Continuous Manufacturing of Diclofenac Sodium Oleogel Using Co-Rotating Twin Screw Process: Formulation Development and Performance Assessment

Purpose: This study focused on the development and optimization of a topical diclofenac sodium oleogel using twin-screw processing (TSP), a continuous manufacturing technology, to overcome limitations of conventional topical formulations. The primary objective was to enhance drug permeation and anti-inflammatory efficacy while enabling scalable, efficient production. Methods: A Box-Behnken Design was employed to optimize processing parameters and lecithin concentration. The oleogel was evaluated for yield, organoleptic properties, homogeneity, texture, viscosity, spreadability, pH, drug content, and in vitro drug release. Advanced characterization techniques included X-ray diffraction (XRD), differential scanning calorimetry (DSC). Preclinical studies assessed skin permeation, irritation potential, and pharmacodynamic effects in vivo, alongside biomarker analysis (TNF-α, IL-6, NFκB p65). Results: The optimized formulation (DOE-TSP-O) exhibited excellent physical attributes, high drug content, and sustained drug release. XRD and DSC analyses confirmed the amorphous nature and compatibility of components. No skin irritation was observed. In vivo studies demonstrated significantly enhanced analgesic and anti-inflammatory effects compared to conventional hydrogels, with marked reductions in TNF-α, IL-6, and NFκB p65 expression. The formulation remained stable for over three months under long-term storage conditions (25 ± 2 °C, 60% ± 5% RH). Conclusion: The DOE-TSP-O formulation represents a promising next-generation topical therapeutic for pain and inflammation, offering superior efficacy and stability. Twin-screw processing enabled scalable, reproducible production, making this a viable approach for advanced topical drug delivery systems.