Formulation Development and Characterization of Oxaprozin Transdermal Patch in A Quality by Design Paradigm

Abstract

Objectives: Oxaprozin is a propionic acid derivative belonging to the Non-Steroidal Ant-Inflammatory Drug (NSAID) class, used to treat inflammation and pain in musculoskeletal conditions. Oral administration of Oxaprozin is associated with limited solubility, gastrointestinal irritation, hepatotoxicity, and extensive first-pass metabolism. The present study was focused on reducing gastric side effects and bypasses first pass metabolism by developing oxaprozin transdermal patch using natural skin permeation enhancers by applying Quality by Design (QBD). Materials and Methods: Oxaprozin transdermal patches were prepared using Eudragit RS 100 as the polymer and solvent evaporation method. A custom experimental design was employed to assess the effect of natural skin permeation enhancers, namely Rosemary oil, limonene, oleic acid. 13 formulations were developed and systematically evaluated for physicochemical properties, drug content uniformity, Ex vivo skin permeation, in vitro drug release, skin irritation, and stability. Results: The optimized formulation exhibited a global desirability value of 0.8352 and contained 700 mg of Eudragit RS 100 with 0.1 mL of Rosemary oil. The optimized patch showed 88.68% ex vivo permeation and 94.56% in vitro drug release over 24 hr. Drug release followed a non-Fickian diffusion mechanism, indicating controlled and sustained release. The Draize skin irritation test confirmed that the formulation was not causing skin irritation. Conclusion: The developed oxaprozin transdermal patch shows promising potential as an alternative to oral treatment. By minimizing gastrointestinal irritation and avoiding first-pass metabolism, the formulation offers enhanced patient adherence and enhanced management of musculoskeletal disorders.