Quality-by-Design Approaches in Nano-Enabled Topical and Transdermal Drug Delivery Systems: A Regulatory and Industrial Perspective

Topical and transdermal delivery systems utilizing nanotechnology have a major advantage in enhancing the solubility of drugs, skin penetration and their therapeutic activities but they are complex to develop, changeable in materials and sensitive to scale. Quality-by-Design (QbD) is a scientifically-based approach to these issues, which establishes a clear connection between the Quality Target Product Profile (QTPP), nano-specific Critical Quality Attributes (CQAs), and product performance. Based on the published literature, regulatory guidelines, and topical and transdermal formulations in nano format, this review critically reviews the application of QbD principles, especially with respect to risk assessment tools, Design of Experiments, and control strategies. Regulatively, world bodies are progressively prioritizing on submissions based on QbD with the aim of supporting sound risk management, design space justification, and sound lifecycle control, although some issues of characterization complexity, bioequivalence testing, and in vitro- in vivo correlation continue to persist. Industrial-wise, QbD increases the strength of manufacturing, uniformity in batches, scalability and cost efficiency, reducing development risk, and commercializing. Moving ahead, it is predicted that the combination of artificial intelligence-aided QbD, digital twins, and continuous manufacturing will further enhance predictive development, process perception, and regulatory congruence of nano-enabled topical and transdermal systems of drug delivery.