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Improved Protocol and Data Analysis for Accelerated Shelf-Life Estimation of Solid Dosage Forms

Abstract

Purpose

To propose and test a new accelerated aging protocol for solid-state, small molecule pharmaceuticals which provides faster predictions for drug substance and drug product shelf-life.

Materials and Methods

The concept of an isoconversion paradigm, where times in different temperature and humidity-controlled stability chambers are set to provide a critical degradant level, is introduced for solid-state pharmaceuticals. Reliable estimates for temperature and relative humidity effects are handled using a humidity-corrected Arrhenius equation, where temperature and relative humidity are assumed to be orthogonal. Imprecision is incorporated into a Monte-Carlo simulation to propagate the variations inherent in the experiment. In early development phases, greater imprecision in predictions is tolerated to allow faster screening with reduced sampling. Early development data are then used to design appropriate test conditions for more reliable later stability estimations.

Results

Examples are reported showing that predicted shelf-life values for lower temperatures and different relative humidities are consistent with the measured shelf-life values at those conditions.

Conclusions

The new protocols and analyses provide accurate and precise shelf-life estimations in a reduced time from current state of the art.

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Acknowledgments

The authors would like to acknowledge the assistance of Dr. Julie Lorenz for her helpful discussions and suggestions. The authors would also like to acknowledge the assistance of Yan Liu, Shilpa Naik and Yukun Ren, each of whom contributed to the programming of the Monte-Carlo simulation.

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Correspondence to Kenneth C. Waterman.

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Waterman, K.C., Carella, A.J., Gumkowski, M.J. et al. Improved Protocol and Data Analysis for Accelerated Shelf-Life Estimation of Solid Dosage Forms. Pharm Res 24, 780–790 (2007). https://doi.org/10.1007/s11095-006-9201-4

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  • DOI: https://doi.org/10.1007/s11095-006-9201-4

Key words

  • accelerated aging
  • shelf-life
  • stability