monooctanoin and tocophersolan

Lipid based drug delivery systems have gained prominence in last decade for drugs with dissolution rate limited oral bioavailability.. 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.. 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.. 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.. SNEDDS formulations led to improved oral bioavailability due to enhanced solubilization of selected drug.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Area Under Curve; Biological Availability; Caprylates; Cefpodoxime Proxetil; Ceftizoxime; Drug Delivery Systems; Drug Stability; Emulsions; Female; Glycerides; Humans; Male; Nanoparticles; Polyethylene Glycols; Polysorbates; Rats; Rats, Wistar; Succinates; Vitamin E

The accelerating effect of polyethylene glycol 400 on small intestinal transit has been previously reported. The aim of this study was to investigate the influence of other solubility-enhancing excipient, propylene glycol, D-alpha-tocopheryl-polyethylene glycol-1,000 succinate (VitE-TPGS) and Capmul MCM, on human intestinal transit. A 5-g dose of each excipient was administered to seven healthy male subjects. Propylene glycol and VitE-TPGS were administered dissolved in 150 mL water. Capmul MCM was administered in the form of four 000 hard gelatin capsules to mask its taste and then given with 150 mL water. On a separate occasion, 150 mL water was administered as the control. Each formulation was radiolabelled with technetium-99 m to follow its transit using a gamma camera. The mean small intestinal transit times were 234, 207, 241 and 209 min for the control, propylene glycol, VitE-TPGS and Capmul MCM treatments, respectively. Although there were differences in the small intestinal transit times for the excipients investigated compared with the control, none of the results were statistically significant. Unlike polyethylene glycol 400 at the same dose of 5 g, the excipients tested (propylene glycol, VitE-TPGS and Capmul MCM) had little or no impact on small intestinal transit.

Topics: Adult; Caprylates; Chemistry, Pharmaceutical; Excipients; Gastric Emptying; Gastrointestinal Transit; Glycerides; Humans; Male; Middle Aged; Polyethylene Glycols; Propylene Glycol; Vitamin E