title: Solid Forms of Tenofovir Disoproxil Fumarate, Their Mutual Conversion, and Stabilization of Form I in Formulation.
abstract: Tenofovir disoproxil fumarate (TDF, form I) is an orally delivered pharmaceutical salt used for the treatment of HIV and chronic hepatitis, which acts as an inhibitor of nucleotide reverse transcriptase. There are many solid forms of TDF described in the literature; 2 of them were identified in the drug products: form I and form A. It seems that during formulation, the active pharmaceutical ingredient undergoes partial to total conversion of TDF form I to TDF form A. The goals of this study were to investigate when and why did the conversion occur and whether the conversion could be avoided and how. The influence of pH and possible interaction with excipients were studied. The conditions enabling using wet granulation in technology while preventing the undesired conversion were found. The stabilization was achieved either by replacement of used disintegrants or by acid addition to the current composition of formulation.
authors: Department of Solid State Chemistry, University of Chemistry and Technology Prague, Prague 6, Czech Republic 16628; Solid State Department, Zentiva, k.s., Prague 10, Czech Republic 10237. Electronic address: sladkovv@vscht.cz.
authors: Veronika
authors: V
authors: Sládková
authors: Solid State Department, Zentiva, k.s., Prague 10, Czech Republic 10237.
authors: Ondřej
authors: O
authors: Dammer
authors: Department of Solid State Chemistry, University of Chemistry and Technology Prague, Prague 6, Czech Republic 16628.
authors: Bohumil
authors: B
authors: Kratochvíl
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000378:metabolism*; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D000068698:Tenofovir / Q000737:chemistry* / Q000378:metabolism*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D019380:Anti-HIV Agents; D005079:Excipients; D000068698:Tenofovir
keywords: X-ray powder diffractometry; cocrystals; crystal polymorphism; drug-excipient interaction; formulation