INTRODUCTION
The role of the vehicle in topical prescription treatments is to deliver therapeutic concentrations of an active drug to a designated skin target site to support patient adherence and satisfaction, ideally without skin irritation. To achieve a pharmacological effect, the drug must be able to penetrate through the stratum corneum (SC) into the viable epidermis and dermis. The skin barrier is composed of terminally differentiated keratinocyte cells (corneocytes) and lipid lamellae, which prevent the movement of water out of the skin.1,2 Most topical prescription treatments use penetration enhancers, such as propylene glycol, polyethylene glycol, and ethanol, to overcome the barrier properties of the skin by intentionally disrupting lipids in the SC to enhance drug permeability, inducing skin irritation.2,3 For example, ruxolitinib, crisaborole, pimecrolimus, and tapinarof creams contain propylene glycol, mupirocin ointment contains polyethylene glycol, and clobetasol propionate spray contains ethanol.4-9 While they are useful for increasing drug penetration and enhancing drug delivery, these vehicles can also inhibit epidermal repair and contribute to local tolerability issues.10,11
Skin barrier dysfunction is present in atopic dermatitis (AD) and other inflammatory skin diseases, resulting in water loss, penetration of irritants and allergens, and skin microbiome disruption.12 The defective skin barrier of patients with AD is worsened by penetration enhancers, possibly delaying disease resolution. Patients who use topical prescription medications for AD frequently experience exacerbation of stinging, itching, and burning.13 Ideally, these unwanted side effects should be minimized while optimizing topical drug absorption and limiting systemic drug absorption. This highlights the need for prescription topical formulations that maintain and repair the skin barrier function without the use of irritating or sensitizing excipients.14 The effect of a formulation on the skin barrier can be assessed through noninvasive assessments, such as
