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• W1975237618 startingPage "1139" @default.
• W1975237618 abstract "Amorphous states, ubiquitous in pharmaceutical products, possess higher tendency for chemical degradation in comparison to crystalline materials. This instability can be further enhanced by water, which is present even in nominally dry systems. It has been increasingly recognized that in addition to the plasticizing effect of lowering the glass transition temperature, water could influence the degradation rates through medium effects (e.g., through change in solvation of the reactants and the transition state) as well as by direct participation in solid-state hydrolytic degradation processes. In the current review, the impact of water on the chemical stability of small molecules is examined, with emphasis on hydrolysis reactions in freeze-dried materials remaining in the glassy state. Quantitative relationships between water content and stability are discussed, including molecular mobility (global and local) and solution-like mechanisms, using the medium effects concept that has been developed for liquid-state reactions. Further progress in this field requires the development of quantitative and mechanistic understanding of the relationship between local mobility and chemical reactivity in amorphous solids, as well as incorporating the learning from solution chemistry on the role of reaction media in chemical processes." @default.
• W1975237618 created "2016-06-24" @default.
• W1975237618 creator A5055615701 @default.
• W1975237618 creator A5088530431 @default.
• W1975237618 date "2013-04-01" @default.
• W1975237618 modified "2023-10-02" @default.
• W1975237618 title "Effect of Water on the Chemical Stability of Amorphous Pharmaceuticals: I. Small Molecules" @default.
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• W1975237618 doi "https://doi.org/10.1002/jps.23440" @default.
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