title: Organic vapor sorption method of isostructural solvates and polymorph of tenofovir disoproxil fumarate.
abstract: Tenofovir disoproxil fumarate (TDF) is a prodrug of tenofovir that belongs to a class of antiretroviral drugs, a nucleotide reverse transcriptase inhibitor. An acetonitrile solvate of TDF I, another new solvated form of TDF, was prepared and solid state characterization of its form was conducted using powder X-ray diffraction, FT-IR spectroscopy, and organic vapor sorption isotherm. During the characterization work, it was discovered that (1) TDF I can form solvates and polymorph with a wide variety of organic solvents as well as water and (2) to different extents, these solvates undergoes anisotropic lattice contraction/expansion during desolvation/solvation process suggesting the formation of isostructural solvates of TDF. Solvents used in this study include ethanol, isopropyl alcohol, acetonitrile, cyclohexane, toluene, and water. Four new solvates using ethanol, isopropyl alcohol, acetonitrile, and toluene vapor and one polymorph using water vapor were discovered. Their solid state characterizations were conducted using powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and Fourier transform infrared spectroscopy. A variety of isostructural solvates and a polymorph of TDF was produced by an organic vapor sorption method, showing varying physicochemical properties. This study demonstrates an alternative crystallization method to obtain isostructural solvates.
authors.affiliation: College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 339-700, Republic of Korea.
authors.forename: Jangmi
authors.initials: J
authors.lastname: Lee
authors.forename: Stephan X M
authors.initials: SX
authors.lastname: Boerrigter
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Jung
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Byun
authors.forename: Soon Hong
authors.initials: SH
authors.lastname: Yuk
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Byrn
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Lee
mesh_terms: D019840:2-Propanol / Q000737:chemistry; D000097:Acetonitriles / Q000737:chemistry; D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D000327:Adsorption; D019380:Anti-HIV Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D003510:Cyclohexanes / Q000737:chemistry; D000431:Ethanol / Q000737:chemistry; D063065:Organophosphonates / Q000737:chemistry*; D033362:Powder Diffraction; D012997:Solvents / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D000068698:Tenofovir; D013818:Thermogravimetry; D014050:Toluene / Q000737:chemistry; D014835:Volatilization; D014961:X-Ray Diffraction
chemical_list: D000097:Acetonitriles; D019380:Anti-HIV Agents; D003510:Cyclohexanes; D063065:Organophosphonates; D012997:Solvents; D014050:Toluene; D000431:Ethanol; C506365:Cyclohexane; D000068698:Tenofovir; D000225:Adenine; D019840:2-Propanol; C032159:acetonitrile
keywords: Isostructural desolvate; Isostructural solvate; Solid-state characterization; Tenofovir disoproxil fumarate