Direct Measurement of Amorphous Solubility
2019
Amorphous materials exhibit distinct physicochemical properties compared to their respective crystalline counterparts. One of these properties, the increased solubility of amorphous materials, is exploited in the pharmaceutical industry as a way of increasing bioavailability of poorly water-soluble drugs. Despite the increasing interest in drug amorphization, the analytical physicochemical toolbox is lacking a reliable method for direct amorphous solubility assessment. Here, we show, for the first time, a direct approach to measure the amorphous solubility of diverse drugs by combining optics with fluidics, the single particle analysis (SPA) method. Moreover, a comparison was made to a theoretical estimation based on thermal analysis and to a standardized supersaturation and precipitation method. We have found a good level of agreement between the three methods. Importantly, the SPA method allowed for the first experimental measurement of the amorphous solubility for griseofulvin, a fast crystallizing dru...
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