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Purpose.
Deliquescence is a first-order phase transformation from solid to solution and occurs at a specific relative humidity (RH) that is characteristic to the solid. The goal of this research was to investigate the reduction in critical relative humidity (RH0) in binary solid mixtures of deliquescent active pharmaceutical ingredients (APIs) and deliquescent excipients.
Methods.
The RH where deliquescence is induced, RH0, was measured using a gravimetric water vapor sorption balance. Values were obtained for model deliquescent APIs and excipients as well as for their binary mixtures. Model APIs included ranitidine HCl and diphenhydramine HCl, and sucrose and sodium chloride were examples of excipients investigated. To probe the thermodynamics of this phenomenon, water activity (aw) of various saturated solutions of API and excipient systems was measured using a water activity meter. Optical microscopy was used to observe visually the phenomenon under investigation. The Ross equation was used to estimate RH0mix, and predicted values were compared with experimental results.
Results.
There was close agreement between RH0 measurements (single-component RH0, and RH0mix) and aw measurements of the corresponding saturated solutions. In addition, RH0mix values were always lower than RH0 for the API and excipients alone. In general, experimentally observed RH0mix values were higher than those predicted using the Ross equation.
Conclusions.
Mixtures of deliquescent API and deliquescent excipient are more hygroscopic (i.e., have lower RH0) than either the API or the excipient alone. This might have significant effects on API and drug product stability.
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Salameh, A., Taylor, L. Deliquescence in Binary Mixtures. Pharm Res 22, 318–324 (2005). https://doi.org/10.1007/s11095-005-1563-5
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DOI: https://doi.org/10.1007/s11095-005-1563-5