Development of a novel apixaban-loaded solid self-emulsifying drug delivery system for oral administration: physicochemical characterization and pharmacokinetics in rats

초록

PurposeThe aim of this study was to develop a novel apixaban-loaded solid self-emulsifying drug delivery system (S-SEDDS) to enhance oral bioavailability.MethodsOils, surfactants, and co-surfactants were screened based on the solubility of apixaban to select the most suitable for the preparation of apixaban-loaded liquid SEDDS. Next, 1 mL of the liquid SEDDS was suspended in distilled water (100 mL) and spray-dried with 0.75 g of Aerosil 200 (a mesoporous carrier) using a fluid bed granulator to produce apixaban-loaded S-SEDDS. First, the concentration of Aerosil 200 was optimized. Physiochemical properties were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) to examine the morphology, thermal behavior, and crystallinity of the S-SEDDS, respectively. Additionally, the in vitro dissolution and in vivo bioavailability of the S-SEDDS were investigated and compared with those of the powdered drug.ResultsThe liquid SEDDS consisting of Peceol/Labrasol/Cremophor EL at a volume ratio of 15/35/50 presented the smallest emulsion droplet size among all the prepared formulations. The optimized S-SEDDS2 showed maximum drug solubility. Moreover, the physicochemical findings suggested that the S-SEDDS had a rounded morphology and thermal stability, and that crystalline apixaban was converted to an amorphous form. This formulation showed significant improvements in drug solubility (4-fold), dissolution (5.6-fold), and bioavailability (3.2-fold) compared with apixaban powder.ConclusionS-SEDDSs may be efficiently used to improve the solubility, dissolution, and oral bioavailability of poorly water-soluble drugs, as demonstrated by the apixaban-loaded S-SEDDS.

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