Caffeine-oxalic acid cocrystal, widely reported to be stable under high humidity, dissociated in the presence of numerous pharmaceutical excipients. In cocrystal-excipient binary systems, the water mediated dissociation reaction occurred under pharmaceutically relevant storage conditions. Powder X-ray diffractometry was used to identify the dissociated products obtained as a consequence of coformer-excipient interaction. The proposed cocrystal dissociation mechanism involved water sorption, dissolution of cocrystal and excipient in the sorbed water, proton transfer from oxalic acid to the excipient, and formation of metal salts and caffeine hydrate. In compressed tablets with magnesium stearate, the cocrystal dissociation was readily discerned from the appearance of peaks attributable to caffeine hydrate and stearic acid. Neutral excipients provide an avenue to circumvent the risk of water mediated cocrystal dissociation.

No abstract

No abstract

Caffeine−glutaric acid cocrystal polymorphs, Form I and Form II, are presented as a model system to study cocrystal dissociation under controlled humidity. On the basis of relative humidity (RH) data, it was observed that Form I transforms to Form II at high RH and that the rate of the polymorphic phase transformation increases with increasing RH, with the relative stability of the cocrystal following a trend similar to that of the coformer deliquescence point for other caffeine dicarboxylic acid cocrystals. In addition, reduction in particle size, change in crystal morphology with greater number of crystal faces exposed to surrounding atmosphere, and internal arrangement of molecules in the crystal structure are shown to influence cocrystal instability and favor dissociation under increased humidity.

No abstract