ACKNOWLEDGEMENTS: Medical writing support was provided by Prescott Medical Communications Group (Chicago, IL) with financial support from Ortho Dermatologics | Presented at the Fall Clinical Dermatology Conference • October 17-20, 2019 • Las Vegas, NV SYNOPSIS ◾ Halobetasol propionate (HP) and tazarotene (TAZ) are both effective treatments for psoriasis but are limited by labelling restrictions or potential for adverse events ◾ Recently, positive clinical data on a novel halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ; DuobriiTM) lotion formulation for the treatment of moderate or severe plaque psoriasis have been published1-3 ◾ The unique formulation of HP/TAZ lotion utilizes a technology that allows uniform disposition of both active ingredients simultaneously onto the skin surface and has been developed to be a non-greasy lotion that would be well-liked by patients, help adherence, and normalize epidermal barrier function OBJECTIVES ◾ To detail the unique formulation approach to HP/TAZ lotion development ◾ To assess the absorption and epidermal barrier effects of the novel formulation of HP/TAZ lotion compared to expected individual results with HP and TAZ METHODS Polymeric Emulsion Technology Formulation ◾ HP and TAZ are encapsulated within the same oil droplet together with moisturizing/hydrating excipients (light mineral oil, diethyl sebacate; Figure 1) ◾ Oil droplets (HP/TAZ plus excipients) are uniformly distributed within the oil-in-water emulsion; additional water-soluble moisturizing excipients (sorbitol) are trapped within the 3-D matrix (mesh) ◾ On application, the mesh is uniformly distributed on the skin and instantly breaks upon contact with salts commonly present on skin, allowing for uniform absorption of HP/TAZ FIGURE 1. Oil-in-Water Emulsion Droplet Separated Within a Polymeric Matrix 1,000x Magni�cation 10,000x Magni�cation 15,000x Magni�cation Cryo-Scanning Electron Microscopy Other water-soluble excipients are trapped within the polymeric matrix Other water-soluble excipients are trapped within the polymeric matrix Each oil droplet contains halobetasol and tazarotene plus oil-soluble excipients separated by the three-dimensional matrix. Each oil droplet contains halobetasol and tazarotene plus oil-soluble excipients separated by the three-dimensional matrix. Percutaneous Absorption ◾ Percutaneous absorption studies compared the in vitro dermal deposition of HP/TAZ lotion (polymeric emulsion technology) versus HP 0.05% cream (Ultravate®) and TAZ 0.1% cream (Tazorac®) individually • Approximately 5 mg/cm2 of each formulation was applied to the epidermis of dermatomated human cadaver back tissue (one donor) • After 24 hours, HP or TAZ concentrations were determined with Liquid Chromatography-Mass Spectrometry ◾ Another percutaneous absorption study (same methodology as above) compared the permeability of TAZ in a layered application of TAZ 0.1% cream on top of HP 0.05% cream with that of an application of TAZ 0.1% cream only Epidermal Barrier Function ◾ Skin hydration and epidermal barrier maintenance were assessed through corneometry and transepidermal water loss (TEWL) over 24 hours in healthy female participants with Fitzpatrick Skin Type I-IV • Following a 1-week washout with no moisturizing products, vehicle lotion (0.05 mL) was applied to the volar forearm (other forearm served as control) • Moisture (corneometry; Corneometer®) and skin barrier function (TEWL; Tewameter®) were evaluated • Patient preference to several features (hydrating, moisturizing, skin absorption, aesthetic) of the vehicle lotion were assessed through a questionnaire (18 questions) at the 8-hour evaluation point RESULTS Percutaneous Absorption ◾ The polymeric emulsion technology used to formulate HP/TAZ lotion demonstrated higher percutaneous permeation efficiency of active ingredients into the dermal layers than either HP 0.05% cream (Figure 2A) or TAZ 0.1% cream (Figure 2B) alone FIGURE 2. Dermal Levels Following 24 Hours of Topical Exposure to Halobetasol/ Tazarotene Lotion Versus Halobetasol 0.05% Cream (A) or Tazarotene 0.1% Cream (B) 0% 8% 7% 6% 5% 4% 3% 2% 1% 0% 25% 20% 15% 10% 5% HP 0.01%/TAZ 0.045% Lotion Halobetasol Cream, 0.05% HP 0.01%/TAZ 0.09% Lotion Tazarotene Cream, 0.1% A. Halobetasol Dermal Levels (N=10) P e rc e n t o f A p p lie d D o se ( M e a n ) Epidermis Dermis Receptor B. Tazarotene Dermal Levels (N=10) HP, halobetasol propionate; TAZ, tazarotene. ◾ The advantage of simultaneous and uniform delivery of HP/TAZ using this formulation was apparent when it was shown that simply layering TAZ 0.1% cream onto HP 0.05% cream decreased the percutaneous permeation of tazarotene (Figure 3) FIGURE 3. Cumulative Receptor Phase Levels of Tazarotene Following 24 Hours of Topical Exposure of Layered Tazarotene 0.1% Cream on Top of Halobetasol 0.05% Cream Versus Tazarotene 0.1% Cream Alone (N=8) 0% 0.016% 0.014% 0.012% 0.010% 0.008% 0.006% 0.004% 0.002% 0.018% P e rc e n t o f A p p lie d D o se ( M e a n ± S D ) 0 6 12 18 24 Time (Hours) Halobetasol 0.05% Cream with Tazarotene 0.1% Cream in Upper Layer Tazarotene 0.1% Cream Epidermal Barrier Function ◾ The vehicle lotion formulation provided rapid and sustained increases in skin moisturization (Figure 4) and gradual decreases in TEWL over 24 hours (Figure 5) FIGURE 4. Skin Moisturization Assessment of Vehicle Lotion and Untreated Control Over 24 Hours Using Corneometry (N=30) 25 65 60 55 50 45 40 35 30 70 M e a n S co re s ± S D 0 6 12 18 245 11 17 234 10 16 223 9 15 212 8 14 201 7 13 19 Time (Hours) Vehicle Lotion Untreated Control *All time points except baseline P<0.001 versus untreated control. FIGURE 5. Skin Barrier Assessment of Vehicle Lotion and Untreated Control Over 24 Hours Using Transepidermal Water Loss (TEWL) (N=30) 0 10 5 15 M e a n S co re s ± S D 0 6 12 18 245 11 17 234 10 16 223 9 15 212 8 14 201 7 13 19 Time (Hours) Vehicle Lotion Untreated Control *All time points except baseline P<0.001 versus untreated control. ◾ Most participants (93%-100%; 15 total participants) responded favorably (strongly agree or agree) to all questions asked about the various physical attributes (hydrating, moisturizing, skin absorption, aesthetic) of the vehicle lotion CONCLUSIONS ◾ A fixed combination HP 0.01%/TAZ 0.045% lotion formulation has been developed that utilizes an innovative polymeric emulsion technology and an optimal selection of solvents, emollients, and humectants which is aesthetically pleasing and provides enhanced barrier to the skin ◾ Application of this HP/TAZ formulation resulted in a higher permeation efficiency of both active ingredients compared with application of HP or TAZ cream alone ◾ These results are consistent with data from clinical studies, where HP/TAZ has been shown to provide synergistic activity, with efficacy greater than that which would be predicted from the individual active ingredients3 ◾ Taken together, these results suggest that the unique formulation of HP/TAZ lotion may provide a more effective, predictable, and patient-preferred treatment option than use of separate formulations of HP and TAZ REFERENCES 1. Gold LS, et al. J Am Acad Dermatol. 2018;79(2):287-293. 2. Sugarman JL, et al. J Drugs Dermatol. 2017;16(3):194-201. 3. Kircik LH, et al. J Drugs Dermatol. 2019;18(3):279-284. AUTHOR DISCLOSURES Dr. Emil Tanghetti has served as speaker for Novartis, Ortho Dermatologics, Sun, Lilly, Galderma, AbbVie, and Dermira; served as a consultant/clinical studies for Hologic, Ortho Dermatologics, and Galderma; and is a stockholder for Accure. Dr. Linda Stein Gold has served as investigator/consultant or speaker for Ortho Dermatologics, LEO, Dermavant, Incyte, Novartis, AbbVie, and Lilly. Dr. James Del Rosso has served as a consultant, investigator, and speaker for Ortho Dermatologics. Dr. Stefan Weiss has served as consultant, speaker, advisor or research honoraria from AbbVie, Ortho Dermatologics, Jansen Biotech, Dermira, Almirall, Brickell Biotech, DermTech, and Scynexis. Dr. Tina Lin is an employee of Ortho Dermatologics. Mr. Arturo Angel and Dr. Radhakrishnan Pillai are employees of Bausch Health Americas Inc. Optimized Formulation for Topical Application of a Fixed Combination Halobetasol/Tazarotene Lotion Using Polymeric Emulsion Technology Emil A Tanghetti, MD1; Linda Stein Gold, MD2; James Q Del Rosso, DO3; Stefan Weiss, MD4; Tina Lin, PharmD5; Arturo Angel, BS6; Radhakrishnan Pillai, PhD6 1Center for Dermatology and Laser Surgery, Sacramento, CA; 2Henry Ford Hospital, Detroit, MI; 3JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV; 4Direct Dermatology, Palo Alto, CA; 5Ortho Dermatologics, Bridgewater, NJ; 6Bausch Health Americas, Inc, Petaluma, CA