Pharmaceutical cocrystals are a novel
drug form with the potential
to enhance pharmaceutical properties, including the solubility and
dissolution behavior for BCS class II drug substances such as indomethacin
(IMC). Recently, we reported that pure indomethacin–saccharin
(IMC–SAC) cocrystals were prepared via anti-solvent crystallization.
In this study, we investigated the solubility behavior of IMC–SAC
cocrystals and individual components in methanol–water cosolvent.
Also, the phase solubility diagram (PSD) of the cocrystal was determined
to increase our understanding of cocrystallization. The criterion
for pure IMC–SAC cocrystal formation was proposed and verified
through supporting experiments performed with different concentrations.
We also found that S
cocrystal and S
cocrystal/S
drug are
critical factors for the design of the cocrystallization process via
anti-solvent addition. Real-time monitoring of the cocrystallization
process was performed using an in-line near-infrared (NIR) system.
Principal component analysis (PCA) was applied to NIR spectral analysis.
Based on the PCA results, distinct differences were observed in the
pathways of IMC–SAC cocrystal formation depending on the initial
concentrations.
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