Fabrication and in vitro-ex vivo Evaluation of Diclofenac Sodium Transdermal Patches for Enhanced Skin Compatibility

Background

Transdermal drug delivery systems provide a sophisticated and patient-compliant strategy for arthritis management by maintaining consistent plasma concentrations, reducing dosing frequency, and minimizing gastrointestinal adverse effects commonly associated with oral nonsteroidal anti-inflammatory drugs.

Aim and Objectives

This study aimed to develop and optimize a controlled-release transdermal system of diclofenac sodium capable of sustaining therapeutic plasma levels, enhancing patient adherence, and improving treatment efficacy compared with conventional oral dosage forms.

Materials and Methods

Diclofenac sodium patches were fabricated using the solvent-casting technique with Hydroxypropyl Methylcellulose (HPMC) and polyvinylpyrrolidone K-30 (PVP K-30) as film-forming polymers, polyethylene glycol 6000 (PEG-6000) as a plasticizer, and Sodium Lauryl Sulfate (SLS) as a permeation enhancer. Nine Formulations (F1-F9) were evaluated for physicochemical parameters including thickness, weight uniformity, folding endurance, drug content, and moisture content. Drug–polymer compatibility and structural integrity were assessed using FTIR, DSC, TGA, and SEM. In vitro release studies were performed in Phosphate buffer (pH 7.4), and kinetic modeling was conducted using zero-order, first-order, and Higuchi equations to elucidate the release mechanism.

Results and Discussion

All formulations displayed satisfactory physicochemical properties with uniform drug distribution and matrix stability. FTIR, DSC, and TGA confirmed the absence of drug–polymer interactions, while SEM micrographs revealed smooth and homogeneous surface morphology. In vitro studies demonstrated sustained release up to 9 hr, with F4, F5, and F6 showing the highest cumulative release (89.54%, 94.14%, and 94.57%, respectively). Drug release followed zero-order kinetics (R²=0.9313–0.989), indicating a concentration-independent, non-Fickian mechanism involving both diffusion and polymer relaxation. Skin irritation testing demonstrated excellent dermal compatibility, with a Primary Irritation Index (PII) < 0.4. According to Draize classification, the patches were non-irritant and safe for dermal application.

Conclusion

Diclofenac sodium transdermal patches formulated with HPMC and PVP K-30 exhibited desirable physicochemical and kinetic properties, with F5 and F6 showing superior sustained-release performance. The non-irritant profile and stable matrix characteristics underscore their potential as effective and safe candidates for transdermal therapy in arthritis management.