile TiO2 particles, latter are more desired in cosmetics because of their a few times lower photo-reactivity. To decrease reactivity and aggregation properties of rutile nanoparticles, manufacturers apply several approaches to coat and modify them.
We will mainly focus on available literature about commercially available coated TiO2
nanoparticles used in sunscreens but stay open to new research approaches.
To reduce high photoactivity of small particles, surface modification is often made by raw materials manufacturer. To obtain stable solid particles and prevent photocatalysis, continuous coating film must be dense and inert. It can be modified by inorganic substances such as silica, metal oxides or silicones, or organic (acids) treatments, each giving unique
24
properties… For example, aluminum oxide is the most common choice of metal oxide for inorganic coating. It can enhance the amount of hydroxide groups on the particles and therefore improve dispersibility of particles in aqueous phase and provide more active sites for organic modification further on (46).
Methods to reduce photocatalytic activity of TiO2 nanoparticles while still having desirable scattering and absorption properties as sunscreens, are coating/encapsulating and physical adsorption (47). Encapsulation is the first possible modification with either synthetic or natural macromolecules, and waxes mostly to separate particle from the environment.
Grafting or chemical bonding also gives long-lasting protection with inorganic oxides if a chemical bond is stable against hydrolysis. On the contrary, physical adsorption is more likely to be displaced during stressful production, or other molecules may influence equilibrium conditions (pH or ionic strength change, dilution, additional oil), which can lead to agglomeration (32) (35).
Nowadays, formulators can choose from a wide range of commercially available TiO2
nanoparticles for their products or studies. Unfortunately, there is no clear sum-up which commercial powder best represents the mineral sunscreen in commercial sun protection products and provide the best possible protection (48)(49). This chapter contains some of the most common modified forms of rutile TiO2 nanoparticles used in sun protection products, including alumina, silica, and silicones. In Table 6 the most common commercially available cosmetic grade rutile nanoparticles with corresponding coatings are listed.
25
Table 6 : Commercially available modified rutile TiO2 nanoparticles
Trade name Coating
Eusolex T-S Alumina, Stearic acid
Tayca MT-100 TV Alumina, Stearic acid
Solaveil HTP MBAL Alumina, Stearic acid
Solaveil SpeXtra Polyhydroxystearic acid, Stearic acid, Alumina
Eusolex T-2000 (previous T-ECO) Alumina, Simethicone
UV-Titan M262* Alumina, Dimethicone
Parsol TX Silica, Dimethicone
Eusolex T-EASY Silica, Cetyl Phosphate
Eusolex T-AVO Silica
Eusolex T-AQUA (dispersion) Alumina, Sodium Metaphosphate, Phenoxyethanol, Sodium Methylparaben
T-Lite SF* Aluminum Hydroxide,
Dimethicone/Methicone Copolymer
T-Lite SF-S* Aluminum Hydroxide,
Dimethicone/Methicone Copolymer, Hydrated Silica
Solaveil ST-100 Silica, Polyglyceryl-3 Polyricinoleate, Stearic acid, Aminopropyl Triethoxysilane
Solaveil CT-12W Aluminum Stearate, Alumina, Simethicone Solaveil CT-300 Polyhydroxystearic acid, Aluminum Stearate,
Alumina
Solaveil XT-100 C12-15 Alkyl Benzoate, Polyhydroxystearic acid, Stearic acid, Alumina
Optisol OTP-1 Manganese Dioxide
UV-Titan M111* Alumina
UV-Titan M212* Alumina, Glycerin
*not commercially available anymore
26 4.1.3.1 Silica coated rutile nanoparticles
Silica is frequently used in cosmetics as a thickener, lubricant, or whitening agent, and TiO2
nanoparticles coated with silica combine those characteristics with UV protection. Solely, silica coated particles are hydrophilic, prevented from agglomeration and production of reactive oxygen species with an electron-hole pair. TEM images of silica coated TiO2 are poorly agglomerated, non-spherical, cylindric shape with a length of around 45 nm (33).
Figure 11 summarises an example of study case where silica coated particles of around 100 nm were made in laboratory under different pH levels and temperatures by mixing Tetraethyl Orthosilicate, ethanol, NH4OH and pre-milled TiO2. Themost homogenic silica coating, the best stability in ethanol suspension, stronger absorbance in UV regions thus in vitro protection factor (SPF 42 and UVAPF 39), compared to bare TiO2 were obtained under pH 10 and 80 °C conditions (50).
Figure 11: Synthesis of silica coated TiO2 with an average size of 100 nm (50)
27
4.1.3.2 Alumina and aluminum stearate coated rutile
Alumina is a very common coating for rutile TiO2 nanoparticles to decrease photo-reactivity and improve water-based dispersion stability. Depending on the quantity of aluminium oxide, particles might be partly or completely coated. Study Dong X. et al. shows improved dispersion stability of porous, continuous alumina coated rutile nanoparticles and higher specific surface of particles than bare rutile. This is probably due to the smooth round structure and elevated electrostatic stability that prevents aggregation. Aluminium hydroxide coated rutile TiO2 has the highest specific surface and is optimally stable in the water dispersion at pH 9. Moreover, coating film improves significantly with the increase of aging temperature to 200 °C. The coating process is the synergistic effect between chemical bonding and physical adsorption (51). When additional layer of stearic acid is present, specific surface decreases even more according to the fixed percentage of alumina (See Figure 12) (52).
Figure 12: Surface area of coated rutile particles (52)
Commercial examples of alumina modified filters are listed in Table 6, one of them being alumina and simethicone coated T-ECO. While observing T-ECO under transmission optical microscope, it appears as quite aggregated 50 nm long stick (Figure 13 o)). Depending on the thickness of particles, some are more pungent than others (53). In Figure 13 b), rather low electron dense, somewhat inconsistent layer can be seen around the TiO2 nanoparticles, compared to thicker coating of silica in Figure 13 a) (48). Table 6 shows that currently all readily available commercial TiO2 nanoparticles in the market have additional layer of various macromolecules, from silicones to fatty acids.
Figure 13: o) T-ECO captured by TEM (53), a) T-AVO and b) T-ECO particles under high resolution TEM (48)
O
28 4.1.3.3 Hydrophobic modification of rutile
TiO2 particles modified with stearic acid, or its metal salts have increased compatibility with lipophilic and non-polar phase of cosmetic formulations. Stearate coating provides higher specific surface of TiO2 nanoparticles and can adsorb on bare titania or modified with alumina, as well as prevents them from aggregation. Stearates decrease the photoactivity by self-oxidation in case of oxidative stress. Distribution of stearate coating and its conformation highly depends on hydration since TiO2 has a great affinity towards water.
Earlier studies showed that covalent bond between TiO2 surface and carboxyl group of stearic acid decreased in the presence of water but increased if cations such as aluminium were present on the surface, which is why both modifications are usually present in commercial rutile nanoparticles (52). One example of commercial UV filter modified with aluminum oxide as well as coated with stearic acid is Eusolex T-S, which is completely hydrophobic and 100% covered with the fatty acid (53).
Another way to achieve hydrophobic properties of a particle is silicone coating. Such hydrophobic sunscreen present on the market is Solaveil ST-100 with innovative silane coating technology seen in Figure 14 (54).
Figure 14: Commercialy TiO2 Solaveil ST-100 with silane coating technology (54)
29 4.1.3.4 New possibilities of rutile coating
Many new approaches to reduce photoactivity of TiO2 nanoparticles are being studied. A few of the most recent findings are in favour of coated TiO2 rather than bare and pristine one.
M. Chaki Borrás, et al. modified TiO2 with5% and 10 % w/w Y2O3 by hydrothermal method.
The results showed increased absorbance in UVB and UVA II as well as reduced visible light scattering. Due to reduced photocatalytic activity of coated nanoparticles and antioxidant effect of Y2O3, keratinocytes viability was prolonged in the absence and presence of UV. 10% of yttria coated nanoparticles were the most biocompatible (55).
Another possibility to modify TiO2 is chitosan single step spray-drying pale-yellow powder with a bit of red-shifted absorbance into UVA region and median size of a particle around 2 μm. Chitosan/TiO2 2:1 particleswere more than twice as stable compared to the commercial untreated mixture of anatase and rutile. Along with chitosan being biodegradable and biocompatible polysaccharide, the process is a promising new approach for a sunscreen industry (47).
Most recent study modified TiO2 with an antioxidant dihydroxyphenyl benzimidazole carboxylic acid (Oxisol). Sedimentation was considerably reduced therefore the stabilization of formulation was increased, and most importantly, antioxidant capacity was initiated compared to the one of Oxisol. Consequently, photocatalytic activity decreased, which is a new feature among mineral sunscreens (56).
30
4.2 Practical part - emulsions stabilized with commercial grade of TiO2.
Raw materials such as commercial TiO2 needed for research or the industry come from different suppliers and UV filters usually do not undergo any further modifications except, for example, grafting or coating for research purposes and experiments, but all in all, particles must meet the cosmetic grade requirements (20-150 nm). The majority of commercial particles have already been made partly hydrophobic or hydrophilic and modified by manufacturers. Since our research was the continuation of the work done by previous students, we first collected all the current data in this chapter.
4.2.1 Emulsions stabilized with commercial T-AVO
The literature protocol suggests dispersing 5% TiO2 in affinity phase and starting to make emulsion of 80% of continuous phase that is why the experiment started with this ratio. The aim of research was to find stable emulsion closest to 50/50. Solely, 5% of T-AVO particles stabilize Pickering emulsions O/W quite well, but only a small amount of oil can be dispersed (35% maximum). When bigger quantity of T-AVO is used, the results are uncertain. Figure 15 shows emulsion 20/80 oil/water right after homogenization and well dispersed droplets without aggregates can be seen even after 6 days of storage at 25 °C (53).
Figure 15: Emulsion 20/80 O/W stabilized with T-AVO under optical microscope (53) 4.2.2 Emulsions with stearic and oleic acid coated T-AVO
To create semi-hydrophobic TiO2 particles, T-AVO was modified with stearic and oleic acid.
The study shows that less of it gives better results. Only 10% covered T-AVO with stearic acid succeeded to disperse a larger amount of oil. However, no emulsion remains stable over time (53).
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In another study, series of emulsions were prepared with T-AVO coated by different coverages of stearic acid; 95%, 125%, 150%, 200% and 500% (500% means 5 layers of stearic acid). High steric repulsions and desorption of stearic acid (acid present on the surface of oil phase) lead to different instabilities. It was found that stability and droplet sizes did not depend on the coverage, the desired W/O emulsion could not be obtained and new organic acids were considered (37).
77 % of coated T-AVO with oleic acid could stabilize 50/50 and 30/70 oil/water emulsions for 8 or 9 days, then creaming and coalescence were present. 5% w/w particles well dispersed oil in these emulsions, but the peak around 200 nm indicates excess TiO2 particles are not adsorbed on oil droplets, so a third of quantity should be reduced. Despite the high oil content only O/W emulsions were created with oleic acid. When the quantity of solid particles was reduced from 5% to 1% in 50/50 oil/water emulsion, no excess of particles was seen, but larger droplets were formed. The experiments show that optimal amount of modified T-AVO with oleic acid to stabilize emulsion is slightly less than 2% (37). If we compare modifications with stearic and oleic acid, we discover that destabilization time is the same for both acids. Stearic acid coating was nevertheless better than oleic acid (37).
4.2.3 Emulsions with 30% n-octadecylphosphonic acid coated T-AVO In previous student study, series of emulsions with 2% by mass of coated T-AVO were prepared, namely 30%, 100% and 200% of n-octadecylphosphonic acid. Finally, W/O emulsions were obtained, however 30% coated T-AVO gave inversion emulsions O/W after a few days. The 50/50 and 40/60 oil/water emulsions formulated with 100% and 200% n- octadecylphosphonic acid coated T-AVO remain stable 15 days (37).
The first three emulsion we prepared with 2% of solid particles were O/W type according to dilution test and the fourth W/O. An average droplet size of first 50/50 oil/water emulsion was 48 µm (Figure 16 a), b)), of second 30/70 oil/water 57 µm for magnetic stirrer and 32 µm for Ultra-turrax, and the fourth emulsion 70/30 oil/water was 66 µm (Figure 16 d)).
Ultra-turrax in the 30/70 oil/water resulted droplets half of a size compared to magnetic stirrer and was a method of a choice for further emulsion preparation. On top of 70/30 oil/water emulsion there was an excess of oil. The first three emulsions did not remain stable until the next day.
