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.

Keywords

• ibandronate
• d-glucopyranosides
• d-galactopyranosides
• co-crystals
• FT-NIR
• FT-Raman
• CP/MAS NMR
• PAMPA