Resveratrol cocrystals with enhanced solubility and tabletability.
Two new 1:1 cocrystals of resveratrol (RES) with 4-aminobenzamide (RES-4ABZ) and isoniazid (RES-ISN) were synthesized by liquid assisted grinding (LAG) and rapid solvent removal (RSR) methods using ethanol as solvent. Their physiochemical properties were characterized using PXRD, DSC, solid state and solution NMR, FT-IR, and HPLC. Pharmaceutically relevant properties, including tabletability, solubility, intrinsic dissolution rate, and hygroscopicity, were evaluated. Temperature-composition phase diagram for RES-ISN cocrystal system was constructed from DSC data. Both cocrystals show higher solubility than resveratrol over a broad range of pH. They are phase stable and non-hygroscopic even under high humidity conditions. Importantly, both cocrystals exhibit improved solubility and tabletability compared with RES, which make them more suitable candidates for tablet formulation development.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao; Hygiene Detection Center, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangdong, Guangzhou 510515, China.
Zhengzheng
Z
Zhou
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao.
Wanying
W
Li
Department of Pharmaceutics, University of Minnesota, 308 Harvard Street S. E., MN 55455, United States.
Wei-Jhe
WJ
Sun
School of Pharmaceutical Sciences, School of Chemistry and Chemical engineering, Sun Yat-sen University, Guangzhou, China.
Tongbu
T
Lu
School of Health Sciences, Macao Polytechnic Institute, Macao.
Henry H Y
HHY
Tong
Department of Pharmaceutics, University of Minnesota, 308 Harvard Street S. E., MN 55455, United States. Electronic address: sunx0053@umn.edu.
Changquan Calvin
CC
Sun
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao. Electronic address: yzheng@umac.mo.
Ying
Y
Zheng
D001549:Benzamides / Q000737:chemistry; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D033362:Powder Diffraction / Q000379:methods; D000077185:Resveratrol; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013267:Stilbenes / Q000737:chemistry*; D013607:Tablets / Q000737:chemistry*; D013696:Temperature; D014961:X-Ray Diffraction / Q000379:methods; D062366:para-Aminobenzoates / Q000737:chemistry
D001549:Benzamides; D013267:Stilbenes; D013607:Tablets; D062366:para-Aminobenzoates; C041338:4-aminobenzamide; D000077185:Resveratrol
Cocrystal; Mechanical property; Resveratrol (RES); Solubility; Tabletability