Granulated Ammonium Alginate as a Functional Sodium-Sequestration Agent: Formulation Optimization Using Box–Behnken Design
Abstract
Excessive salt intake is a major risk factor for cardiovascular, cerebrovascular, and renal diseases, highlighting the need for strategies to reduce intestinal sodium absorption. Ammonium alginate (AAL) suppresses the postprandial increase in blood sodium levels and promotes fecal sodium excretion via ion-exchange and gel-mediated sodium entrapment in the gastrointestinal tract. However, its unpleasant odor and taste, along with its high viscosity upon contact with saliva, cause oral discomfort and limit its practical use in food and clinical settings. In this study, AAL granules were developed to improve their handling and sensory properties while preserving their sodium-sequestration functionality. Granulation with the AQshelax coating was performed using a fluidized-bed granulator, and the process parameters were optimized using a Box-Behnken experimental design. The optimized granules exhibited improved flowability and markedly reduced viscosity upon contact with saliva, resulting in enhanced sensory evaluation scores. In vitro sodium-binding assays demonstrated that the optimized granules retained a sodium-binding capacity comparable to that of unprocessed AAL powder. Furthermore, in salt-loaded mice, granulated AAL maintained its ability to suppress elevated blood sodium levels in vivo. These findings indicate that design-of-experiments-guided granulation successfully overcame key formulation limitations without compromising sodium-sequestration functionality, thereby enabling the practical dietary and clinical application of AAL as a sodium-excreting agent.
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BibTeX
@article{shimada2026granulated,
title = {{Granulated Ammonium Alginate as a Functional Sodium-Sequestration Agent: Formulation Optimization Using Box–Behnken Design}},
author = {Gosuke Shimada and Yuto Higa and Kazuki Shimogoryou and Maria Yamaguchi and Toru Taharabaru and Yuya Hayashi and Hidenori Takeshita and Taishi Higashi and Keiichi Motoyama},
journal = {Chemical and Pharmaceutical Bulletin},
year = {2026},
month = sep,
doi = {10.1248/cpb.c26-00322},
url = {https://www.jstage.jst.go.jp/article/cpb/74/9/74_c26-00322/_article},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Granulated Ammonium Alginate as a Functional Sodium-Sequestration Agent: Formulation Optimization Using Box–Behnken Design
AU - Gosuke Shimada
AU - Yuto Higa
AU - Kazuki Shimogoryou
AU - Maria Yamaguchi
AU - Toru Taharabaru
AU - Yuya Hayashi
AU - Hidenori Takeshita
AU - Taishi Higashi
AU - Keiichi Motoyama
PY - 2026
DA - 2026/09/15
JO - Chemical and Pharmaceutical Bulletin
DO - 10.1248/cpb.c26-00322
UR - https://www.jstage.jst.go.jp/article/cpb/74/9/74_c26-00322/_article
AB - Excessive salt intake is a major risk factor for cardiovascular, cerebrovascular, and renal diseases, highlighting the need for strategies to reduce intestinal sodium absorption. Ammonium alginate (AAL) suppresses the postprandial increase in blood sodium levels and promotes fecal sodium excretion via ion-exchange and gel-mediated sodium entrapment in the gastrointestinal tract. However, its unpleasant odor and taste, along with its high viscosity upon contact with saliva, cause oral discomfort and limit its practical use in food and clinical settings. In this study, AAL granules were developed to improve their handling and sensory properties while preserving their sodium-sequestration functionality. Granulation with the AQshelax coating was performed using a fluidized-bed granulator, and the process parameters were optimized using a Box-Behnken experimental design. The optimized granules exhibited improved flowability and markedly reduced viscosity upon contact with saliva, resulting in enhanced sensory evaluation scores. In vitro sodium-binding assays demonstrated that the optimized granules retained a sodium-binding capacity comparable to that of unprocessed AAL powder. Furthermore, in salt-loaded mice, granulated AAL maintained its ability to suppress elevated blood sodium levels in vivo. These findings indicate that design-of-experiments-guided granulation successfully overcame key formulation limitations without compromising sodium-sequestration functionality, thereby enabling the practical dietary and clinical application of AAL as a sodium-excreting agent.
SN - 1347-5223
SN - 0009-2363
ER -