Error Estimation in Accelerating Stability Modeling

December 20, 2016

Methods of predicting the uncertainty in ambient shelf-life (probability of passing a specification limit at a given storage time) from accelerated data using a two-step process (estimation of isoconversion then Arrhenius fitting) were evaluated.  by Kenneth C. Waterman*, Jon T. Swanson, Blake L. Lippold, FreeThink Technologies, Inc. Branford, CT      

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Science of Temperature Impact on Degradation Rates

November 28, 2016

The nature of the temperature dependence on reaction rates is reviewed. The Arrhenius equation is discussed with special attention paid to the two key terms: the activation energy Ea, and collision frequency A. While the latter term is usually considered temperature-independent, we examine this assumption in more detail for gas, liquid and solid states.  In liquid state, collision frequency […]

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Science of Humidity Impact on Degradation Rates in Solids

November 28, 2016

The rate of chemical reactions in multi-component, solid systems such as drug products depends exponentially on the water activity (equilibrium relative humidity).  It is proposed that this dependence is directly linked to an exponential increase in water content as a function of relative humidity at amorphous (non-crystalline) regions.  Such exponential sorption is attributed to cooperative […]

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Why Cross-Terms Between Temperature and RH are Not Useful for ASAPprime®

November 28, 2016

Proposals to add more terms to the modified Arrhenius fitting (with an exponential dependence on reciprocal temperature and water activity) used with ASAPprime® run the risk of over-fitting limited data sets.  Over-fitting of accelerated data is particularly dangerous compared to common DOE optimizations since the optimized parameters are used in extrapolated fitting, where small errors can […]

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A Generalized Relation for Solid-State Drug Stability as a Function of Excipient Dilution: Temperature Independent Behavior

November 28, 2016

A proposed generalized relationship for the impact of excipients on the solid-state chemical stability of drug products is presented and shown to be consistent across multiple degradation products with two example drugs. In this model, when the number of drug particles is comparable to the number of excipient particles, the impact of the excipient on […]

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