Resources


Science of Temperature Impact on Degradation Rates

November 28, 2016
#ASAPprime® and Stability Modeling #FreeThink White Papers

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
#ASAPprime® and Stability Modeling #FreeThink White Papers

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
#ASAPprime® and Stability Modeling #FreeThink White Papers

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
#ASAPprime® and Stability Modeling #FreeThink White Papers

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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Package Selection for Moisture Protection for Solid, Oral Drug Products

November 28, 2016
#ASAPprime® and Stability Modeling

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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Modeling of In-use Stability for Tablets and Powders in Bottles

November 28, 2016
#Customer Presentation/ Publications using ASAPprime®

A model is presented for determining the time when an active pharmaceutical ingredient in tablets/powders will remain within its specification limits during an in-use period; that is, when a heat-induction sealed bottle is opened for fixed time periods and where tablets are removed at fixed time points. This model combines the Accelerated Stability Assessment Program […]

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

November 23, 2016
#ASAPprime® and Stability Modeling

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 […]

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Understanding and Predicting Pharmaceutical Shelf-Life

November 23, 2016
#ASAPprime® and Stability Modeling #Customer Presentation/ Publications using ASAPprime®

In the Handbook of Stability Testing in Pharmaceutical Development, Dr. Ken Waterman discusses how products are assigned a shelf-life which determines the time when a product is considered safe and effective under a relevant storage condition.  A number of factors are used to assign that shelf-life. Click here to access the document.         […]

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A Science-Based Approach to setting Expiry Dating for Solid Drug Products

November 22, 2016
#ASAPprime® and Stability Modeling

This article lays out the basics of new scientific advances in making accurate shelf life determinations for solid drug products using accelerated conditions. Click here to gain access.  

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The Application of the Accelerated Stability Assessment Program (ASAP) to Quality by Design (QbD) for Drug Product Stability

November 22, 2016
#ASAPprime® and Stability Modeling

An isoconversion paradigm, where times in different temperature and humidity-controlled stability chambers are set to provide a fixed degradant level, is shown to compensate for the complex, non-single order kinetics of solid drug products. A humidity-corrected Arrhenius equation provides reliable estimates for temperature and relative humidity effects on degradation rates. A statistical protocol is employed […]

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