Preparation and Properties of New Co-Crystals of Ibandronate with Gluco- or Galactopyranoside Derivatives

Abstract

Mixtures of ibandronate monosodium salt with eleven gluco- and/or galacto-pyranoside derivatives as counterions were designed to prepare co-crystals with improved intestinal absorption. In general, gastrointestinal absorption of bisphosphonates after oral administration is approximately 1%. Co-crystals were generated by means of thermodynamically and/or kinetically controlled crystallization processes. Seventy-seven prepared samples were analyzed by means of FT-NIR, FT-Raman spectrometry and solid state NMR spectroscopy. New entities of ibandronate monosodium salt with phenyl-β-d-galactopyranoside were found and characterized. The absorption of these potential new co-crystals was investigated by means of PAMPA experiments. In the present study the relationships between the chemical structures of the studied compounds required for co-crystal generation are discussed.

Phenyl galactopyranosides – 13 C CPMAS NMR and conformational analysis using genetic algorithm

“…However, contrary to expectation, the evaluated co-crystals showed relatively low bioavailability [18]. Binding of a-and b-D-galactopyranosides with different hydrophobic aglycones to lactose permease of E. coli was compared [18]. The most potent new compound appeared to be m-nitrophenyl-a-D-galactopyranoside.…”

“…Only phenyl b-D-galactopyranoside yielded potential co-crystals with ibandronate probably due to cis-orientation of phenoxy moiety. However, contrary to expectation, the evaluated co-crystals showed relatively low bioavailability [18]. Binding of a-and b-D-galactopyranosides with different hydrophobic aglycones to lactose permease of E. coli was compared [18].…”

Investigation of Carbohydrates and Their Derivatives as Crystallization Modifiers

“…6, structure IV) or risedronate (see Fig. 6, structure V) with a number of carbohydrates as co-crystal formers (Jampílek et al, 2009;Haroková, 2010;Havelková, 2010;Hrušková, 2010;Jampílek et al, 2010;Kos et al, 2011;Ťažká 2011;Havelková, 2012;Oktábec, 2012). The present study deals with the design and an effort to prepare co-crystals/new entities, generally new solid phases, of the above discussed bisphosphonates III-V.…”

“…All generated solid compounds were subsequently screened by means of FT-NIR and FT-Raman spectroscopy. If a sample differing from the starting materials was found, it was additionally characterized by the below mentioned methods (Jampílek et al, 2009;Haroková, 2010;Havelková, 2010;Hrušková, 2010;Jampílek et al, 2010;Kos et al, 2011;Ťažká 2011;Havelková, 2012;Oktábec, 2012). Figure 11.…”

“…Mixtures of BPs and carbohydrates in different ratios and under various conditions were prepared. All the prepared mixtures (solid compounds) were characterized using some of the above mentioned solid state analytical techniques (Haroková, 2010;Havelková, 2010;Hrušková, 2010;Kos et al, 2011;Ťažká 2011;Havelková, 2012;Oktábec, 2012). …”