A Thesis entitled Evaluating UVB and UVA Boosting Technologies for Chemical and Physical Sunscreens by An Ngoc Hiep Huynh Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Master of Science Degree in Pharmaceutical Sciences Industrial Pharmacy ___________________________________________ Gabriella Baki, Ph.D., Committee Chair ___________________________________________ Jerry Nesamony, Ph.D., Committee Member ___________________________________________ Matthew W. Liberatore, Ph.D., Committee Member ___________________________________________ Dr. Amanda C. Bryant-Friedrich, Dean College of Graduate Studies The University of Toledo May 2020 Copyright 2020 An Ngoc Hiep Huynh This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. An Abstract of Evaluating UVB and UVA Boosting Technologies for Chemical and Physical Sunscreens by An Ngoc Hiep Huynh Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Master of Science Degree in Pharmaceutical Sciences Industrial Pharmacy The University of Toledo May 2020 There are currently 14 organic and 2 inorganic UV filters approved in the United States. Due to coral reef safety concerns, octinoxate and oxybenzone have been banned in Hawaii, Key West, FL and the US Virgin Islands; and octocrylene is also being studied for its potential impact on coral reef safety, leaving 11 organic UV filters as viable options for sunscreen manufacturers – with limitations on their combination. Since consumers are always looking for sunscreens with high SPF and broad-spectrum protection, the need for UVB and UVA protection boosting technologies is greater than ever. In a preliminary study, about two dozen emollients were scanned for their SPF boosting capability with selected organic UV filters. In this study, our goal was to evaluate whether and to what extent the in vitro SPF and broad-spectrum protection of three selected organic UV filters (homosalate, octisalate and avobenzone) and the two inorganic UV filters (zinc oxide and titanium dioxide) can be boosted with three selected emollients (diethylhexyl 2,6- naphthalate, C12-15 alkyl benzoate, and butyloctyl salicylate), and an SPF boosting ingredient (SunSpheresTM). Organic, inorganic and mixed organic/inorganic sunscreens were formulated and tested for stability, viscosity, spreadability (TA.XTPlus texture analyzer), and droplet size; as well as in vitro SPF and broad-spectrum protection iii (LabSphere 2000S), and water resistance. The results show that C12-15 alkyl benzoate provided the highest in vitro SPF out of three emollients tested for the organic sunscreens. However, this ingredient did not form a stable emulsion with our inorganic ingredients, therefore, butyloctyl salicylate was selected to be used for this research project. Titanium dioxide had a higher in vitro SPF value; however, zinc oxide provided broader spectrum protection. Therefore, zinc oxide was selected to be combined with the organic UV filters. We observed an in vitro SPF increase in the case of all sunscreens after exposing the sunscreens to a 20-minute water bath. We believe that the film-former, i.e., polyamide-8 and the drying time contributed to higher SPF values after the water bath. All sunscreens had a shear-thinning behavior, which is typical for creams and lotions. Overall, the organic/inorganic UV filter-based sunscreen containing the SunSpheresTM (CS) performed the best in terms of in vitro SPF, water-resistance, and spreadability. iv Dedicated to my parents, Lanh Huynh and That Nguyen, my lovely sister, Khanh Huynh, and my partner in everything - Vinh Dang. I would not be here without all of your support. v Acknowledgements I would like to acknowledge the faculty at the University of Toledo for sharing knowledge, providing feedback and motivation throughout my journey as an undergraduate and graduate student. I would like to sincerely thank Dr. Gabriella Baki, my professor and research advisor for providing me with all the knowledge and support that I needed. I also would like to thank Dr. Jerry Nesamony, Dr. Matthew Liberatore, Dr. Black Curtis, and Mark Chandler for sharing their knowledge and expertise through my academic journey. I also would like to thank the College of Graduate Studies for their continued financial support throughout my graduate studies. vi Table of Contents Abstract .............................................................................................................................. iii Acknowledgements ............................................................................................................ vi Table of Contents .............................................................................................................. vii List of Tables .......................................................................................................................x List of Figures .................................................................................................................... xi List of Abbreviations ........................................................................................................ xii List of Symbols ................................................................................................................ xiii 1 Introduction ................................................................................................................. 1 1.1 Skin as a Barrier ................................................................................................... 1 1.1.1 Skin as a Barrier Against Ultraviolet Rays ................................................... 4 1.2 Relationship Between Skin Cancer and Sunlight ................................................. 6 1.2.1 Types of Ultraviolet Radiation ...................................................................... 6 1.2.2 How Sunlight Causes Cancer ........................................................................ 2 1.3 Sunscreens ............................................................................................................ 3 1.3.1 Importance of Sunscreen Use ....................................................................... 3 1.3.1.1 Mechanism of Action of Sunscreens and FDA Regulation of UV Filters in the US ....................................................................................................... 5 1.3.2 Sunscreen Protection Claims ........................................................................ 9 1.3.3 SPF Boosting Technologies .......................................................................... 9 vii 1.3.4 UV Filter Combinations in the US.............................................................. 11 1.3.5 Sunscreen Dosage Forms ............................................................................ 12 1.4 Current Concerns Associated with UV Filters ................................................... 12 1.4.1 Organic UV Filters ...................................................................................... 12 1.4.2 Inorganic UV Filters ................................................................................... 14 2 Aims of the Research ............................................................................................... 16 3 Materials and Methods ........................................................................................... 17 3.1 Materials ............................................................................................................. 17 3.1.1 Active Ingredients ....................................................................................... 17 3.1.2 Inactive Ingredients ..................................................................................... 18 3.2 Methods .............................................................................................................. 21 3.2.1 Formulation of Sunscreens ......................................................................... 21 3.2.1.1 Formulation Procedure of Sunscreens without SunSpheresTM ............ 25 3.2.1.2 Formulation Procedure of Sunscreens with SunSpheresTM ................. 25 3.2.2 Stability Testing .......................................................................................... 26 3.2.3 In Vitro SPF Testing and Broad-Spectrum Testing .................................... 26 3.2.4 Water Resistance Testing ............................................................................ 27 3.2.5 Viscosity Testing ........................................................................................ 27 3.2.6 Spreadability Testing .................................................................................. 28 3.2.7 Droplet Size Analysis ................................................................................. 28 4 Results and Discussion ............................................................................................ 29 4.1 Stability .............................................................................................................. 29 4.2 In Vitro SPF Testing ........................................................................................... 30 viii 4.3 Water Resistance Testing ................................................................................... 33 4.4 Broad Spectrum Testing ..................................................................................... 34 4.5 Absorbance and Transmittance .........................................................................