Evaluation of polymer carriers with regard to the bioavailability enhancement of bifendate solid dispersions prepared by hot-melt extrusion

Abstract

Objective: The aim of this study was to evaluate several polymer carriers with regard to the bioavailability enhancement of bifendate solid dispersions (SD) prepared by hot-melt extrusion (HME) and select the most appropriate polymer carrier.

Methods: Solid dispersions containing bifendate in different polymers, including Plasdone^® S-630, Eudragit^® EPO and Kollidon^® VA 64 were prepared by hot-melt extrusion. Differential scanning calorimetry (DSC), Powder X-ray diffraction (XRD) and dissolution testing were used to characterize the systems. Then, the thermal degradation during the HME process and the storage stability of tablets consisting of bifendate-Kollidon^® VA 64 SD were investigated. Finally, the oral bioavailability of bifendate dosage forms with bifendate-Plasdone^® S-630 (1/9), bifendate-Eudragit^® EPO (1/4) and bifendate-Kollidon^® VA 64 (1/9) SD in beagle dogs was compared with that of commercially available benfidate pills.

Results: DSC and XDR analysis showed the dispersion of the drug in the polymer on a molecular basis or in the amorphous state. The drug release from both bifendate-Plasdone^® S-630 SD and bifendate-Eudragit^® EPO SD was up to more than 90% with the pH 1.2 simulated gastric fluid as the dissolution medium, while the relative bioavailability was just 87.8 ± 51.8% and 110 ± 62% compared with commercial pills, respectively. The directly compressed tablets with bifendate-Kollidon^® VA 64 SD were found to dissolve rapidly over 95% within 30 min and the relative bioavailability was 145.0 ± 35.2%.

Conclusion: The bioavailability of water-insoluble bifendate was markedly enhanced by dispersing the drug in the polymer carrier Kollidon^® VA 64 employing HME technology.

Keywords::

• Bifendate
• polymer carriers
• hot-melt extrusion
• characterization
• related substance
• bioavailability

Acknowledgments

We wish to thank Zhang Ling and Li Hui for their technical assistant.

Declaration of interest

The authors report no conflicts of interest.