title: Improving the dissolution and bioavailability of 6-mercaptopurine via co-crystallization with isonicotinamide.
abstract: 6-Mercaptopurine (6-MP) is a clinically important antitumor drug. The commercially available form was provided as monohydrate and belongs to BCS class II category. Co-crystallization screening by reaction crystallization method (RCM) and monitored by powder X-ray diffraction led to the discovery of a new co-crystal formed between 6-MP and isonicotinamide (co-crystal 1). Co-crystal 1 was thoroughly characterized by X-ray diffraction, FT-IR and Raman spectroscopy, and thermal analysis. Noticeably, the in vitro and in vivo studies revealed that co-crystal 1 possesses improved dissolution rate and superior bioavailability on animal model.
authors: Pharmaceutical Analytical & Solid-State Chemistry Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors: Jian-Rong
authors: JR
authors: Wang
authors: Pharmaceutical Analytical & Solid-State Chemistry Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Nano Science and Technology Institute, University of Science and Technology of China, Suzhou, Jiangsu 215123, China.
authors: Xueping
authors: X
authors: Yu
authors: Pharmaceutical Analytical & Solid-State Chemistry Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors: Chun
authors: C
authors: Zhou
authors: Center for Drug Safety Evaluation & Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors: Yunfei
authors: Y
authors: Lin
authors: Jiangsu University, Zhenjiang 212013, China.
authors: Chen
authors: C
authors: Chen
authors: Center for Drug Safety Evaluation & Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: gypan@cdser.simm.ac.cn.
authors: Guoyu
authors: G
authors: Pan
authors: Pharmaceutical Analytical & Solid-State Chemistry Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: xuefengmei@simm.ac.cn.
authors: Xuefeng
authors: X
authors: Mei
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000097:blood / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D015122:Mercaptopurine / Q000097:blood / Q000737:chemistry*; D008958:Models, Molecular; D009536:Niacinamide / Q000737:chemistry*; D033362:Powder Diffraction; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D014961:X-Ray Diffraction
chemical_list: D000964:Antimetabolites, Antineoplastic; D009536:Niacinamide; C027681:isonicotinamide; D015122:Mercaptopurine
keywords: 6-Mercaptopurine; Bioavailability; Crystal structure; Pharmaceutical co-crystal