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<p>Tofacitinib (Tofa), a Biopharmaceutics Classification System Class III drug, exhibits pH-dependent solubility and a strong tendency to agglomerate, potentially affecting tablet uniformity, <i>in vitro</i> dissolution behavior, and <i>in vivo</i> performance. In this study, a Tofa free base tablet (WT2) prepared by wet granulation was evaluated in Beagle dogs and compared with a marketed reference tablet (RT). <i>In vitro</i> dissolution studies showed comparable drug release between WT2 and RT at pH 1.2 and 4.0, whereas WT2 exhibited slower, though still complete, dissolution at pH 6.8. Despite these differences, pharmacokinetic studies demonstrated comparable systemic exposure under both fasted and fed conditions. The geometric mean ratios and 90% confidence intervals for maximum plasma concentration (C<sub>max</sub>) and area under the plasma concentration–time curve from time zero to the last quantifiable concentration (AUC<sub>last</sub>) met conventional bioequivalence criteria. Food intake slightly delayed absorption but had no significant effect on the extent of exposure. This research shows that differences in dissolution arising from pH-dependent solubility did not meaningfully affect systemic exposure of Tofa free base under the studied conditions.</p> Graphical Abstract <p></p>

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Development and Evaluation of Tofacitinib Tablets with Comparative Dissolution and Pharmacokinetic Studies in Beagle Dogs

  • 期刊论文

  • 发表日期：

    2026年5月6日

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  • Deokkyu Lee,
  • Jain Koo,
  • Hyewon Jeon,
  • Jaehyun Cheong,
  • Dongmin Park,
  • Kyung Taek Oh

摘要

Tofacitinib (Tofa), a Biopharmaceutics Classification System Class III drug, exhibits pH-dependent solubility and a strong tendency to agglomerate, potentially affecting tablet uniformity, in vitro dissolution behavior, and in vivo performance. In this study, a Tofa free base tablet (WT2) prepared by wet granulation was evaluated in Beagle dogs and compared with a marketed reference tablet (RT). In vitro dissolution studies showed comparable drug release between WT2 and RT at pH 1.2 and 4.0, whereas WT2 exhibited slower, though still complete, dissolution at pH 6.8. Despite these differences, pharmacokinetic studies demonstrated comparable systemic exposure under both fasted and fed conditions. The geometric mean ratios and 90% confidence intervals for maximum plasma concentration (Cmax) and area under the plasma concentration–time curve from time zero to the last quantifiable concentration (AUClast) met conventional bioequivalence criteria. Food intake slightly delayed absorption but had no significant effect on the extent of exposure. This research shows that differences in dissolution arising from pH-dependent solubility did not meaningfully affect systemic exposure of Tofa free base under the studied conditions.

Graphical Abstract