Preparation and characterization of sorafenib-loaded microprecipitated bulk powder for enhancing oral bioavailability

초록

The aim of this study was to prepare and evaluate Eudragit-based microprecipitated bulk powder (MBP) formulations to enhance the oral bioavailability of sorafenib. Cationic Eudragit E PO and anionic Eudragit 5100 were selected for MBP preparation. Ursodeoxycholic acid (UDCA)-incorporated MBP was also prepared to study the synergistic effect of UDCA in enhancing the bioavailability of sorafenib. Sorafenib-loaded MBPs were successfully prepared by a pH-controlled precipitation method using an aqueous antisolvent. Submicron-sized particles of MBPs were observed by scanning electron microscopy, and the amorphous form of sorafenib in MBPs was confirmed by powder X-ray diffraction. MBPs of cationic and anionic Eudragits showed different in vitro dissolution and pharmacokinetic profiles in rats. Sorafenib in Eudragit E PO-based MBP (E PO-MBP) was rapidly dissolved at low pH conditions (pH 1.2 and 4.0), but was precipitated again at pH 4.0 within 4 h. Dissolution of sorafenib from Eudragit S100-based MBP (S100-MBP) was high at pH 7.4 and did not precipitate for up to 4 h. After oral administration to rats, all MBPs, compared with powder, improved the oral absorption of sorafenib, with S100-MBP showing 1.5-fold higher relative oral bioavailability than E PO-MBP. Moreover, incorporation of UDCA in S100-MBP (S100-UDCA-MBP) further increased the C-max and oral bioavailability of sorafenib, although the dissolution was not significantly different from that of S100-MBP. Taken together, Eudragit-based MBP formulations could be a promising strategy for enhancing the oral bioavailability of sorafenib.

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