Pharmaceutical Cocrystals of Diflunisal with Nicotinamide or Isonicotinamide
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- 作者：Lianyan Wang ; Bo Tan ; Hailu Zhang ; Zongwu Deng
- 刊名：Organic Process Research & Development
- 出版年：2013
- 出版时间：November 15, 2013
- 年：2013
- 卷：17
- 期：11
- 页码：1413-1418
- 全文大小：327K
- 年卷期：v.17,no.11(November 15, 2013)
- ISSN：1520-586X
文摘
In order to improve the solubility of diflunisal (DIF), and hence the oral bioavailability, two 2:1 diflunisal cocrystals were prepared by solution crystallization from ethanol with nicotinamide (NIC) or isonicotinamide (ISO) as coformer. The cocrystals were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), as well as liquid- and solid-state nuclear magnetic resonance (LNMR and SSNMR). PXRD and NMR measurements indicate that the pure 2:1 cocrystals can be obtained even the DIF and coformer started from different ratios (2:1, 1:1 and 1:2). FTIR and 13C SSNMR measurements provide clues about the formation of amide鈥揷arboxylic acid heterosynthon and pyridine鈥揷arboxylic acid heterosynthon between DIF and coformer. The melting points of DIF-NIC and DIF-ISO cocrystals are 195 and 182 掳C respectively, indicating their favorable thermal stability. Meanwhile, the two cocrystals exhibit faster dissolution rates and higher aqueous solubilities than the pure drug compound.