Transdermal drug delivery approaches for neuropathic pain: Formulation strategies and clinical potential of amitriptyline hydrochloride and meloxicam

Neuropathic pain, including sciatica, is a chronic condition that imposes a significant global burden through mechanisms like dysfunction of the peripheral or central nervous system, sodium channel dysregulation, and neurogenic inflammation, affecting 7-10% of the population globally. Conventional oral Amitriptyline hydrochloride, a tricyclic antidepressant exerting sodium channel blockade along with serotonin/norepinephrine reuptake inhibition, and Meloxicam, a selective cyclooxygenase-2 inhibitor targeting inflammatory prostaglandins, deliver symptomatic relief but are limited by systemic adverse effects such as sedation, dry mouth, gastrointestinal ulcers, and renal impairment. Transdermal drug delivery systems (TDDS) have emerged as a patient-centric alternative, enabling localized, sustained drug release through matrix or reservoir designs with permeation enhancers to overcome the stratum corneum barrier while minimizing first-pass metabolism and plasma fluctuations. This review explores recent advancements in transdermal formulation strategies for Amitriptyline hydrochloride and meloxicam, polymer selection, permeation enhancement methods, and advanced carriers like microneedles and nanostructures tailored for neuropathic pain applications. Additionally, the article highlights the need for further research in this field to develop more effective and targeted therapies for neuropathic pain management.