ADMET and DMPK (Aug 2019)

Harmonizing solubility measurement to lower inter-laboratory variance – progress of consortium of biopharmaceutical tools (CoBiTo) in Japan

  • Asami Ono,
  • Naoya Matsumura,
  • Takahiro Kimoto,
  • Yoshiyuki Akiyama,
  • Satoko Funaki,
  • Naomi Tamura,
  • Shun Hayashi,
  • Yukiko Kojima,
  • Masahiro Fushimi,
  • Hiroshi Sudaki,
  • Risa Aihara,
  • Yuka Haruna,
  • Maiko Jiko,
  • Masaru Iwasaki,
  • Takuya Fujita,
  • Kiyohiko Sugano

DOI
https://doi.org/10.5599/admet.704
Journal volume & issue
Vol. 7, no. 3
pp. 183 – 195

Abstract

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The purpose of the present study was to harmonize the protocol of equilibrium solubility measurements for poorly water-soluble drugs to lower inter-laboratory variance. The “mandatory” and “recommended” procedures for the shake-flask method were harmonized based on the knowledge and experiences of each company and information from the literature. The solubility of model drugs was measured by the harmonized protocol (HP) and the non-harmonized proprietary protocol of each company (nonHP). Albendazole, griseofulvin, dipyridamole, and glibenclamide were used as model drugs. When using the nonHP, the solubility values showed large inter-laboratory variance. In contrast, inter-laboratory variance was markedly reduced when using the HP.

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