Transdermal delivery and formulation design of opioids: Where are we now and where are we heading?

Opioids have long been the cornerstone of pain management, predominantly administered via oral and parenteral routes. However, these modalities are frequently limited by systemic adverse effects and low oral bioavailability. Transdermal delivery has therefore emerged as an appealing alternative, exemplified by the successful commercialisation of fentanyl and buprenorphine patches. Despite this progress, the past decades have not seen comparable advances for other opioids including morphine, the clinical gold standard, raising critical questions for researchers and industry alike. In this context, the present review provides an overview of the current opioids explored for transdermal formulation design and examines the underlying translational barriers that have constrained progress. We further discuss emerging strategies and insights that may guide the next generation of transdermal opioid therapeutics.