Organic vapor sorption method of isostructural solvates and polymorph of tenofovir disoproxil fumarate

• Published in: European journal of pharmaceutical sciences 2013-11, Vol.50 (3-4), p.253-262
• Main Authors: Lee, Jangmi, Boerrigter, Stephan X.M., Jung, Young Woo, Byun, Youngjoo, Yuk, Soon Hong, Byrn, Stephen R., Lee, Eun Hee
• Format: Article
• Language: English
• Subjects: 2-Propanol - chemistry; Acetonitriles - chemistry; Adenine - analogs & derivatives; Adenine - chemistry; Adsorption; Anti-HIV Agents - chemistry; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Crystallization; Cyclohexanes - chemistry; Ethanol - chemistry; Isostructural desolvate; Isostructural solvate; Organophosphonates - chemistry; Powder Diffraction; Solid-state characterization; Solvents - chemistry; Spectroscopy, Fourier Transform Infrared; Tenofovir; Tenofovir disoproxil fumarate; Thermogravimetry; Toluene - chemistry; Volatilization; X-Ray Diffraction
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2013.07.004

[Display omitted] 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.