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Crystallization Products of Risedronate with Carbohydrates and Their Substituted Derivatives†
Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 612 42 Brno, Czech Republic
Zentiva k.s., U Kabelovny 130, 102 37 Prague 10, Czech Republic
Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic
Faculty of Chemical Engineering, Institute of Chemical Technology, Technicka 5, 16628 Prague 6, Czech Republic
† Preliminary results were presented at the Fourteenth Electronic Conference on Synthetic Organic Chemistry (ECSOC-14, http://www.sciforum.net/presentation/421), 1–30 November 2010.
* Author to whom correspondence should be addressed.
Received: 7 February 2011; in revised form: 11 April 2011 / Accepted: 3 May 2011 / Published: 4 May 2011
(This article belongs to the Special Issue ECSOC-14
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.
Keywords: risedronate; phenyl-β-d-galactopyranoside; polymorph P; FT-NIR; FT-Raman; CP/MAS NMR; XRPD; DSC
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Kos, J.; Pentakova, M.; Oktabec, Z.; Krejcik, L.; Mandelova, Z.; Harokova, P.; Hruskova, J.; Pekarek, T.; Dammer, O.; Tkadlecova, M.; Havlicek, J.; Vinsova, J.; Kral, V.; Dohnal, J.; Jampílek, J. Crystallization Products of Risedronate with Carbohydrates and Their Substituted Derivatives. Molecules 2011, 16, 3740-3760.
Kos J, Pentakova M, Oktabec Z, Krejcik L, Mandelova Z, Harokova P, Hruskova J, Pekarek T, Dammer O, Tkadlecova M, Havlicek J, Vinsova J, Kral V, Dohnal J, Jampílek J. Crystallization Products of Risedronate with Carbohydrates and Their Substituted Derivatives. Molecules. 2011; 16(5):3740-3760.
Kos, Jiri; Pentakova, Monika; Oktabec, Zbynek; Krejcik, Lukas; Mandelova, Zuzana; Harokova, Pavla; Hruskova, Jana; Pekarek, Tomas; Dammer, Ondrej; Tkadlecova, Marcela; Havlicek, Jaroslav; Vinsova, Jarmila; Kral, Vladimir; Dohnal, Jiri; Jampílek, Josef. 2011. "Crystallization Products of Risedronate with Carbohydrates and Their Substituted Derivatives." Molecules 16, no. 5: 3740-3760.