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Development of Sustained Release System Based on High Water-Absorbable Gel Formation Using Croscarmellose Sodium, Alkaline Excipients and HPMC (ACSH SR System); Novel Application of Croscarmellose Sodium as a Gel Former

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Abstract

Purpose

Croscarmellose sodium, generally used as a superdisintegrant in pharmaceutical formulations, is hydrolyzed to form the gel structure under basic pH conditions. Utilizing this property of croscarmellose sodium, we developed a novel sustained release (SR) system.

Methods

Immediate release (IR) and SR tablets containing croscarmellose sodium, alkaline excipients and/or hydroxypropyl methylcellulose (HPMC) were prepared and examined for wet strength and in vitro drug release behavior. In vivo oral drug absorption was evaluated for IR tablets, HPMC tablets and our novel SR tablets in fasted Beagle dogs.

Results

To form the gel structure even under the physiological condition, alkaline excipients were added into the formulation containing croscarmellose sodium. Furthermore, HPMC was used to make the gel structure strong enough against mechanical destructive forces. The novel alkalized croscarmellose sodium-HPMC (ACSH) SR tablet, consisting of croscarmellose sodium, alkaline excipients, and HPMC, successfully sustained the release of acetaminophen, ibuprofen, or nicardipine hydrochloride, compared with the IR tablets. The ACSH SR system provided a better release of acetaminophen than the HPMC tablet without croscarmellose sodium in the release study using a small volume of liquid, suggesting that substantial release and subsequent absorption would be expected in the distal intestinal segments after oral dosing. The in vivo oral absorption study revealed that the ACSH SR system successfully suppressed and prolonged the plasma concentrations of acetaminophen.

Conclusion

This novel ACSH SR system prepared with croscarmellose sodium, alkaline excipients, and HPMC, would be a promising SR formulation for enabling substantial drug absorption in the distal intestinal segments.

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Data Availability

Data will be made available on request.

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Funding

This research did not receive any specific grants from funding agencies in the public, commercial, or non-profit sectors.

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-Naka, Kita-Ku, Okayama, 700-8530, Japan

    Masato Gomi, Masato Maruyama & Kazutaka Higaki

  2. Formulation R&D Laboratory, Research Division, Shionogi & Co., Ltd., 2-1-3 Kuise Terajima, Amagasaki, Hyogo, 660-0813, Japan

    Masato Gomi, Naoya Mizutani, Ryotaro Senoo, Noriaki Matsubara & Go Kimura

  3. Laboratory for Medicinal Chemistry Research, Research Division, Shionogi & Co., Ltd., 3-1-1, Futaba-Cho, Toyonaka, Osaka, 561-0825, Japan

    Ayahisa Watanabe

Authors
  1. Masato Gomi
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  2. Naoya Mizutani
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  4. Noriaki Matsubara
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  8. Kazutaka Higaki
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Contributions

Masato Gomi; Conceptualization, Methodology, Writing, Visualization Acquisition, Analysis, and interpretation of data: Naoya Mizutani; Acquisition, Analysis, and interpretation of data: Ryoutarou Senoo; Acquisition of data: Noriaki Matsubara; Acquisition of data: Ayahisa Watanabe; Interpretation of data: Masato Maruyama; Interpretation of data: Go Kimura; Interpretation of data: Kazutaka Higaki; Conceptualization, Methodology, Writing, Visualization, interpretation of data, and Supervision.

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Correspondence to Masato Gomi.

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M. G., N. M., R. S., N. M., A. W., and G. K., are employees of Shionogi & Co., Ltd.

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Gomi, M., Mizutani, N., Senoo, R. et al. Development of Sustained Release System Based on High Water-Absorbable Gel Formation Using Croscarmellose Sodium, Alkaline Excipients and HPMC (ACSH SR System); Novel Application of Croscarmellose Sodium as a Gel Former. Pharm Res 40, 3073–3086 (2023). https://doi.org/10.1007/s11095-023-03630-w

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