Design and Optimization of Liposomal Diclofenac Sodium Formulations Using Box–Behnken Experimental Design for Controlled Drug Release
DOI:
https://doi.org/10.69980/ajpr.v28i2.700Keywords:
Liposomal Diclofenac Sodium, Box-Behnken Design, controlled release, encapsulation efficiency, sustained drug deliverAbstract
Objective: To optimize liposomal formulations of Diclofenac Sodium for controlled release using a Box-Behnken Design (BBD) to address challenges of poor bioavailability, rapid clearance, and gastrointestinal toxicity associated with non-steroidal anti-inflammatory drugs (NSAIDs).
Methods: Liposomes were prepared via thin-film hydration, with lipid-to-drug ratio, cholesterol content, and sonication time as independent variables. Responses included particle size, polydispersity index (PDI), encapsulation efficiency (EE), and 24-hour drug release. The BBD was employed to evaluate variable interactions and optimize formulation parameters. Physicochemical properties were characterized using Dynamic Light Scattering (DLS), Differential Scanning Calorimetry (DSC), and Transmission Electron Microscopy (TEM). In vitro release kinetics were analyzed using the Korsmeyer-Peppas model.
Results: The optimized formulation (lipid-to-drug ratio 12:1, cholesterol 35%, sonication time 14 min) achieved a particle size of 132.6 ± 3.5 nm, PDI of 0.15 ± 0.01, EE of 88.2 ± 1.5%, and 24-hour drug release of 31.5 ± 1.2%, compared to >90% for free Diclofenac Sodium. DLS, DSC, and TEM confirmed stable, uniform small unilamellar vesicles with minimal drug-lipid interactions. The Korsmeyer-Peppas model indicated anomalous transport (n = 0.62, R² = 0.98). BBD analysis showed significant variable interactions (p < 0.05), validating robust optimization.
Conclusion: The optimized liposomal formulation demonstrated superior encapsulation efficiency and sustained release compared to prior studies, effectively addressing NSAID delivery limitations. Future in vivo studies and active targeting strategies are recommended to confirm therapeutic efficacy and facilitate clinical translation.
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