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Development of a patient-centric formulation of tegoprazan, a novel potassium-competitive acid blocker, using modified-release drug-coated pellets

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Abstract

Purpose

The purpose of this study was to develop a patient-centric formulation of tegoprazan, a novel potassium-competitive acid blocker, using modified-release drug-coated pellets.

Methods

Tegoprazan tablets, sustained-release (SR) polymer-coated pellets, SR drug-coated pellets, enteric-coated (DR) pellets, SR polymer-coated pellets with an enteric coating (CR1), SR drug-coated pellets with an enteric coating (CR2), and tegoprazan immediate-release (IR) powder were prepared. Dual-release capsules were prepared by combining the IR powder with the CR1, CR2, and DR pellets (IR/CR1, IR/CR2, and IR/DR, respectively). In vitro dissolution tests were conducted to screen the formulations, and in vivo pharmacokinetic (PK) analysis was conducted using cynomolgus monkeys. Design of experiments was employed to optimize the formulation for the CR2 pellets. The effect of the particle size on the dissolution profile of the CR2 pellets was investigated using scanning electron microscopy.

Results

In vitro dissolution of the IR/CR1 capsule produced the desired pH- and time-dependent release profile, and in vivo PK analysis confirmed that drug absorption was well-controlled by this formulation. The IR/CR2 capsule exhibited a pH- and time-dependent release of tegoprazan that was similar to that of the IR/CR1 capsule. Small drug particles appeared to become embedded in the densely packed coating, thus dissolving more slowly than the medium and large drug particles.

Conclusion

Unlike the CR1 pellets, the CR2 pellets did not require an additional coating and curing process. The developed IR/CR2 capsule is also expected to prevent nocturnal acid breakthrough and thus improve patient compliance.

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Acknowledgements

This research was supported by HK inno.N Corp. and by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. NRF- 2020M3E5D9080795). The authors thank all researchers involved in the tegoprazan program at HK inno.N Corp.

Conflict of interest

All authors (S.C. Lee, M. Kim, D. Kim, E.K. Jeon, and E.H. Lee) declare that they have no conflicts of interest.

Statement of human and animal rights

All experimental procedures regarding the evaluation of pharmacokinetic characteristics in non-clinical models were performed following the regulations of the Animal Experimental Ethics Committee (IACUC, Institutional Animal Care and Use Committee, Approval No. ORIENT-IACUC-20124).

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Authors and Affiliations

  1. Novel Drug Research Center, HK inno.N Corp., 811, Deokpyeong-ro, Majang-myeon, Icheon-si, Gyeonggi-do, Korea

    Su Chul Lee, Myeongjoong Kim, Donghyun Kim & Eun Kyung Jeon

  2. College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong, 30019, Korea

    Su Chul Lee & Eun Hee Lee

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  1. Su Chul Lee
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  2. Myeongjoong Kim
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  3. Donghyun Kim
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Correspondence to Eun Hee Lee.

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Lee, S.C., Kim, M., Kim, D. et al. Development of a patient-centric formulation of tegoprazan, a novel potassium-competitive acid blocker, using modified-release drug-coated pellets. J. Pharm. Investig. 52, 623–638 (2022). https://doi.org/10.1007/s40005-022-00582-y

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