Fabrication, Characterization and Pharmacokinetic Evaluation of Doxorubicin-Loaded Water-in-Oil-in-Water Microemulsions Using a Membrane Emulsification Technique

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Doxorubicin (DOX)-loaded water-in-oil-in-water (W/O/W) microemulsions were produced using a shirasu–porous–glass (SPG) membrane emulsification technique. Soybean oil was used as the oil phase; polyglycerol polyricinoleate (PGPR) or tetraglycerol polyricinoleate (TGPR) was used as the surfactant to stabilize the feed W/O emulsions, while Tween 20 was used in the external water phase to stabilize oil droplets containing water droplets. Increasing the feed pressure from 50 to 90 kPa increased the particle size of W/O/W emulsions, whereas it was decreased by increasing the agitator speed. The smallest particle sizes of multiple emulsions were obtained at the feed pressure of 50 kPa and agitator speed of 350 rpm. Under this set of conditions, the increase in the concentration of PGPR or TGPR showed a decrease in the particle size of DOX-loaded W/O/W emulsions. The optimized formulation comprising of 5% w/v PGPR and 3% w/v Tween 20 in the oil phase and external water phase, respectively, with 0.5% w/v of DOX had a particle size of 0.440±0.007 µm and polydispersity index of 0.220±0.087, which was supported by the transmission electron microscopy image. The formulations showed a sustained release profile in phosphate buffer solution (pH 7.4). The plasma concentrations of DOX after intravenous administration to rats were prolonged and gave approximately 17-fold higher area under the drug concentration–time curve (AUC) compared to free DOX solution. Thus, these results demonstrated that the SPG membrane emulsification technique could be used as a promising technique to prepare W/O/W microemulsions for delivering DOX with sustained release characteristics and better bioavailability.

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