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.

Risedronate adsorption on bioactive glass surface for applications as bone biomaterial

“…c c e p t e d M a n u s c r i p t of other compound Q RIS1 (compound present in the 31 P MAS-NMR spectra of risedronates) at a chemical displacement to 19 ppm and with a proportion of 7%. This result is in agreementwith the other studies[32] …”

Preparation of Risedronate Nanoparticles by Solvent Evaporation Technique

“…For example, the use of ethylenediaminetetraacetic acid in BP formulations enhanced their absorption in intestine [19]. Other approaches to the modification of BP properties are the preparation of co-crystals [20,21] or the preparation of chitosan-coated mucoadhesive liposomes or peptide prodrugs that can be recognized by the intestine carrier system and subsequently transported. Also, an adduct of risedronate with titanium dioxide particles was proposed as a controlled-release system [22].…”

“…This contribution is a follow-up paper to our previous studies [20,21,23,24,25] and deals with preparation of nanoparticles of risedronate monosodium salt by means of the solvent evaporation method. A solution of excipient is mixed under continuous stirring with a solution of the drug substance and then the second solvent is evaporated.…”

Preparation of Risedronate Nanoparticles Using Selected Polymeric Excipients

“…Also titanium dioxide particles were prepared for the controlled release system of risedronate [12]. Other approach to modification of risedronate properties was preparation of co-crystals [13]. The problem of poor permeability can be also solved by preparation of nanoparticles.…”

“…Nanoparticles can be used for permeation through blood brain barrier [14][15][16]. This contribution is a follow-up paper to our previous studies [13,17,18] and deals with preparation of nanoparticles of risedronate monosodium salt. Nanoparticles are stabilized by polyethylene glycol (macrogol) or carboxymethyl dextran sodium saltexcipients selected based on the GRAS (Generally Recognized as Safe) list, which means that they are not toxic for human body.…”