Comparative study of binary and ternary axitinib solid dispersions: in vitro physicochemical characterization and in vivo pharmacokinetics

The efficacy of axitinib (Axi) for treating various cancers has been demonstrated clinically. However, the poor aqueous solubility of Axi limits its application. In this study, the solubility enhancement and recrystallization inhibition effect of different cellulose derivatives and surfactants were evaluated systematically. Ternary amorphous solid dispersions of Axi (Axi TSDs) were prepared with hypromellose succinate HF (HPMCAS HF) as a recrystallization inhibitor and polyoxyethylene hydrogenated castor oil as the wetting agent. Binary amorphous solid dispersions of Axi (Axi BSDs) were also prepared with mere HPMCAS HF for further comparative study. Distinct liquid−liquid phase separation state of Axi was revealed in the binary and ternary system. Differential scanning calorimetry and powder X-ray diffraction assays confirmed that the crystalline state of Axi had successfully transformed to an amorphous state in both Axi BSDs and Axi TSDs, with morphological validation provided by scanning electron microscopy. Energy dispersive spectrometer and Fourier transform infrared spectroscopy demonstrated homogeneous excipient distribution around Axi, mediated through physical molecular interaction. Axi TSDs exhibited superior dissolution profiles in different pH media and simulated gastrointestinal fluid compared to Axi BSDs and Axi bulk powder. Pharmacokinetic evaluation in rats of Axi TSDs revealed significantly enhanced bioavailability, with an area under the plasma concentration-time curve value 2.1 times higher than Axi bulk powder and 1.5 times higher than Axi BSDs. These findings established the ternary amorphous system as a robust platform for enhancing the biopharmaceutical performance of hydrophobic therapeutics.