Study of Orally Disintegrating Tablets Using Erythritol as an Excipient Produced by Moisture-Activated Dry Granulation (MADG)

Mizuki Yamada, Agata Ishikawa, Shun Muramatsu, Takayuki Furuishi, Yoshinori Onuki, Kaori Fukuzawa, Etsuo Yonemochi

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Moisture-activated dry granulation (MADG) is an eco-friendly granulation method that uses a small amount of water and insoluble excipients to absorb moisture. MADG is expected to improve productivity and reduce costs. Erythritol, an excipient used for preparing orally disintegrating tablets (ODTs), has poor tabletability and is difficult to form into tablets by conventional methods, such as high-shear granulation (HSG) and direct compression. In this study, we optimized the manufacturing conditions for ODTs to improve the tabletability of erythritol using MADG. The disintegration time of tablets made using the MADG method was approximately one-tenth that of those made using the HSG method, and the hardness was approximately 1.4 times higher. Moreover, MADG could delay disintegration and improve tabletability. We further attempted to optimize the manufacturing conditions using MADG, particularly in terms of the amount of water used. The disintegration time increased as the amount of added water increased. Moreover, water absorption tests revealed that capillary wetting decreased as the amount of water added increased, but the initial wetting did not change. These results suggested that the disintegration time was prolonged because of the increase in granule density and decrease in capillary wetting with the increase in the amount of added water. The hardness of the tablets increased because of the easy deformation of the granules after the addition of up to 3% water; however, when more than 3% water was added, the hardness decreased because of the aggregation of the granules with the excess water. Finally, two-dimensional maps of the effect of the amount of added water and water activity indicated that tablets with a hardness of ≥80 N and a disintegration time of ≤15 s could be produced by adjusting the amount of added water to within the range of 2.2–3.3% and water activity to 0.3–0.53. These results indicate that MADG can improve the tabletability of erythritol and be used for the granulation of ODTs. Tablets with appropriate hardness and disintegration properties can be produced by adjusting the water content to approximately 2.7% and the water activity to approximately 0.4 when producing ODTs with MADG.

Original languageEnglish
Article number1004
Issue number8
Publication statusPublished - 2022 Aug
Externally publishedYes


  • disintegration
  • erythritol
  • moisture-activated dry granulation
  • orally disintegrating tablet
  • water activity

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery


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