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Journal of pharmaceutical sciences

Surface effects on the crystallization of ritonavir glass.


PMID 25382848

Abstract

In our previous study, initiation time of crystallization was shown to be basically expressed as a function of only the reduced temperature, which was a ratio of storage and glass transition temperatures. This conclusion was obtained using quenched glasses with minimized surface area stored under a dried atmosphere. In this study, the surface effects on the crystallization were investigated using freeze-dried ritonavir (RTV) glass. Although quenched RTV glass exhibited exceptionally long initiation time, the initiation was accelerated by using the freeze-dried glasses. Storage of the samples under humid conditions further accelerated the crystallization. These surface effects eliminated the energetic barrier for nucleation, and the RTV glass exhibited universal initiation time. In contrast, subsequent crystal growth was slower for the freeze-dried glasses relative to the quenched one, presumably because of less condensed and porous structures that would suppress molecular cooperativity. Storage under a humid atmosphere also appeared to inhibit the crystal growth, presumably because of disruption of the molecular network by water. These findings support the existence of the universal initiation time for crystallization and indicated the importance of surface effects in crystallization behavior. Also, the suppression of crystal growth because of the void structure and incorporation of water molecules were indicated.