title: From a binary salt to salt co-crystals of antibacterial agent lomefloxacin with improved solubility and bioavailability.
abstract: The cocrystallization of lomefloxacin (Lf) with barbituric acid (HBA) and/or isophthalic acid (H2ip) leads to novel binary and ternary salts via hydrogen-bonding recognition. X-ray single-crystal diffraction analyses show that zwitterionic lomefloxacin can adjust itself to fulfill a different supramolecular array in either binary salts or ternary salt co-crystals, formulated as [HLf]·[Hip]·H2O (1), [HLf]·[BA]·[HBA]·H2O (2) and [HLf]·[BA]·[H2ip]·CH3OH·H2O (3). These pharmaceutical agents present uniform charge-assisted hydrogen-bonding networks between HLf cations and acidic coformers with the lattice capturing water molecules. Structural comparison of (2) and (3) indicated that a delicate balance of geometries and hydrogen-bonding partners is required for stacking to favor the formation of ternary salt co-crystals. Cocrystallization was able to overcome the water insolubility of lomefloxacin. Both the salt co-crystals display enhanced solubility and better pharmaceutical applicability.
authors.affiliation: Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, Changzhou University, Changzhou 213164, People's Republic of China.
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, Changzhou University, Changzhou 213164, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, Changzhou University, Changzhou 213164, People's Republic of China.
authors.forename: Qing-Qing
authors.initials: QQ
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, Changzhou University, Changzhou 213164, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, Changzhou University, Changzhou 213164, People's Republic of China.
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: He
authors.affiliation: Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, Changzhou University, Changzhou 213164, People's Republic of China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou 213164, People's Republic of China.
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Song
authors.affiliation: Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, People's Republic of China.
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Xuan
authors.affiliation: School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou 213164, People's Republic of China.
authors.forename: Xian-Feng
authors.initials: XF
authors.lastname: Huang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D024841:Fluoroquinolones / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D012492:Salts / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D053719:Tandem Mass Spectrometry
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D012492:Salts; C053091:lomefloxacin
keywords: active pharmaceutical ingredients (APIs); cocrystallization; lomefloxacin; salt co-crystals; solubility