Transdermal drug delivery system: A comprehensive review of innovative strategies, applications, and regulatory perspectives

The transdermal drug delivery system (TDDS) is a very successful and suitable approach for drug delivery because of its advantages over other drug delivery systems. The main advantages of this technique include sustained release, bypassing first-pass metabolism, and enhancing patient compliance. However, the skin is composed of several layers through which the drug must pass through to enter the systemic circulation for therapeutic activity and its limitations include poor skin permeability. Effective TDDS must consider drug properties (molecular weight, solubility, and lipophilicity), vehicle composition, and skin characteristics (hydration, temperature, and regional permeability) to overcome these limitations. Chemical permeation enhancers interfere with the lipid matrix of the stratum corneum, and natural permeation enhancers, including essential oils and terpenes, provide other alternatives. Recently, multiple reservoir patches have been developed for the delivery of multiple active ingredients and electronic TDDS patches for automatic drug release. Despite such advancements, challenges persist in the form of skin irritation, the need for special equipment, and the delivery of large molecules requiring additional study. Future research must aim for the development of hypoallergenic adhesives, the optimization of microneedle safety, and the investigation of new nanocarriers to increase the efficacy of TDDSs and patient outcomes. This review explores the various strategies to enhance drug permeation by TDDS and aims to describe their regulatory requirements according to USFDA guidelines and EMA guidelines as well as their comparison, and highlighted various applications of transdermal drug delivery systems in medicine, patents and clinical trials.