A cochleate formulation optimized by D-optimal mixture design enhances oral bioavailability of Revaprazan

Abstract

A cochleate formulation was developed to enhance the oral bioavailability of revaprazan (RVP). Dimyristoyl phosphatidylcholine (DMPC) liposome containing dicetyl phosphate (DCP) successfully formed a cochleate after treatment with CaCl₂, whereas that containing sodium deoxycholate did not. Cochleate was optimised using a D-optimal mixture design with three independent variables—DMPC (X₁, 70.58 mol%), cholesterol (X₂, 22.54 mol%), and DCP (X₃, 6.88 mol%)—and three response variables: encapsulation efficiency (Y_1, 76.92%), released amount of free fatty acid at 2 h (Y₂, 39.82%), and released amount of RVP at 6 h (Y₃, 73.72%). The desirability function was 0.616, showing an excellent agreement between the predicted and experimental values. The cylindrical morphology of the optimised cochleate was visualised, and laurdan spectroscopy confirmed the dehydrated membrane interface, showing an increased generalised polarisation value (approximately 0.5) over small unilamellar vesicle of RVP (RVP-SUV; approximately 0.1). The optimised cochleate showed greater resistance to pancreatic enzyme than RVP-SUV. RVP was released in a controlled manner, achieving approximately 94% release in 12 h. Following oral administration in rats, the optimised cochleate improved the relative bioavailability of RVP by approximately 274%, 255%, and 172% compared to RVP suspension, a physical mixture of RVP and the cochleate, and RVP-SUV, respectively. Thus, the optimised cochleate formulation might be a good candidate for the practical development of RVP.

Keywords:

• Revaprazan
• cochleate
• D-optimal mixture design
• laurdan spectroscopy
• enzyme stability
• oral bioavailability

Acknowledgements

The authors thank to ESSAYREVIEW (www.essayreview.co.kr) for English language editing (#139072).

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) [No. 2022R1A2B5B02001794]. This work was also supported by the Brain Korea (BK) 21 FOUR through the NRF funded by the Ministry of Education of Korea.