Purpose: Sorafenib is an orally applicable anticancer drug, but has poor aqueous solubility, leading to low oral bioavailability. In order to improve the solubility and absorption of sorafenib, microprecipitated bulk powder (MBP) formulations were prepared with Eudragit.
Methods: Eudragit E PO and Eudragit S100 were selected to prepare MBPs, which were fabricated by pH-controlled precipitation method. Drug-polymer mixture dissolved in dimethylacetamide was precipitated with an aqueous antisolvent, followed by freeze-drying. Physical properties including drug content, X-ray diffraction pattern and morphological properties were measured. In vitro drug dissolution was determined and in vivo pharmacokinetics was studied after oral administration of each MBP suspension in rats. Plasma concentration of sorafenib was analyzed by HPLC-MS/MS.
Results: X-ray diffraction study showed that sorafenib was encapsulated in Eudragit as an amorphous form. Nano-sized particles were observed by scanning electron microscopy. Eudragit E PO-MBP enhanced dissolution of sorafenib in acidic conditions, while Eudragit S100-MBP in higher pH condition. In pharmacokinetic study, MBPs significantly increased the AUC of sorafenib than its powder form. Moreover, Eudragit S100-MBP showed higher AUC than Eudragit E PO-MBP.
Conclusion: MBP formulation can increase the dissolution of sorafenib, thereby enhancing its oral bioavailability in rats.
Ju-Hwan Park– Post-doc, Seoul National University, Seoul-t'ukpyolsi