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Efficient Evaluation of In Vivo Performance in Human for Generic Formulation by Novel Dissolution-Absorption Prediction (DAP) Workflow

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Abstract

Purpose

The pharmaceutical bioequivalence of generic medicines must be confirmed with corresponding original drugs. Although the in vitro dissolution tests are required, results of the mandatory in vitro study do not necessarily reflect the in vivo performance after oral administration. Then, we have tried to develop the novel “Dissolution-Absorption Prediction (DAP) workflow” to evaluate the in vivo performance of generic medicines.

Methods

The DAP workflow consists of an “In vitro two-cell connected dissolution (TCCD) system” mimicking the changes in the luminal pH associated with gastrointestinal transit of medicines, “Evaluation of pharmacokinetics of active pharmaceutical ingredient (API)” and “Prediction of plasma concentration–time profile”. TCCD system-evaluated dissolution kinetics of APIs from generic formulations and pharmacokinetic parameters based on human data regarding the original drugs were used to calculate the plasma concentration–time profiles of APIs after the oral administration of generic medicines.

Results

The mandatory in vitro dissolution tests indicated that the dissolution properties of valsartan (BCS class II) and fexofenadine (BCS class III/IV) in generic formulations did not coincide with those in the corresponding original formulations. The TCCD system provided the very similar dissolution kinetics for the generic and original formulations for the two APIs. Plasma concentration–time profiles evaluated utilizing the dissolution profiles obtained by the TCCD system were in good agreement with the observed profiles for both the generic and original formulations for each API.

Conclusions

The DAP workflow would be valuable for estimating the in vivo performance of generic formulation and deducing their bioequivalence with the original formulation.

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Acknowledgments

This study was performed as the joint research between Towa Pharmaceutical Co., Ltd. and Okayama University.

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Authors and Affiliations

  1. Medical Analysis Research Department, Pharmaceutical Research & Technology Division, Towa Pharmaceutical Co., Ltd, Kyoto Research Park KISTIC #202, 134, Chudoji Minami-machi, Shimogyo-ku, Kyoto, Japan

    Motoki Onishi, Maiko Jiko, Kayo Koike, Hidetoshi Hashizume & Kazuhide Imagaki

  2. Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama, 700-8530, Japan

    Motoki Onishi, Masato Maruyama & Kazutaka Higaki

  3. Department of Bio-Technology, Osaka Bio-Medical College, 1-14-30 Shimanouchi, Chuo-ku, Osaka, Japan

    Kozo Tagawa

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  1. Motoki Onishi
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  4. Kayo Koike
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  6. Hidetoshi Hashizume
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  7. Kazuhide Imagaki
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  8. Kazutaka Higaki
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Contributions

Motoki Onishi; Conceptualization, Methodology, Writing, Acquisition, Analysis and interpretation of data: Kozo Tagawa; Conceptualization, Methodology: Maiko Jiko; Acquisition of data: Kayo Koike; Acquisition of data: Masato Maruyama; Interpretation of data: Hidetoshi Hashizume; Interpretation of data: Kazuhide Imagaki; Supervision: Kazutaka Higaki; Conceptualization, Methodology, Writing, Visualization, interpretation of data, Supervision.

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Correspondence to Kazutaka Higaki.

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Onishi, M., Tagawa, K., Jiko, M. et al. Efficient Evaluation of In Vivo Performance in Human for Generic Formulation by Novel Dissolution-Absorption Prediction (DAP) Workflow. Pharm Res 39, 2203–2216 (2022). https://doi.org/10.1007/s11095-022-03337-4

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