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Solubility Enhancement of Ezetimibe by a Cocrystal Engineering Technique
journal contribution
posted on 2014-09-03, 00:00 authored by Kumari Sugandha, Santanu Kaity, Samrat Mukherjee, Jinu Isaac, Animesh GhoshThe present study illustrates the
formation and characterization
of three different cocrystals of ezetimibe using methyl paraben as
a coformer, employing three different processes, namely, solution
crystallization, liquid assisted grinding, and reaction crystallization.
Thermal analysis by differential scanning calorimetry (DSC) and thermogravimetric
analysis were used as a primary analytical tool, followed by spectroscopic
and crystallographic study as a confirmatory analytical tool. Equilibrium
aqueous solubility studies were performed for all cocrystals taking
ezetimibe as the control. The ideal solubility of drug and cocrystals
was also calculated using data obtained from DSC (heat of fusion,
ΔH, and transition melting temperature, Tm). The equilibrium aqueous solubility of ezetimibe
was enhanced by about 2-fold in the case of cocrystal prepared by
solution crystallization. Cocrystals prepared via reaction crystallization
showed solubility that was almost the same as that of pure ezetimibe.
The dissolution profile of all cocrystals, with pure ezetimibe as
a control, was studied for 2 h in defined biorelevant media. Cocrystal
II, prepared by a liquid assisted grinding method, showed significant
improvement in solubility at 45 and 120 min, indicating a good dissolution
profile. The study demonstrates that pharmaceutical cocrystallization
of ezetimibe with methyl paraben can be a possible and potential alternative
and effective approach for improving its solubility.