Preparation and in vitro/in vivo evaluation of azilsartan osmotic pump tablets based on the preformulation investigation

Abstract

The objective of this study was to design and evaluate azilsartan osmotic pump tablets. Preformulation properties of azilsartan were investigated for formulation design. Azilsartan osmotic pump tablets were prepared by incorporation of drug in the core and subsequent coating with cellulose acetate and polyethylene glycol 4000 as semi-permeable membrane, then drilled an orifice at the center of one side. The influence of different cores, compositions of semipermeable membrane and orifice diameter on azilsartan release were evaluated. The formulation of core tablet was optimized by orthogonal design and the release profiles of various formulations were evaluated by similarity factor (f₂). The optimal formulation achieved to deliver azilsartan at an approximate zero-order up to 14 h. The pharmacokinetic study was performed in beagle dogs. The azilsartan osmotic pump tablets exhibited less fluctuation in blood concentration and higher bioavailability compared to immediate-release tablets. Moreover, there was a good correlation between the in vitro dissolution and in vivo absorption of the tablets. In summary, azilsartan osmotic pump tablets presented controlled release in vitro, high bioavailability in vivo and a good in vitro-in vivo correlation.

Keywords:

• Azilsartan
• preformulation properties
• osmotic pump tablets
• orthogonal design
• in vitro release
• pharmacokinetics

Compliance with ethical standards

Animal experiments were carried out following protocols approved by the animal ethics committee of Anhui University of Chinese Medicine.

Acknowledgements

The authors are grateful to Ping Ma professor for English writing polishing.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The work was financially supported by Science and Technology breakthrough project of Anhui provincial science and technology department, Anhui province in China under Grant: 1301042097.