Formulation Development of SNRI-Loaded Transdermal Drug Delivery Systems for Chronic Musculoskeletal Pain: A Critical Review

Yadav Abhishek Ramkirat, S Rajarajan, Beny Baby, K Ramesh

Chronic musculoskeletal pain (CMP) is a major global health concern associated with persistent pain, functional disability, and reduced quality of life. Conventional oral pharmacotherapy, including nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and acetaminophen, often presents limitations such as gastrointestinal adverse effects, hepatic toxicity, poor patient compliance, and first-pass metabolism. Serotonin–norepinephrine reuptake inhibitors (SNRIs), particularly duloxetine and venlafaxine, have emerged as effective therapeutic agents due to their dual analgesic and antidepressant actions. However, oral SNRI administration is associated with fluctuating plasma concentrations and systemic side effects.  Transdermal drug delivery systems (TDDS) provide a promising alternative approach for the sustained and controlled delivery of SNRIs through the skin. TDDS bypass hepatic first-pass metabolism, maintain steady plasma drug concentrations, improve bioavailability, reduce dosing frequency, and enhance patient compliance. This review discusses the formulation development of SNRI-loaded transdermal patches, including polymer selection, penetration enhancers, plasticizers, adhesives, and backing membranes. Various preparation techniques such as solvent casting, solvent evaporation, and micro reservoir methods are highlighted. The review also summarizes evaluation parameters including physicochemical characterization, drug content uniformity, in vitro release, ex vivo permeation studies, adhesion testing, and skin irritation assessment. Furthermore, emerging technologies such as, microneedles, iontophoresis, and smart patch systems are explored for enhancing transdermal SNRI delivery. Overall, SNRI-loaded TDDS represent an innovative and effective strategy for chronic musculoskeletal pain management, offering improved therapeutic efficacy, safety, and patient adherence compared with conventional oral therapy.

Keywords –Chronic musculoskeletal pain (CMP), Transdermal drug delivery systems (TDDS), Serotonin–norepinephrine reuptake inhibitors (SNRIs),SNRI-loaded transdermal patches.