title: Application of ionic liquid to polymorphic transformation of anti-viral/HIV drug adefovir dipivoxil.
abstract: Ionic liquids (ILs) are defined as salts with a melting point below 100 °C. ILs have received increasing attention as new alternative to organic solvents because of their unique physicochemical properties. Therefore, this study was conducted in the purpose to present the efficacy of ILs as new solvents capable to control the Polymorphic transformation phenomenon. Here, the polymorphic transformation phenomenon of adefovir dipivoxil, an efficient antiviral active pharmaceutical ingredient on human immunodeficiency virus, was investigated. The phase transformation phenomenon from the metastable polymorph, new form (NF) to the stable polymorph, Form-X in 1-allyl-3-ethylimidazolium tetrafluoroborate (AEImBF4) and 1-butyl-2,3-dimethylimidazolium tetrafluoroborate (BDMImBF4) ILs solutions was observed utilizing the solvent-mediated phase transformation method The thermodynamic factors, AEImBF4/BDMImBF4 solvent composition ratio of 3:7-6:4 and the temperature in range of 25-100 °C, as well as the dynamic factor, the rational speed in range of 300-1000 rpm were parameters studied in this experiment. The thermodynamic and dynamic equations involving nucleation and mass transfer were applied for the quantitative analysis. The result of the present study confirmed the use of ILs as substitute solvent for volatile organic solvents, and demonstrated the efficacy of ILs as potential solvent-media to control the polymorphic transformation.
authors.affiliation: Institute of Pharmaceutical Sciences, College of Pharmacy, CHA University, Sungnam, 13844, Republic of Korea.
authors.forename: Ji-Hun
authors.initials: JH
authors.lastname: An
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan, 54538, Republic of Korea.
authors.forename: Feng
authors.initials: F
authors.lastname: Jin
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan, 54538, Republic of Korea.
authors.forename: Hak Sung
authors.initials: HS
authors.lastname: Kim
authors.affiliation: R&D Center, J2H Biotech, Ansan, 15426, Republic of Korea.
authors.forename: Hyung Chul
authors.initials: HC
authors.lastname: Ryu
authors.affiliation: R&D Center, J2H Biotech, Ansan, 15426, Republic of Korea.
authors.forename: Jae Sun
authors.initials: JS
authors.lastname: Kim
authors.affiliation: R&D Center, J2H Biotech, Ansan, 15426, Republic of Korea.
authors.forename: Hyuk Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Institute of Pharmaceutical Sciences, College of Pharmacy, CHA University, Sungnam, 13844, Republic of Korea.
authors.forename: Alice Nguvoko
authors.initials: AN
authors.lastname: Kiyonga
authors.affiliation: Hankyong Analysis Center, Hankyong National University, Anseong, 17579, Republic of Korea.
authors.forename: Dong Sun
authors.initials: DS
authors.lastname: Min
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongiu, 28644, Republic of Korea.
authors.forename: Wonno
authors.initials: W
authors.lastname: Youn
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea. khkim83@skku.edu.
authors.forename: Ki Hyun
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Institute of Pharmaceutical Sciences, College of Pharmacy, CHA University, Sungnam, 13844, Republic of Korea. pharmj@cha.ac.kr.
authors.forename: Kiwon
authors.initials: K
authors.lastname: Jung
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D019380:Anti-HIV Agents / Q000737:chemistry*; D003460:Crystallization; D004355:Drug Stability; D052578:Ionic Liquids / Q000737:chemistry*; D008962:Models, Theoretical; D063065:Organophosphonates / Q000737:chemistry*; D044367:Phase Transition; D012995:Solubility; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D044366:Transition Temperature
chemical_list: D019380:Anti-HIV Agents; D052578:Ionic Liquids; D063065:Organophosphonates; D012996:Solutions; D000225:Adenine; C106812:adefovir dipivoxil
keywords: Active pharmaceutical ingredient; Adefovir dipivoxil; Anti-viral/HIV drug; Ionic liquid; Polymorphic transformation; Polymorphism