Developability profile framework for lead candidate selection in topical dermatology.

Area of Science:

• Dermatology
• Medicinal Chemistry
• Pharmaceutical Sciences

Background:

• Topical dermatology drug development often relies on repurposing or combination therapies, with limited New Chemical Entity (NCE) approvals.
• Topical treatments offer localized delivery, minimizing systemic exposure and adverse events for skin diseases.
• Developing topical NCEs faces unique challenges due to stringent physicochemical and formulation requirements compared to oral drugs.

Purpose of the Study:

• To present a novel framework for de-risking the selection of New Chemical Entities (NCEs) for topical dermatology.
• To identify key physicochemical properties critical for successful topical drug development.
• To establish early-stage assessment methods for solubility, stability, and formulation compatibility.

Main Methods:

• A framework based on four calculated physicochemical properties: molecular weight, clogP, topological polar surface area, and aromatic ring count.
• Assessment of molecular solubility using topical-relevant solvents.
• A 2-day accelerated chemical stability methodology for early-stage evaluation.

Main Results:

• The presented framework aids in identifying suitable NCE candidates for topical formulations.
• Physicochemical properties like molecular weight and topological polar surface area are critical for stratum corneum penetration.
• Solubility and stability in topical excipients are key determinants of formulation success.

Conclusions:

• The proposed framework provides a systematic approach to de-risk NCE selection in topical dermatology.
• Early assessment of physicochemical properties, solubility, and stability is crucial for efficient topical drug development.
• This strategy can accelerate the development of novel topical therapies for skin conditions.