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Purpose <p>There are scarce reports on <i>in vitro</i>-<i>in vivo</i> correlation (IVIVC) model development of immediate-release (IR) formulations, and few investigations of the impacts of formulation and process of spray-dried solid dispersions (SDD)-based tablets on human pharmacokinetics (PK), despite commercial product successes. The goal of this study was to investigate the formulation and process factors that impact bioavailability enhancement of IR itraconazole SDD tablets; and to develop an FDA level A IVIVC that would predict in vivo PK performance from <i>in vitro</i> dissolution testing.</p> Methods <p>A direct, differential-equation-based IVIVC model approach was employed, using an oral solution for post-dissolution disposition and Fast-, Medium-, and Slow-release tablets.</p> Results <p>The IVIVC met FDA internal predictability for level A IVIVC requirements. The <i>in vitro</i> dissolution employed USP simulated intestinal fluid (phosphate buffer), adjusted pH 6.4, and tablets were triturated into particles prior to their immersion into dissolution media to mimic the attenuated disintegration difference between Medium and Slow <i>in vivo</i>. Credibility assessment of the FDA level A IVIVC model was performed, including model verification and validation considerations in light of the question of interest, the context of use, and model risk.</p> Conclusion <p>To our knowledge, this is the first and only study that successfully developed an FDA level A IVIVC of an amorphous solid dispersion, which assessed the impact of grades of the same polymer, disintegrant level, and dry granulation processing on the performance of SDD tablets in humans.</p>

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In Vitro-In Vivo Correlation Of Amorphous Solid Dispersion Enabled Itraconazole Tablets

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月11日

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  • Ana L. Coutinho,
  • Asmita Adhikari,
  • Samuel Krug,
  • Maureen Kane,
  • R. Gary Hollenbeck,
  • Stephen W. Hoag,
  • James E. Polli

摘要

Purpose

There are scarce reports on in vitro-in vivo correlation (IVIVC) model development of immediate-release (IR) formulations, and few investigations of the impacts of formulation and process of spray-dried solid dispersions (SDD)-based tablets on human pharmacokinetics (PK), despite commercial product successes. The goal of this study was to investigate the formulation and process factors that impact bioavailability enhancement of IR itraconazole SDD tablets; and to develop an FDA level A IVIVC that would predict in vivo PK performance from in vitro dissolution testing.

Methods

A direct, differential-equation-based IVIVC model approach was employed, using an oral solution for post-dissolution disposition and Fast-, Medium-, and Slow-release tablets.

Results

The IVIVC met FDA internal predictability for level A IVIVC requirements. The in vitro dissolution employed USP simulated intestinal fluid (phosphate buffer), adjusted pH 6.4, and tablets were triturated into particles prior to their immersion into dissolution media to mimic the attenuated disintegration difference between Medium and Slow in vivo. Credibility assessment of the FDA level A IVIVC model was performed, including model verification and validation considerations in light of the question of interest, the context of use, and model risk.

Conclusion

To our knowledge, this is the first and only study that successfully developed an FDA level A IVIVC of an amorphous solid dispersion, which assessed the impact of grades of the same polymer, disintegrant level, and dry granulation processing on the performance of SDD tablets in humans.