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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.

Glucagon-induced growth hormone (GH) secretion was studied in healthy subjects under basal conditions (n = 18), and when treated with TRH (n = 10), cyproheptadine (n = 8) and pimozide (n = 6). With glucagon alone, the mean serum GH level significantly increased at 150 minutes and at 180 minutes. TRH administered as a bolus injection completely suppressed the GH response to glucagon. Cyproheptadine pretreatment resulted in a substantial suppression of the GH response to glucagon. A significant difference between basal and post-cyproheptadine GH levels was observed at 150 minutes after glucagon. Pimozide pretreatment was followed by a reduction of GH response to glucagon, but the difference between control and pimozide-treated groups was not significant. In conclusion, it is proposed that glucagon-induced GH secretion is at least partly mediated via serotoninergic mechanisms while significant dopaminergic involvement does not seem probable. It is further suggested that TRH plays a substantial inhibitory role in glucagon-stimulated SH secretion.