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KMID : 0043320160390050646
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Archives of Pharmacal Research
2016 Volume.39 No. 5 p.646 ~ p.659
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Application of ionic liquid to polymorphic transformation of anti-viral/HIV drug adefovir dipivoxil
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An Ji-Hun
Jin Feng
Kim Hak-Sung
Ryu Hyung-Chul
Kim Jae-Sun
Kim Hyuk-Min
Kiyonga Alice Nguvoko
Min Dong-Sun
Youn Wonn-O
Kim Ki-Hyun
Jung Ki-Won
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Abstract
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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.
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KEYWORD
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Ionic liquid, Polymorphism, Active pharmaceutical ingredient, Polymorphic transformation, Adefovir dipivoxil, Anti-viral/HIV drug
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