The physicochemical stability of six phenobarbital modifications [forms A, B, C (monohydrate), D (dioxane solvate), E (hemihydrate), and F] at various levels of humidity and temperature were measured using X-ray diffractometry and differential scanning calorimetry. Form D was identified as a new crystalline form (dioxane solvate). Polymorphic transformations of the modifications were investigated by the Kissinger method under nonisothermal conditions. Change of polymorphic content of phenobarbital modifications under various humidity levels at 45 degrees C was evaluated by X-ray powder diffraction. The polymorphic stability under isothermal conditions was estimated kinetically, based upon the Jander equation. Forms A, B, and F were stable at 0 and 75% RH and 45 degrees C for 3 months. On the contrary, forms C, D, and E transformed during storage. The transformation rates of form D were larger than that of forms C and E.

The physicochemical properties of amorphous forms of frusemide, prepared by spray-drying at 50 or 150 degrees C, and their hygroscopic stability at temperatures of 25 and 40 degrees C, and at 0 and 75% relative humidity were investigated. The glass transition temperature of the amorphous form A was 44.2 degrees C as measured by differential scanning calorimetry, while that of the amorphous form B was 54.4 degrees C. The activation energies for glass transition and crystallization processes were calculated from the differential scanning calorimetry thermograms of amorphous forms A and B, respectively. Stability determined by X-ray diffraction at 0% relative humidity, 25 and 40 degrees C suggested that form B was more stable than form A. However, the stability of form A at 75% relative humidity and 25 and 40 degrees C was similar to that of form B.

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Inorganic diphosphonate phosphonylated predominantly phosphate groups on nucleoside 5′-monophosphates (=NMP’s: AMP, GMP, IMP, CMP, and UMP), deoxynudeoside 5′-monophosphates (=dNMP’s: dAMP and dTMP), and sugar phosphates (=SP’s: GlclP, Glc6P, and Rib5P) in aqueous solutions under mild conditions (50–70 °C, pH 6). The chemical structures of phosphonylated products were discussed on their 31P NMR spectra and high-performance liquid chromatograms. The main phosphonylated products from NMP’s and dNMP’s were analogous in structure to nucleoside 5′-diphosphates. The rate of phosphonylation of phosphate groups on NMP’s, dNMP’s, and SP’s varied strongly depending on reaction conditions: pH, reaction temperature, and initial concentration of inorganic diphosphonate. The maximum yields of phosphonylated products were ca. 70% for all NMP’s, dNMP’s, and SP’s under the following conditions: initial concentration of inorganic diphosphonate is 1.5 mol dm−3; each initial concentration of NMP’s, dNMP’s, or SP’s is 0.1 mol dm−3; 70 °C; pH 6.