title: Crystallization products of risedronate with carbohydrates and their substituted derivatives.
abstract: The gastrointestinal absorption of bisphosphonates is in general only about 1%. To address this problem mixtures of risedronate monosodium salt with twelve varied sugar alcohols, furanoses, pyranoses and eight gluco-, manno- and galactopyranoside derivatives as counterions were designed in an effort to prepare co-crystals/new entities with improved intestinal absorption. Crystalline forms were generated by means of kinetically and/or thermodynamically controlled crystallization processes. One hundred and fifty-two prepared samples were screened by means of FT-NIR and FT-Raman spectroscopy. No co-crystal was prepared, but noteworthy results were obtained. A new solid phase of risedronate monosodium salt generated in the presence of phenyl-β-d-galactopyranoside under thermodynamically controlled crystallization conditions was found and also characterized using solid state NMR spectroscopy, X-ray powder diffraction and differential scanning calorimetry. This new polymorph was named as form P. Interactions between risedronate monosodium salt and both carbohydrates were confirmed by means of molecular dynamics simulation. In the present study the relationships between the chemical structures of the studied compounds required for crystalline form change are discussed.
authors.affiliation: Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 61242 Brno, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Kos
authors.forename: Monika
authors.initials: M
authors.lastname: Pentakova
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Oktabec
authors.forename: Lukas
authors.initials: L
authors.lastname: Krejcik
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Mandelova
authors.forename: Pavla
authors.initials: P
authors.lastname: Harokova
authors.forename: Jana
authors.initials: J
authors.lastname: Hruskova
authors.forename: Tomas
authors.initials: T
authors.lastname: Pekarek
authors.forename: Ondrej
authors.initials: O
authors.lastname: Dammer
authors.forename: Marcela
authors.initials: M
authors.lastname: Tkadlecova
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Havlicek
authors.forename: Jarmila
authors.initials: J
authors.lastname: Vinsova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kral
authors.forename: Jiri
authors.initials: J
authors.lastname: Dohnal
authors.forename: Josef
authors.initials: J
authors.lastname: Jampílek
mesh_terms: D002152:Calorimetry, Differential Scanning; D002241:Carbohydrates / Q000737:chemistry*; D003460:Crystallization; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D005697:Galactosides / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D000068296:Risedronic Acid; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D014961:X-Ray Diffraction
chemical_list: D002241:Carbohydrates; D005697:Galactosides; C046399:phenyl-D-galactopyranoside; D000068296:Risedronic Acid; D012968:Etidronic Acid