Improved Oral Bioavailability of Cefuroxime Axetil Utilizing Nanosuspensions Developed by Media Milling Technique

Cefuroxime axetil is a Class IV drug as per the Biopharmaceutical Classification System. It is a prodrug of Cefuroxime which is practically insoluble in water with a log P of 3.8. The absolute bioavailability of cefuroxime axetil, determined after intravenous injection of 1 g of cefuroxime and oral administration of 1 g of cefuroxime axetil (uncoated tablet), is 32-35% (range 23-44%). The present investigation was aimed at preparation of nanosuspension of Cefuroxime axetil for improving its solubility and thereby its bioavailability. Cefuroxime axetil nanosuspensions were prepared by the media milling technique using zirconium oxide beads and characterized by particle size, saturation solubility, differential scanning calorimetry, scanning electron microscopy and transmission electron microscopy. The nanosuspensions were evaluated for in vivo diffusion studies, ex vivo intestinal permeability studies and in vivo bioavailability studies. The particle size of the drug was drastically reduced to 221.2±0.26 nm from 5 μm after nanosizing. Saturation solubility achieved was 2387±3.35 μg/ml which was 16 times more than the bulk drug. DSC thermograms confirmed the non interference of excipients on the drug particles. In vivo diffusion studies showed 94.17±5.689% drug release from nanosuspension as against 62.34±1.139% release from plain Cefuroxime axetil suspension in 24 hours. Similarly, for ex vivo studies, 57.52±1.159% was released from plain Cefuroxime Axetil suspension in comparison to 85.58±3.12% for nanosuspension in 24 hours. In vivo studies in rats demonstrated a two times increase in oral bioavailability from the nanosuspension in comparison to marketed formulation. Therefore, nanosuspension which exhibited improved solubility, dissolution and absorption could be a better option as a delivery system compared to the present oral suspension formulation.