Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v7i3.5444
Abstract
Sorafenib remains clinically relevant in hepatocellular carcinoma (HCC), but its low aqueous solubility, variable oral absorption, and dose-limiting adverse effects continue to restrict formulation performance. Nanoemulsions are attractive lipid-based carriers for poorly water-soluble anticancer agents because they can maintain the drug in a solubilized state, increase interfacial surface area, and support reproducible oral dispersion. This study developed sorafenib-loaded oil-in-water nanoemulsions using a quality-by-design strategy in which oil phase concentration, surfactant/cosurfactant mixture (Smix) concentration, and ultrasonication time were optimized by CCD and response surface methodology (RSM). Twenty experimental runs were evaluated for droplet size, polydispersity index (PDI), zeta potential, entrapment efficiency, and 24 h drug release. Quadratic models described all critical responses with high goodness of fit, with R^2 values of 0.9975 for droplet size, 0.9975 for PDI, 0.9953 for entrapment efficiency, and 0.9802 for 24 h release. Increasing Smix and sonication time reduced droplet size, whereas excessive oil or insufficient Smix increased PDI and broadened the distribution. The desirability-optimized formulation contained 13.8% oil phase, 38.1% Smix, and 7.0 min sonication, producing observed validation values of 110.3 +/- 2.7 nm, PDI 0.176 +/- 0.009, zeta potential -31.8 +/- 0.7 mV, entrapment efficiency 82.4 +/- 1.5%, and 24 h release 84.7 +/- 2.0%. These findings support CCD-RSM as an efficient design framework for balancing nanoscale dispersion, drug retention, and release performance in sorafenib nanoemulsions.
Keywords
sorafenib, nanoemulsion, central composite design, response surface methodology, quality by design, hepatocellular carcinoma, lipid-based drug delivery
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[9] Jacob S, Kather F S, Boddu S H S, et al. Innovations in nanoemulsion technology: enhancing drug delivery for oral, parenteral, and ophthalmic applications[J]. Pharmaceutics, 2024, 16(10): 1333.
[10] Wang X, Anton H, Vandamme T, et al. Updated insight into the characterization of nano-emulsions[J]. Expert Opinion on Drug Delivery, 2023, 20(1): 93-114.
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[13] Priani S E, Fakih T M, Wilar G, et al. Quality by design and in silico approach in SNEDDS development: a comprehensive formulation framework[J]. Pharmaceutics, 2025, 17(6): 701.
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[17] Chen H, Wang R, McElderry J D. Discriminative dissolution method development through an aQbD approach[J]. AAPS PharmSciTech, 2023, 24(8): 255.
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