31/05/2016. SPF expectations for a Formulation. Optimising. SPF Performance. Considering the SPF Expectations Formulations published in ISO Standards

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Jun-14 31/05/2016 Optimising SPF Performance John Staton Dermatest SPF expectations for a Formulation Considering the SPF Expectations Formulations published in ISO Standards SPF Active % Yield Reference 16 10% 1.6 P2 15 6% 2.5 P3 4 8% 0.5 P7 20 13% 1.5 S1 1

Jun-14 Jun-14 Jun-14 31/05/2016 Considering the SPF Expectations Formulations published by Raw Material Suppliers Lotions and creams Considering the SPF Expectations TGA Listings n=77 Ex TGA website : https://www.ebs.tga.gov.au Considering the SPF Expectations USA n=34 Actual SPF Results as determined by test lab Consumer.org Survey 2015 2

SPF Yields Individual Actives at 1% Courtesy BASF Personal Care 2014 Improvements to Sunscreen Formulations TRICK...or... TRAP Manipulating the Spectrum CIE Different wavelengths contributes a different value to accumulate the MED The Effective Spectrum values are used to estimate in vitro SPF 3

Manipulating the Spectrum Playing with polarity of Solvents 10% Improvement Hypsochromic Shift Bathochromic Shift Manipulating the Spectrum In vitro Model Abs SPF Spectrum Breadth Manipulating the Spectrum In vitro Model SPF F 20 SPF UVAPF Minimum 1/3 rd Spectrum Breadth 4

Manipulating the Spectrum Background for curve needed SPF Then... Proportionately Increase Actives Spectrum Breadth Manipulating the Spectrum Examples of Spectral performance + = + = Diffey Spectral Uniformity Index 5

Diffey Spectral Uniformity Index SPF 30 UVAPF/SPF Ratio = 0.334 SUI = 8.9 All SPF 30 UVAPF/SPF SUI 0.251 4.4 0.334 8.9 0.337 7.6 0.377 8.4 0.433 23.3 0.556 17.7 UVAPF/SPF Ratio = 0.433 SUI =23.3 SPF 30 Manipulating the Spectrum Example - Vitamin D Claim Plos One DOI:10.1371/journal.pone.0145509 January 29, 2016 SPF Boosting Additives Ingredient SPF Critical Wavelength Butyloctyl salicylate 12 328 Ethylhexyl methoxycrylene 170 386 c12-15 Alkyl benzoate 1 396 c12-15 A + D + P benzoates 1 394 Diethylhexyl naphthalate 26 352 Caprylic Triglycerides 1 390 Almond Oil 1 363 Mineral Oil 1 392 Novel Actives?? 6

...OR... Novel Actives Pure Oil SPF actually 1 to 2! Oils of Nature O Lenick A.J. Jr. Steinberg D.C. Klein K. LaVay C. Dose Form Influence Difference mostly due to dried down film thickness Dose Form Influence Same Actives! SPF 35 SPF 95 Beeswax Polyamides Castor Oil 7

Synergy from Combinations of Actives SPF 25 30% Actives Ratio FAIL Efficiency 0.86 BASF Sunscreen Simulator https://www.sunscreensimulator.basf.com Synergy from Combinations of Actives SPF 25 30% Actives 12% Actives Ratio FAIL Ratio PASS Efficiency 0.86 Efficiency 2.45 BASF Sunscreen Simulator https://www.sunscreensimulator.basf.com Extending Light Path Refractive Index 1.6 increases light path length of the applied film Concertina Effect 8

Discontinuity of Film Film thickness. Holes in film will let disproportionate amount of light through Film Thickness All 4% ZnO Zinc Oxide Suspension Sunflower Oil only plus plus Hydrophilic Hydrophobic Silica Silica Natural Natural Not Natural Photostability - Excipients and Actives 9

Photostability Example Zinc Oxide - same particle size Dispersions of ZnO Actives Powder Oily Dispersion 45oC 40oC In oily base, predispered more stable than nano size powder mixed in! 30oC Differing ZnO Grades ZnO 17.5% ZnO 25% ZnO 16% ZnO 16% 30 nm Aggregated In vivo SPF 180 nm 180 nm nano In vitro SPF Dispersion Dispersion cctg cctg 10 10 Dispersion Dispersion cctg c-c/c 55 59 Opacity also differs - impacts on pigment colour 10

Insolubility of Actives Crystal Growth Crystal + Agglomeration Example Synergy from the Base Structural Additives Potassium Cetyl Phosphate - liquid crystalline Cetyl Palmitate (and) Sorbitan Palmitate Sorbitan Olivate) - fine emulsion (and) C10-30 Alkyl Acrylates Crosspolymer - Better film Xanthan and other Gums - sit high structure Synergy from the Base NICNAS 3 Colour Secondary Susncreens shade study Light Shade Medium Shade Dark Shade Variation each side of middle shade is no more than 2 SPF units 11

Water Resistant Bases Approaches Water Free = thicker film Water/Oil Emulsions = hydrophobic Film Formers = paint like dried film Repellants = ducks back Water Resistant Actives FDA Permitted Actives World Sunscreen Water Resistance from P2 Reference Excipient Type Sunscreen P3 Reference Sunscreen 4 acid Water Resistant NOT Water Resistant 12

w/o Emulsifiers Polyglyceryl-6 polyricinolate PEG-30 Dipolyhydroxystearate Glyceryl oleate Sorbitan olivate Glyceryl stearate S.E. w/o Example Water Resistance from Film Formers VP/Eicosene copolymer Tricontanyl PVP Polyethylene C10-30 Alkyl acrylate crosspolymer 13

Water Resistance against different Salts P2 Reference Sunscreen Condition Potable Water Hard Water Salt Water Wash Off In vitro 29.8% 26.1% 30.9% Wash Off In vivo 28.5% 4 labs 15% to 40% ISO proposed* To be validated* * Dermatest Submission to ISO TC 217 W G 7 2016 W.R. Resin not fully soluble (hard to see) Physical or Micro Instability Micro spoilage (obvious) Chemical Instability Rub out on skin Skin coloured variant of white cream containing Avobenzone 14

Chemical Instability Formaldehyde donor preservatives destabilise Avobenzone! Changes in Transport and Storage Changes in Transport and Storage In vitro Oil Phase 15

Getting to the Point Synergy from combinations of actives. Manipulate the Spectrum It is necessary to consider Dose Form Influence many points Synergy when from formulating the base. sunscreens Insolubility of Actives Film thickness. Photostability - Excipients and Actives Manipulation of the Spectrum Discontinuity of film. Dispersion plus Synergies of Inorganic are Actives. the Water most Resistance effective from ways Ingredients to Water increase Resistance SPF performance from Emulsion Type Physical Stability. Changes during transport or storage. Acknowledgements George Orban - Formulation Development Manager Craig Dennyson- Senior Analytical Chemist Where to for more Information? thescienceofbeauty.com.a u dermatest.com.au 16