Vehicle Effects on the Rosacea Skin Barrier
June 2021 | Volume 20 | Issue 6 | Original Article | 630 | Copyright © June 2021
Published online May 18, 2021
Zoe Diana Draelos MD
Dermatology Consulting Services, PLLC, High Point, NC
Inflammatory papulopustular rosacea produces sensitive facial skin. Thus, medications designed for rosacea require careful vehicle development to insure optimal drug delivery in an environment suitable for barrier repair.
The objective of this phase 1 study was to elucidate the barrier effects of an investigational topical minocycline anhydrous gel 3% in subjects with inflammatory rosacea.
31 male or female subjects with all complexion types and moderate facial rosacea, defined as 15+ inflammatory facial lesions, were enrolled in this single-site study to evaluate the effects of an investigational topical 3% minocycline anhydrous gel vehicle on skin barrier function; the new topical minocycline gel is an investigational product under development and has completed a phase 2b study in rosacea patients. Following a 30-minute acclimation period, subjects underwent a one-minute transepidermal water loss (TEWL) measurement on the left cheek and triplicate pin probe corneometry measurements from the right cheek. Subjects used the investigational topical 3% minocycline anhydrous gel every evening and returned to the research center at day 1, week 2, and week 4.
30/31 subjects completed the research study. The study medication produced a 23% (P
=0.003) increase in skin hydration at day 1 and maintained the hydration increase with a 22% (P
=0.003) increase at week 2 and a 20% increase (P
=0.001) at week 4. Simultaneously, skin barrier function also improved with an 11% reduction in TEWL at day 1 followed by an 18% reduction in TEWL at week 2 (P
=0.001) and a 28% decrease in TEWL at week 4 (P
<0.001). This improvement in skin barrier was due to a combination of skin healing and the moisturizing properties of the investigational topical 3% minocycline anhydrous gel medication evaluated in this study.
The investigational topical 3% minocycline anhydrous gel decreases TEWL, indicating barrier repair, while increasing corneometry measurements, indicating improved skin hydration. J Drugs Dermatol.
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The vehicle into which a topical medication is placed can either improve or damage the skin barrier. Many topical medications are formulated with simple vehicle designs and generous penetration enhancement to insure minimal vehicle effect and good efficacy. While this approach to topical medication development increases chances for successful statistically significant differentiation of active drug from vehicle in phase III pivotal efficacy studies required for regulatory approval, it does not translate into the best topical formulations for skin disease. This becomes apparent when the drug successfully achieves approval status, but possesses dryness, stinging, burning, and/or itching when prescribed by dermatologists. Even though the drug has proved efficacious, it still is a failed drug if not well tolerated by patients.
One of the most challenging dermatologic conditions for topical formulation is rosacea. Rosacea patients possess sensitive skin characterized by easy flushing/blushing due to vasomotor instability, a damaged skin barrier due to chronic inflammation, and heightened neurosensory awareness leading to noxious sensory stimuli following topical product application.1 These facial tendencies create problems for the formulator who must create an optimal drug delivery vehicle that is aesthetically pleasing and appropriate for the sensitive skin of rosacea. If the vehicle produces barrier damage, it will enhance the inflammation characteristic of papulopustular rosacea leading to worsening of the disease process.
This research examined an investigational topical 3% minocycline anhydrous gel; the new investigational topical gel contains 3% minocycline base formulated in a moisturizing vehicle containing hydrocarbon-based gelling agents that afford occlusive properties to the formulation. This formulation was tested for its ability to improve the epidermal barrier by examining skin transepidermal water loss (TEWL) and corneometry measurements before and after 4 weeks of once-daily application.
MATERIALS AND METHODS
31 male and female subjects 18+ years of age of all Fitzpatrick skin types and complexion types with moderate facial rosacea, defined as 15+ inflammatory facial lesions, were enrolled