Iontophoretic Transdermal Delivery of Anti-Inflammatory Agents: A Review of Recent Advancements

Sanjana R, Vasudeva Rao Pasupulaeti, S Rajarajan, K.Ramesh.

Iontophoretic transdermal delivery systems utilizing silver/silver chloride (Ag/AgCl) electrodes represent an advanced pharmaceutical technology for localized nonsteroidal anti-inflammatory drug (NSAID) administration. This review synthesizes contemporary evidence on the formulation design, physicochemical characterization, biopharmaceutical performance, manufacturing scalability, and clinical efficacy of electrode-based iontophoretic NSAID patches. Iontophoresis enhances transdermal NSAID flux by 3- to 100-fold compared to passive diffusion through electrokinetic drug transport. Optimized polymer matrices combined with reversible Ag/AgCl electrochemistry enable pH-stable, predictable current delivery. Comprehensive characterization via FTIR, DSC, XRD, and validated HPLC confirms formulation stability and drug content uniformity. Recent randomized controlled trials and systematic reviews demonstrate superior analgesic efficacy, improved systemic tolerability, and avoidance of first-pass metabolism compared to oral NSAID administration. Clinical applications include acute post-endodontic pain, musculoskeletal injuries, and osteoarthritis management. Integration of microneedle arrays, stimuli-responsive nanocarriers, and artificial intelligence-driven parameter personalization based on patient skin impedance biometrics is expanding therapeutic potential and addressing inter-individual variability. Iontophoretic NSAID systems are classified as combination products requiring dual pharmaceutical and medical device compliance. Primary limitations include cutaneous adverse effects at elevated current densities and device cost relative to passive alternatives. Silver electrode-based iontophoretic NSAID delivery offers a scientifically robust, clinically compelling platform for precision, patient-centred pain management with substantially reduced systemic exposure and enhanced local tissue targeting.

Keywords –Iontophoresis, transdermal delivery, NSAIDs, Ag/AgCl electrodes, controlled release, combination products.