Large-Scale Preparation of Amorphous Cefixime Nanoparticlesby Antisolvent Precipitation in a High-Gravity Rotating Packed Bed.

Toenhance the solubility and dissolution rate, and thus potentiallyimprove the oral bioavailability of cefixime (CFX), amorphous CFXnanoparticles were prepared via high-gravity antisolvent precipitation(HGAP) without the aid of any pharmaceutical additives in a rotatingpacked bed (RPB). The effects of operating variables on particle sizeand distribution were investigated. Compared to raw CFX, the meansize of prepared nanoparticles decreased greatly from about 2.1 μmto 57 nm, and the saturation solubility increased tremendously from0.289 to 0.951 mg/mL. CFX nanoparticles showed good stability andwere capable of generating a maximum supersaturation level, reachingup to ∼22.8 times of raw CFX’s saturation solubility.Further, CFX nanoparticles achieved 100% drug dissolution within 2min, while the raw drug did not dissolve completely after 45 min,suggesting that the solubility and dissolution properties of CFX nanoparticleswere significantly improved. Since the drug recovery ratio achieved99.9%, and the production capacity of lab-scale RPB with a continuousoperation reached 1.8 kg/h, the HGAP method might offer a generaland facile platform for mass production of CFX nanoparticles. [ABSTRACT FROM AUTHOR]