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Design of experiment (DoE)-based formulation design of bepotastine sustained-release tablet and in vitro-in vivo pharmacokinetic correlation

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Abstract

Purpose

Bepotastine besilate, a second-generation antihistamine commonly prescribed to treat allergic rhinitis and urticarial/pruritus, has a short half-life (t1/2) and is currently available as an immediate-release tablet, administered twice daily. The development of a sustained-release bepotastine formulation remains limited.

Methods

An experimental method was used to develop a sustained-release bepotastine tablet that can be taken once daily. The formulated sustained-release bepotastine tablet was biologically equivalent to the commercially available Talion® taken twice daily. Considering the target formulation characteristics, the in vitro dissolution rates at 1, 3, and 10 h were predicted as critical quality attributes, taking into account the dissolution and bioequivalence profile of Talion®.

Results

Factors capable of critically impacting the sustained-release pattern were selected by performing a screening study; the X value, which affects the Y value (1, 3, and 10 h dissolution rates), was identified using hydroxypropyl methylcellulose, polyvinyl-alcohol, and citric acid. For the three identified independent variables, a design space was derived using the extreme vertices design from among the experimental design mixture methods, optimized within the X values of the derived design space. The optimized formulation employed a direct compression process to minimize time and cost. The dissolution rates at 1, 3, and 10 h were 24.9, 47.4, and 88.8%, respectively, exhibiting an appropriate dissolution profile to induce sustained-release effects in the human body.

Conclusion

Bepotastine sustained-release tablet, which can be administered once daily, developed by applying the design of experiment method, was biologically equivalent to the Talion® tablet, which is administered twice daily. Therefore, the developed sustained-release technology using two or more hydrophilic polymers can be applied to various pharmaceuticals in the future as a platform to overcome the technical and commercial limitations of sustained-release agents.

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Authors and Affiliations

  1. IMDpharm Inc, 17, Daehak 4-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, Republic of Korea

    Sang-Won Jeon & Young-Joon Park

  2. Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, 77 jeongneung-ro, Sseongbuk-gu, Seoul, 02707, Republic of Korea

    Joo-Eun Kim

  3. College of Pharmacy, Ajou University, 206, World Cup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do, Republic of Korea

    Sang-Won Jeon, Jin-Hyun Park & Young-Joon Park

Authors
  1. Sang-Won Jeon
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  2. Jin-Hyun Park
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  3. Joo-Eun Kim
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Corresponding authors

Correspondence to Joo-Eun Kim or Young-Joon Park.

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Conflict of interest

All authors (S.W. Jeon, J.H. Park, J.E. Kim, and Y.J. Park) declare that they have no conflict of interest.

Research involving human or animal participants

All animal testing procedures complied with the Animal Welfare Act and the guidelines for the protection and use of experimental animals and were approved by the Animal Management and Use Committee of KPC, Korea (IRB No. P192021; Identification code: E2016063; Approval date: March 01, 2016).

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Jeon, SW., Park, JH., Kim, JE. et al. Design of experiment (DoE)-based formulation design of bepotastine sustained-release tablet and in vitro-in vivo pharmacokinetic correlation. J. Pharm. Investig. 53, 407–416 (2023). https://doi.org/10.1007/s40005-023-00611-4

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  • DOI: https://doi.org/10.1007/s40005-023-00611-4

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