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Context: Lipid based drug delivery systems have gained prominence in last decade for drugs with dissolution rate limited oral bioavailability. Objective: To improve the solubility, permeability and oral bioavailability of cefpodoxime proxetil, β-lactam antibiotic. It is BCS Class IV drug having solubility 400 µg/mL and 50% oral bioavailability. Materials and methods: Self-nanoemulsifying drug delivery system (SNEDDS) using various surfactant and cosurfactants such as tween 80, tocopheryl polyethylene glycol succinate (TPGS), propylene glycol and Capmul MCM as oil phase were prepared. Ternary phase diagrams were constructed to identify stable microemulsion region. Percent transmittance studies helped to shortlist the surfactant-cosurfactant combination. Results and discussion: Tween 80 and TPGS as surfactants and Capmul MCM as oil phase were found to produce stable nanoemulsions. Five formulations of SNEDDS had globule size of 55-60 nm and zeta potential of -4 to -11 mV. Self-emulsification time was between 221 and 370 s, while viscosity was dependent on composition of SNEDDS. Cloud point was above 70°C which indicated the retention of in vivo self-emulsifying properties. Average flux for cefpodoxime proxetil (CP) and SNEDDS was 0.104 and 0.985 µg/cm(2) min. Permeability was 19.72 and 206 for CP and SNEDDS. Liquid SNEDDS spray coated onto micropellets of microcrystalline cellulose (18-20#) were analysed by scanning electron microscope (SEM), self-emulsification and in vitro dissolution. A 5.36-fold increase in area under curve AUC(0-∞) was observed for CP-SNEDDS than plain drug. Minimum inhibitory concentration (MIC) was lower for SNEDDS. Liquid and SNEDDS micropellets were stable under accelerated conditions. Conclusion: SNEDDS formulations led to improved oral bioavailability due to enhanced solubilization of selected drug.
Department of Pharmaceutics, SVKM'S B.N. College of Pharmacy , Mumbai , India.
This article was published in the following journal.
Name: Drug development and industrial pharmacy
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