Preparation of cefuroxime axetil nanoparticles by rapid expansion of supercritical fluid technology

Abstract

As a poorly water-soluble drug, cefuroxime axetil (CFA) features a low solubility and dissolution rate in the gastrointestinal tract, which limits its effective absorption and bioavailability. The objective of this study was production of amorphous CFA nanoparticles directly without any additive by rapid expansion of supercritical solution technology. The effects of process parameters, such as the temperature of nozzle (50–70 °C) and extraction port (60–90 °C) were investigated each in three levels, on the properties of the formed particles by a full factorial design. The particles were then analyzed for differential scanning calorimetry (DSC), X-ray diffraction (XRD), particle size, zeta potential and dissolution properties. Z-average particle size of different nanoparticles was between 158 and 513 nm and zeta potential also changed from − 4.29 to − 42.8 mV. The lowest particle size was seen in sample with nozzle temperature at 60 °C and the extraction temperature at 90 °C. However, when temperatures of nozzle and extraction column were decreased to 50 °C and 75 °C respectively, the particle size was increased to 465 nm. More than 90% of the some nano-sized CFA formulations were dissolved in 3 min and complete dissolution occurred within 20 min, while the commercial CFA did not achieve complete dissolution (only about 50%) during 60 min of the testing period.