ABSTRACT
Single crystal structure experiments revealed that the orthorhombic needles of Ciclesonide crystallized in P2(1)2(1)2(1) space group with four independent molecules in the unit cell. Amorphous Ciclesonide was prepared by lyophilization and characterized in comparison with crystalline material by differential scanning calorimetry (DSC), Fourier transformed (FT)-Raman spectroscopy, powder X-ray diffraction, dissolution, and saturation solubility experiments. Significant differences in the dissolution, thermal, and spectrometric behavior were observed for both solid-state phases. DSC- and FT-Raman methods for the determination of amorphous content in crystalline Ciclesonide samples were established. Isothermal and dynamical recrystallization studies on amorphous Ciclesonide were conducted using dispersive hot-stage Raman microscopy. The recrystallization was observed to be a two-step process with an induction period (most likely nuclei formation) followed by the actual recrystallization (crystal growth). The recrystallization rate constants and Avrami exponents (n = 2) were determined from the isothermal experiments at various temperatures using Johnson-Mehl-Avrami theory. Isothermal activation energies were obtained from Arrhenius plots using the temperature dependence of (a) the rate constants (160.4 kJ/mol) and (b) the induction time (140.9 kJ/mol) of the isothermal hot-stage experiments.
Subject(s)
Anti-Allergic Agents/chemistry , Pregnenediones/chemistry , Calorimetry, Differential Scanning , Crystallization , Crystallography, X-Ray , Molecular Structure , Solubility , Spectroscopy, Fourier Transform Infrared , Spectrum Analysis, RamanABSTRACT
In addition to the established control of acid secretion of the class of proton pump inhibitors (PPI) reactivity from the pyridyl methyl sulphinyl benzimidazole type a second independent anti-inflammatory reactivity was observed in vitro. This inhibitory reactivity was clearly noticed using three different assays where the aggressive hydroxyl radicals were successfully trapped in a concentration dependent manner. There is unequivocal evidence that the proton pump inhibitors having the sulphoxide group are able to scavenge hydroxyl radicals which are generated during a Fenton reaction. By way of contrast, the corresponding thioethers were substantially less active. No detectable effect was seen in the superoxide radical scavenging system. In conclusion, pantoprazole as well as the other proton pump inhibitors have a pronounced inhibitory reactivity towards hydroxyl radicals.
Subject(s)
Benzimidazoles/chemistry , Free Radical Scavengers/chemistry , Hydroxyl Radical/chemistry , Omeprazole/analogs & derivatives , Proton Pumps/chemistry , Sulfoxides/chemistry , 2-Pyridinylmethylsulfinylbenzimidazoles , Animals , Cattle , Copper Sulfate/chemistry , Deoxyribose/chemistry , Enzyme Inhibitors/chemistry , Erythrocytes , Heme/chemistry , Hyaluronic Acid/chemistry , Iron Compounds/chemistry , Lansoprazole , Omeprazole/chemistry , Pantoprazole , Sulfides/chemistryABSTRACT
The solution structure of a recombinant mutant [rSP-C (FFI)] of the human surfactant-associated protein C (hSP-C) in a mixture of chloroform and methanol was determined by high-resolution NMR spectroscopy. rSP-C (FFI) contains a helix from Phe5 to the C-terminal Leu34 and is thus longer by two residues than the helix of porcine SP-C (pSP-C), which is reported to start at Val7 in the same solvent. Two sets of resonances at the C-terminus of the peptide were observed, which are explained by low-order oligomerization, probably dimerization of rSP-C (FFI) in its alpha-helical form. The dimerization may be induced by hydrogen bonding of the C-terminal carboxylic groups or by the strictly conserved C-terminal heptapeptide segment with a motif similar to the GxxxG dimerization motif of glycophorin A. Dimerization at the heptapeptide segment would be consistent with findings based on electrospray ionization MS data, chemical cross-linking studies, and CNBr cleavage data.