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<p>The objectives of the&#xa0;present work were to study the&#xa0;effect of patient-in use and accelerated storage conditions on critical quality attributes (CQAs) of FDA approved varenicline tartrate (VRT) products. Four products (V1, V2, V3 and V4) of VRT were stored at 30&#xa0;°C/75% RH and 40&#xa0;°C/75% RH for three and six months, respectively, and tested periodically for nitrite, impurities (N-nitroso varenicline, N-formyl varenicline and N-methyl varenicline), assay, dissolution and solid-state of the drug. Nitrite content decreased while N-nitroso varenicline increased with storage temperature and duration. Initial nitrite value range was 9.3 ± 2.3 to 31.0 ± 9.3&#xa0;ng/tablet that decreased to 1.7 ± 0.3 to 8.1 ± 5.4&#xa0;ng/tablet after six months storage at 40&#xa0;°C/75%. N-nitroso varenicline, N-formyl varenicline and N-methyl varenicline content ranged from 0–31.0 ± 11, 75 ± 9.1 to 5530.0 ± 1.2, and 7.0 ± 0.3 to 1633.2 ± 55.8&#xa0;ng/tablet after storage, respectively. Polymorphic forms present in V1 and V4 were A and B, respectively, while products V2 and V3 contained amorphous form of the drug. No change in solid state was observed in the products except a decrease in crystallinity of almost 30% after storge. All products completely dissolved &gt; 85% drug in 15&#xa0;min before storage. V1 and V4 showed no significant change in dissolution while product V2 and V3 showed significant decrease in the dissolution. The dissolved drug was 33.6 ± 0.5 and 34.2 ± 0.7% in 30&#xa0;min from V2 and V3 after storage, respectively. In summary, tested products showed differential effects of stability conditions on the CQAs and some of the attributes were critically diminished that need further investigation.</p> Graphical Abstract <p></p>

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Stability Assessment of FDA Approved Varenicline Tartrate Products for Critical Quality Attributes – N-Nitroso Varenicline, Solid Form, and Dissolution

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月9日

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  • Mariame A. Hassan,
  • Gereziher Sibhat,
  • Indra K. Reddy,
  • Mansoor A. Khan,
  • Ziyaur Rahman

摘要

The objectives of the present work were to study the effect of patient-in use and accelerated storage conditions on critical quality attributes (CQAs) of FDA approved varenicline tartrate (VRT) products. Four products (V1, V2, V3 and V4) of VRT were stored at 30 °C/75% RH and 40 °C/75% RH for three and six months, respectively, and tested periodically for nitrite, impurities (N-nitroso varenicline, N-formyl varenicline and N-methyl varenicline), assay, dissolution and solid-state of the drug. Nitrite content decreased while N-nitroso varenicline increased with storage temperature and duration. Initial nitrite value range was 9.3 ± 2.3 to 31.0 ± 9.3 ng/tablet that decreased to 1.7 ± 0.3 to 8.1 ± 5.4 ng/tablet after six months storage at 40 °C/75%. N-nitroso varenicline, N-formyl varenicline and N-methyl varenicline content ranged from 0–31.0 ± 11, 75 ± 9.1 to 5530.0 ± 1.2, and 7.0 ± 0.3 to 1633.2 ± 55.8 ng/tablet after storage, respectively. Polymorphic forms present in V1 and V4 were A and B, respectively, while products V2 and V3 contained amorphous form of the drug. No change in solid state was observed in the products except a decrease in crystallinity of almost 30% after storge. All products completely dissolved > 85% drug in 15 min before storage. V1 and V4 showed no significant change in dissolution while product V2 and V3 showed significant decrease in the dissolution. The dissolved drug was 33.6 ± 0.5 and 34.2 ± 0.7% in 30 min from V2 and V3 after storage, respectively. In summary, tested products showed differential effects of stability conditions on the CQAs and some of the attributes were critically diminished that need further investigation.

Graphical Abstract