A practical framework for implementing Quality by Design to the development of topical drug products: Nanosystem-based dosage forms

Abstract

Skin has been increasingly recognized as an important drug administration route with topical formulations, offering a targeted approach for the treatment of several dermatological disorders. The effectiveness of this route is hampered by its natural barrier, the stratum corneum (SC), and hence, different strategies have been investigated to improve percutaneous drug transport. The design of nanodelivery systems, aiming at solving skin delivery issues, have been largely explored, due to their potential to revolutionize dermal therapies, improving therapeutic effectiveness and reducing side effects. Apart from nanosystem benefits, the fulfilment of the reproducibility requirements and quality standards still limit their industrial production. The optimization of nanosystem formulation and manufacturing process is complex, usually involving a large number of variables. Therefore, a science- and risk-oriented approach, such as Quality by Design (QbD) will provide a comprehensive and noteworthy knowledge, yielding high quality drug products without extensive regulatory burden. This review aims to set up the basis for QbD development approach, encompassing preliminary and systematic risk assessments, with critical process parameters (CPPs) and critical material attributes (CMAs) identification, of different nanosystems potentially used in dermal therapies.

Keywords: Critical quality attributes; Nanosystems development; Process design; Quality by Design; Quality target product profile; Risk assessment.