Transdermal Drug Delivery Systems: Advances, Challenges, And Future Perspectives

Transdermal drug delivery systems (TDDS) represent an innovative and effective method for administering drugs systemically through the skin. These systems offer significant benefits over conventional oral and injectable routes by avoiding hepatic first-pass metabolism and allowing for controlled, sustained drug release. This not only enhances drug bioavailability but also improves patient adherence, particularly in the treatment of chronic conditions. Although the skin’s outermost layer, the stratum corneum, presents a significant barrier, advancements in both passive methods (such as patches) and active techniques (including microneedles, iontophoresis, and electroporation) have broadened the scope of drugs suitable for transdermal delivery. This review examines the core mechanisms involved in transdermal permeation, the anatomy and physiological functions of the skin, and the various pathways through which drugs traverse the dermal layers. It classifies TDDS into passive, active, and emerging hybrid systems, detailing their unique design characteristics, representative examples, and clinical use cases. Additionally, it highlights the major advantages of TDDS, such as user-friendliness, minimized gastrointestinal side effects, and enhanced therapeutic efficiency, while also addressing key challenges like potential skin irritation, limited dosing capacity, and high development expenses. The review concludes by exploring both chemical and physical enhancement strategies that are essential for broadening the applicability of TDDS to a more extensive range of pharmaceutical compounds.