Cefdinir nanosuspension for improved oral bioavailability by media milling technique: formulation, characterization and in vitro–in vivo evaluations

Abstract

Cefdinir (Cef) is an orally active Biopharmaceutics Classification System (BCS) class IV drug with incomplete absorption and low bioavailability (16–21%). The aim of this investigation was to develop nanosuspensions (NS) of Cef to improve its oral bioavailability. Cef NS were prepared by the media milling technique using zirconium oxide beads as the milling media. Cef NS were characterized by particle size, Scanning Electron Microscopy, Differential Scanning Calorimetry, X-Ray Diffraction pattern and evaluated for saturation solubility, in vitro release studies, ex vivo permeability studies and in vivo bioavailability studies. The particle size and zeta potential were found to be 224.2 ± 2.7 nm and −15.7 ± 1.9 mV, respectively. Saturation solubility of NS was found to be 1985.3 ± 10.2 µg/ml which was 5.64 times higher than pure drug (352.2 ± 6.5 µg/ml). The DSC thermograms and XRD patterns indicated that there was no interaction between drug and excipients and that the crystallinity of Cef remained unchanged after media milling process. Results of in vitro release studies and ex vivo permeation studies showed improved drug release of 88.2 1 ± 2.90 and 83.11 ± 2.14%, respectively, from NS after 24 h as compared to drug release of 54.09 ± 2.54 and 48.2 1 ± 1.27%, respectively, from the marketed suspension (Adcef). In vivo studies in rats demonstrated a 3-fold increase in oral bioavailability from the NS in comparison to marketed suspension. The results of this investigation conclusively show that the developed nanosuspension of Cef exhibited improved solubility, dissolution and permeation which led to a significant enhancement in its oral bioavailability.

• Dissolution velocity
• lyophilization
• Noyes–Whitney equation
• poorly water soluble drugs
• saturation solubility

Acknowledgements

The authors would like to thank Torrent Research Centre, India, for providing Cefdinir as a gift sample, and Sun Pharmaceutical Industries Ltd., India, for the gift sample of zirconium oxide beads. The authors are grateful to the Metallurgy Department, The Maharaja Sayajirao University of Baroda, Vadodara, India, for XRD and SEM studies and to the Pharmacology Department, Pharmacy Department for their help in the in vivo studies.

Declaration of interest

The authors report no conflict of interest.