A Topical Marriage Made in Heaven: The Right Active Ingredient Meets the Right Formulator

In this episode of Derms and Conditions, host James Q. Del Rosso, DO, welcomes David Osborne, PhD, a formulation expert behind several dermatologic topicals, to explore what drives topical performance, using dapsone and roflumilast as case studies. They begin by challenging long-held vehicle dogma rooted in mid-20th-century corticosteroid training: the idea that ointments always outperform creams or lotions. They note that with newer solubilizers, stabilizers, and vehicles, those rules don’t consistently hold for products approved in the modern era. They next revisit propylene glycol (PG) as a classic double-edged tool: its ability to dissolve more drug helped create “super-potent” corticosteroid lotions, yet higher PG levels can irritate skin, induce contact allergy, and compromise barrier function. However, they clarify that small amounts may serve as a humectant and offer antimicrobial benefits. They then discuss topical roflumilast’s development to illustrate modern formulation problem-solving: the roflumilast molecule is difficult to dissolve in water and tends to precipitate when water is present. The formulation approach minimized supersaturation (allowing a small solid fraction), leveraged a high purity grade of diethylene glycol monoethyl ether (DEGEE), known under the commercial name Transcutol, to hold the active ingredient drug (roflumilast) in solution in the presence of water, and delivered a highly moisturizing, propylene glycol-free and ethanol-free cream. Use of a unique emulsification approach ensured physical stability even at elevated temperatures while avoiding lipid extraction and additional barrier damage. For topical dapsone, Osborne incorporated pharmaceutical-grade Transcutol (free of ethylene-glycol contaminants) to partition the drug, slow release, and reduce systemic exposure. He emphasizes “topical product metamorphosis”: as water evaporates on skin, the local Transcutol concentration rises, dissolving residual crystals and enhancing delivery, the opposite of older vehicles that left behind residual visible crystals and under-delivered active. They close by looking ahead towards preservative minimalism, microbiome-aware vehicles, and designing drugs intrinsically optimized for cutaneous delivery so the base can remain as inert as possible. Tune in to the full episode to hear the formulation backstories behind roflumilast and dapsone, why PG can both enhance delivery and damage skin barrier integrity and function, how Transcutol and robust emulsifiers can solve solubility and stability hurdles, and pearls you can use tomorrow when selecting vehicles and counseling on tolerability.