Journal
CRYSTENGCOMM
Volume 17, Issue 3, Pages 612-620Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4ce01921k
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Funding
- NSFC [21101173, 91127002, 21331007]
- NSF of Guangdong Province [S2012030006240]
- Guangzhou Pearl River New Star Fund Science and Technology Planning Project [2013J2200054]
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Pharmaceutical cocrystals have been extensively investigated as a promising approach to improve drugs' physicochemical properties. Cocrystals are usually prepared using solution-mediated methods and grinding methods. In this study, a cocrystal of pimelic acid with poorly soluble melatonin was produced using a melt crystallization method by controlling the crystallization within a specific temperature range. The cocrystal was characterized by infrared spectroscopy, powder and single crystal X-ray diffraction. The binary phase diagram and the formation enthalpy established by differential scanning calorimetry provided the rationale for this spontaneous cocrystallization system. The cocrystal exhibited higher apparent solubility, a faster dissolution rate and acceptable stability as compared to the original melatonin. The study has shown that the melt crystallization method can be considered as a competitive route for producing pharmaceutical cocrystals with improved properties and the thermodynamic investigation can provide in depth understanding and guidance on the melt crystallization of cocrystals.
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