Development of selumetinib-loaded solid dispersion based on low molecular weight methylcellulose for the enhanced...

The poor water solubility and bioavailability of selumetinib sulfate (SEL) limit its clinical potential as a promising anticancer drug. The aim of this study was to develop a solid dispersion (SD) of SEL as a new formulation strategy. Methylcellulose 4 cP (MC 4 cP) and Soluplus® were selected as SD carriers for their high solubility of SEL (>1400 μg/mL at pH 1.2). Furthermore, the low molecular weight MC 4 cP was effective in the solubilization of SEL due to its specific molecular affinity and interaction with SEL. The SDs of SEL/MC 4 cP and SEL/Soluplus® were prepared using the spray drying method. All the SDs demonstrated the transformation of crystalline SEL into amorphous form with particle size of <20 μm, in scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry. The optimized F3 (SEL/MC 4 cP = 1/10, w/w) exhibited more than twice the dissolution rate of SEL (100.15 ± 1.81 %) at pH 1.2 and 60 min compared with the raw SEL (45.13 ± 2.13 %) and F4 (SEL/Soluplus® = 1/5, w/w) (42.44 ± 1.43 %). F3 showed stable amorphous form without any recrystallization of SEL for 6 months at 40 °C. Furthermore, F3 enhanced oral absorption (1.96-fold in C_max and 1.69-fold in AUC_inf) in rats compared with the raw SEL suspension group, and this improvement was further supported by its nearly 100 % absolute bioavailability. In conclusion, F3 suggested in this work was a potential novel SD formulation for SEL, offering enhanced solubility, dissolution, physical stability, and bioavailability.