Sunscreens: photostability, formulation and skin penetration

Kockler, Jutta (2014) Sunscreens: photostability, formulation and skin penetration. PhD thesis, James Cook University.

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Introduction: Sunscreen products, containing UV-filters, are used worldwide to protect from the deleterious effects of sunlight. However, in order to provide this photoprotective function, they should be photostable and remain on the surface of the skin. The photostability of UVfilters, individually and in combination, using different light sources, light intensities, UV-filter concentrations, solvents and formulations has been extensively investigated. Regulations for sunscreen products in Australia, the USA and Europe do not require photostability testing, as per the International Conference on Harmonisation (ICH) Guideline Q1B for new drug substances and drug products. During UV-irradiation on exposure to sunlight, there is potential for chemical UV-filters to degrade by direct photolysis. Chemical UV-filters are also often used in combination with the physical UV-filter, titanium dioxide (TiO₂), increasing the complexity of the system, due to the ability of TiO₂ to cause photocatalytic reactions. In recent years issues have been raised that TiO₂ nano-particles may penetrate through the skin, but no evidence has been found and the Therapeutic Goods Administration (TGA) regards them as safe. However, whether these TiO₂ nano-particles may have an effect on the photostability of chemical UVfilters has not been investigated. The aim of the study was therefore to determine the photostability and skin penetration of a combination of chemical UV-filters with TiO₂, investigating the effect of particle size on photostability.

Methods: Chemical UV-filters, Butyl methoxy dibenzoylmethane (BMDM), Octocrylene (OC) and Benzophenone-3 (B3) were verified for purity by melting point determinations, differential scanning calorimetry (DSC) and high performance liquid chromatography (HPLC). UV-filter identity was confirmed by nuclear magnetic resonance (NMR)-, infrared (IR)- and ultraviolet (UV)-spectroscopy. A reverse-phase HPLC method was developed and validated for the simultaneous determination of BMDM and OC in the presence of their photodegradants. Validation parameters included linearity, accuracy, precision, specificity, sensitivity and robustness. This HPLC method was also employed for the determination of UV-filter B3 during skin penetration studies and to identify photodegradants by liquid chromatography - mass spectroscopy (LC-MS).

Photostability studies of BMDM and OC individually and in combination were undertaken in methanol and a microemulsion. The microemulsion was adapted from a formula in the literature, with xanthan gum added to optimise the viscosity for topical application. Photodegradation profiles of chemical UV-filters in methanol were determined in a photoreactor using a medium pressure mercury lamp as light source and a pyrex glass vessel (λ ≥ 300 nm). Incorporated in a microemulsion, UV-filter photostability was determined in a solar simulator (λ ≥ 290 nm), according to ICH Guideline Q1B. The influence of silica coated TiO₂ (~ 119 nm), uncoated micro- (~ 0.6 μm) and nano-TiO₂ (< 25 nm) on the photostability of both chemical UV-filters was investigated. Degradation kinetics of BMDM and OC separately and in combination were studied in methanol in the photoreactor, using a quartz glass vessel (λ ≥ 200 nm).

Skin penetration of BMDM and OC, incorporated in the microemulsion, was then studied in vitro using porcine ear skin in Franz diffusion cells. Results were compared to the skin penetration of UV-filter B3, which is known to penetrate the skin and cause photoallergic skin reactions. UV-filter concentrations were determined in the receptor fluid, the skin (stratum corneum and viable epidermis/dermis) and the remaining microemulsion on the skin surface using the validated HPLC method. The stratum corneum was separated from the viable epidermis/dermis using the tape stripping method.

Results and Discussion: In methanol, photodegradation of BMDM in the presence of silica coated, micro- and nano-TiO₂ was higher than without TiO₂. In general, OC showed less photodegradation than BMDM. Both, BMDM and OC, followed mixed zero- and first-order degradation kinetics. Photodegradants of both UV-filters were identified by LC-MS and molecular weights were confirmed by Fourier transform - mass spectroscopy (FTMS). Two major photodegradants were found for BMDM. Although in the presence of nano-TiO₂ (pyrex glass), OC recovery was reduced by 38 %, after irradiation through quartz glass, one major photodegradant was identified for OC. The major findings from methanol studies, that nano- TiO₂ causes higher photodegradation than micro-TiO₂ and that BMDM is less photostable than OC, were confirmed in the microemulsion and a reference cream. OC did not degrade in the absence or presence of coated TiO₂ and the lowest OC recovery was determined in the presence of nano-TiO₂ (88 %), while BMDM recovery varied from 0 to 16 %. Irradiated in combination with OC UV-filter BMDM showed a higher recovery (16 %) than irradiated alone (4 %), due to the stabilising effect of UV-filter OC on BMDM via triplet-triplet energy transfer.

Although the combination of BMDM and OC influenced their photostability, skin penetration was not affected by their presence in combination. Generally, BMDM, OC and B3 showed low skin penetration. BMDM and OC were not detected in the receptor fluid after 24 hours and only 0.03 % of B3 was detected. To maintain its photoprotective character, a UV-filter should remain on the surface of the skin or in the stratum corneum. Therefore, the presence of these UV-filters in the viable epidermis/dermis is of interest. As expected B3 showed the highest concentration in this skin compartment (1.09 %), followed by BMDM (0.14 %) and OC with the lowest concentration (0.02 %). Percentages were related to the complete UV-filter content in the microemulsion. This penetration is explained in terms of lipophilicity and molecular vi weight of the UV-filters, with B3 being the least lipophilic molecule with the smallest molecular weight, while OC is the most lipophilic molecule with the largest molecular weight.

Conclusions: Photostability of BMDM and OC, including TiO₂, has been extensively investigated. UV-filters are often used in combinations in sunscreen products to increase their photoprotective effect and to reduce their individual components to minimise toxicity. Although the inclusion of nano-TiO₂ in sunscreen products is regarded as safe in terms of skin penetration, the effect of this physical UV-filter on the photostability of chemical UV-filters is noteworthy. This research presents the first findings on the effect of particle size of TiO₂ on the photostability of chemical UV-filters and is significant because of the potential for the photoprotection of sunscreen products containing these UV-filters, to be compromised.

Item ID: 40698
Item Type: Thesis (PhD)
Keywords: butyl methoxy dibenzoylmethane; high performance liquid chromatography (HPLC); microemulsion; nano-TiO2; octocrylene; particle size; pharmaceutical sciences; photostability; skin cancer prevention; skin cancer; skin disorders; skin penetration; sun creams; sun lotions; sunscreens; titanium dioxide; Ultraviolet filters; ultraviolet radiation; UV filters; UV radiation
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Publications arising from this thesis are available from the Related URLs field. The publications are:

Kockler, Jutta, Oelgemöller, Michael, Robertson, Sherryl, and Glass, Beverley D. (2012) Photostability of sunscreens. Journal of Photochemistry and Photobiology C: Photochemistry Reviews, 13 (1). pp. 91-110.

Kockler, Jutta, Robertson, Sherryl, Oelgemöller, Michael, Davies, Murray, Bowden, Bruce, Brittain, Harry G., and Glass, Beverley D. (2013) Butyl methoxy dibenzoylmethane. In: Brittain, Harry G., (ed.) Profiles of Drug Substances, Excipients and Related Methodology. Elsevier, San Diego, CA, USA, pp. 87-111.

Kockler, Jutta, Motti, Cherie A., Robertson, Sherryl, Oelgemöller, Michael, and Glass, Beverley D. (2013) HPLC method for the simultaneous determination of the UV-Filters butyl methoxy dibenzoylmethane and octocrylene in the presence of their photodegradants. Chromatographia, 76 (23-24). pp. 1721-1727. Item availability may be restricted.

Kockler, Jutta, Oelgemöller, Michael, Robertson, Sherryl, and Glass, Beverley D. (2014) Influence of titanium dioxide particle size on the photostability of the chemical UV-Filters butyl methoxy dibenzoylmethane and ctocrylene in a microemulsion. Cosmetics, 1 (2). pp. 128-139.

Date Deposited: 14 Oct 2015 01:46
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1115 Pharmacology and Pharmaceutical Sciences > 111504 Pharmaceutical Sciences @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920117 Skin and Related Disorders @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 50%
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