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Accelerated Stability Assessment Program to Predict Long-term Stability of Drugs: Application to Ascorbic Acid and to a Cyclic Hexapeptide

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Abstract

During pharmaceutical development, the stability of the product is assessed during long-term study. If any stability issues are discovered at this point of the process, it will result in re-formulation and important loss of time and cost. Therefore, important efforts are made in order to select the most stable product. Nevertheless, predicting the stability of the developed product at early stage of the development is challenging. Accelerated stability assessment program (ASAP), based on modified Arrhenius equation and isoconversion approach, appears as an interesting tool allowing to evaluate stability and shelf-life of pharmaceutical product in a short period of time. Nevertheless, few studies using these approaches are published in the literature, and the majority concern small drug molecules. Here, this approach was applied on a small drug molecule, ascorbic acid (AA), and on a cyclic hexapeptide named cFEE. AA and cFEE have been exposed to various temperatures for a maximum of 3 weeks, and then analyzed by capillary electrophoresis coupled to UV detection (CZE-UV) for AA or LC–MS for cFEE. The level of major degradation products was used to build ASAP models and predict the stability of both compounds. Comparison between predicted and long-term data were found accurate for both compounds undergoing two different degradation pathways (oxidation and hydrolysis), confirming the real interest of accelerated predicting stability approach for consistent determination of long-term stability shelf-life of pharmaceutical products.

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Acknowledgements

The authors would like to thank the Pr Jean-Philippe Wolf for kindly providing us with the hexapeptide cFEE.

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Authors and Affiliations

  1. Faculté de Sciences Pharmaceutiques Et Biologiques, Unité de Technologies Chimiques Et Biologiques Pour La Santé (UTCBS), Université de Paris, CNRS UMR8258, Inserm U1022, Paris, France

    Pauline Legrand, Rabah Gahoual  & Pascal Houzé

  2. Département Recherche Et Développement Pharmaceutique, Agence Générale Des Equipements Et Produits de Santé (AGEPS), Assistance Publique–Hôpitaux de Paris, (AP-HP), 7 rue du fer à moulin, 75005, Paris, France

    Pauline Legrand & Sophie Dufaÿ

  3. Service de Biochimie Générale, Hôpital Universitaire Necker-Enfants Malades, Paris, France

    Pascal Houzé

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  1. Pauline Legrand
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  2. Rabah Gahoual
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  3. Pascal Houzé
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  4. Sophie Dufaÿ
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Contributions

Pauline Legrand: Analysis, investigation, methodology, validation, and writing: original draft.

Rabah Gahoual: Investigation, supervision, and writing: review and editing

Pascal Houzé: Resources, supervision, and writing: review and editing

Sophie Dufaÿ: Methodology, resources, supervision, and writing: review and editing

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Correspondence to Pauline Legrand.

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The authors declare no competing interests.

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Legrand, P., Gahoual , R., Houzé, P. et al. Accelerated Stability Assessment Program to Predict Long-term Stability of Drugs: Application to Ascorbic Acid and to a Cyclic Hexapeptide. AAPS PharmSciTech 22, 234 (2021). https://doi.org/10.1208/s12249-021-02121-8

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