Physico-chemical Characterization of Hydrated and Anhydrous Crystal Forms of Amlodipine Besylate

The antihypertensive drug substance amlodipine besylate crystallizes in two stable crystal forms, an anhydrate and a hitherto unknown monohydrate. Both forms have been characterized by thermal analysis, X-ray powder diffractometry, FTIR- and FT Raman spectroscopy. Moisture sorption- and desorption investigations reveal their unusual physical stability in a broad range of relative humidities. The monohydrate forms an isomorphic dehydrate upon dehydration, which was elucidated by variable temperature X-ray powder diffractometry. Physico-chemical properties as well as relative stabilities of the crystal forms are described and discussed based on a comprehensive analytical identification, and enable an estimation of practical relevance for manufacturing of amlodipine besylate solid dosage forms. This revised version was published online in August 2006 with corrections to the Cover Date.     

Identification of variant forms of the neuroendocrine peptide galanin

Galanin is a neuroendocrine peptide widely distributed in the central and peripheral nervous systems and in endocrine tissues. Using radioimmunoassays, chromatographic separations, and tandem mass spectrometry, we have identified a series of five variant forms of galanin purified from porcine upper intestine. The modified variants include three beta-aspartyl-shifted forms, an oxidized form containing Trp monooxide, and an N-terminally truncated form. All were found to be C-terminally amidated. At least the beta-aspartyl-shifted forms could be of native occurrence. Mechanistic explanations of the mass spectrometric fragmentation patterns of the different forms are suggested.     

Polymers in the formulation of drug dosage forms with modified release

New polymer-based dosage forms with specified biopharmaceutical properties, including dosage forms with modified release, are described. The mechanism and character of release of active pharmaceutical ingredients from the dosage forms are discussed.     

Theoretical Investigation of the Prototropic Diad Rearrangement of Salicylphosphorous and Phthalimidophosphorous Acids

The structures and energies of the tautomeric forms of salicylphosphorous and phthalimidophosphorous acids have been calculated by the DFT method. The tautomeric forms are found to be in equilibrium. Both tautomeric forms of phthalimidophosphorous acid may have an intramolecular hydrogen bond.     

Quantum chemical studies on tautomerism of 2-, 3- or 4-hydroxyquinoline derivatives along with their thio and azo analogs

The geometries, relative stabilities and proton affinities for the different tautomers of 2-, 3- and 4-hydroxyquinoline derivatives and their thio and azo analogs along with their fixed forms (i.e. model molecules in which the proton migration is eliminated) were calculated with full geometry optimization using AM1, PM3 and MNDO methods. The predominance of oxo forms over hydroxy forms were confirmed with all three methods both in gas and liquid phases, as cited in the literature, with the exception of 3-hydroxyquinoline for which the AM1 and MNDO methods both in gas and liquid phases suggest the predominance of the hydroxy form. For the thio analogs the predominance of thione forms over mercapto forms and for the amino analogs the predominance of the amino forms over imino forms were confirmed both in gas and liquid phases with all three methods as indicated in the literature.     

Non-empirical SCF MO studies on the protonation of biopolymer constituents

Proton affinities of several of the tautomeric forms of cytosine and thymine have been calculated using theab initio Hartree-Fock-Roothaan SCF method. Several of the most stable protonated forms may be obtained by direct protonation from one of the two most stable neutral forms. The calculated total energies do not exclude the possibility of the coexistence of several protonated forms in acidic solutions.     

The thermodynamic characteristics of processes in Raney nickel surface layers with the participation of adsorbed hydrogen forms

Equilibria between adsorbed hydrogen forms on the surface of Raney nickel in aqueous solutions were studied by the potentiometric and adsorption-calorimetric methods. The establishment of equilibria between adsorbate forms was proved experimentally. The model of a surface with discrete inhomogeneity was used to determine the standard thermodynamic characteristics of surface equilibria and adsorption of particular hydrogen adsorption forms. The influence of pH of the bulk phase on the thermodynamic characteristics of adsorption of hydrogen on the surface of Raney nickel caused redistribution of adsorbed hydrogen forms.     

Tunneling effects of dyadic prototropic rearrangement of hypophosphorous acid

The structures and energies of the tautomeric forms of hypophosphorous acid and phosphine oxide were calculated by DFT. The tautomeric forms are in equilibrium, and intramolecular hydrogen bonding is shown to be possible in both tautomeric forms of phthalimidophosphorous acid. The equilibrium constants are estimated within a wide temperature range. The necessity to take into account the tunneling contribution to the rate constant of the rearrangement is demonstrated.     

Use of lignosulfonates in newsprint paper production

A short overview of the most prospective applications of industrial lignosulfonates in various industries, such as newsprint paper production, is presented. Lignosulfonates can be utilized in technological processes in various forms, including (1) forms immobilized by paper components and (2) chemically modified forms used as functional additives to the composition of paper-making stock.     

Structural comparisons of the aggregates of tobacco mosaic virus protein

The coat protein of tobacco mosaic virus forms numerous aggregates, including the small A-protein, the disk, and two helical forms. The structures of the disk, the helical protein forms, and the virus are compared. Most of the differences are in the conformation of the chain between residues 89 and 113, which lies in the region of protein at the center of the virus, inside the RNA. It is disordered in the disk, but has a fixed conformation in the virus and the protein helices. The differences between the virus and the two helical protein forms are largely in the conformations of arginines and carboxylic acids in this region.     

A tale of two polymorphic pharmaceuticals: pyrithyldione and propyphenazone and their 1937 co-crystal patent

A co-crystal of two polymorphic active pharmaceutical ingredients (APIs), first reported and patented in 1937, has been prepared and thoroughly characterised, including crystal structure analysis. The existence of four crystal forms of one of the APIs, the sedative and hypnotic active pharmaceutical ingredient 3,3-diethyl-2,4(1H,3H)-pyridinedione, pyrithyldione (PYR), and of three crystal forms of the co-crystal-forming second API, the non-steroidal anti-inflammatory drug 1,2-dihydro-1,5-dimethyl-4-(1-methylethyl)-2-phenyl-3H-pyrazol-3-one, propyphenazone (PROP), has been reported previously, but they have only been partly characterised. For both compounds, none of the metastable forms exist at room temperature. DSC, hot-stage microscopy, X-ray diffraction and powder synchrotron X-ray diffraction were employed to characterise the polymorphic forms and to determine the crystal structures of forms I-III of PYR and forms I and II of PROP.     

Vibrational spectra of hexagonal crystalline polyoxymethylene

Infrared and Raman spectra of two hexagonal crystalline forms of polyoxymethylene were measured, and the characteristic infrared bands have been determined. The Raman spectra of these two forms do not differ. The vibrational spectra of both forms can be explained by the occurrence of defects in the helical structure of one of them.     

Stability of the normal, zwitterionic neutral and anionic forms of aspartic acid in gas phase and aqueous media

Aspartic acid has a place of special importance among amino acids in view of its property to racemize from the - to the -form in living and nonliving systems which can be used to determine age. Molecular geometries of two isomeric normal neutral forms (called A and B forms), isomeric zwitterionic neutral forms (called A(Z) and B(Z) forms) and anions of these forms of aspartic acid were optimized at the RHF/6-31+G^* level. The geometries of hydrogen bonded complexes of each of the above species with one, two and three water molecules were also optimized at the same level. All these systems were solvated in bulk water using the polarized continuum model (PCM) of the self-consistent reaction field (SCRF) theory at the RHF/6-31+G^* level using the gas phase optimized geometries. It is found that in gas phase, the normal neutral A and B forms of aspartic acid would coexist while the zwitterionic A(Z) and B(Z) forms of the same would be absent. On the other hand, in bulk aqueous media, the normal neutral A and B forms of aspartic acid would not occur while the zwitterionic A(Z) and B(Z) forms would be present. Further, the abundance of the A(Z) form would be much more than that of the B(Z) form in bulk water. If the solution pH is adjusted appropriately so that a monoanion is formed, the anion of aspartic acid obtained from the neutral zwitterionic form by deprotonating O₈ would occur dominantly.     

Influence of the molecular structure and the nature of the solvent on the absorption and fluorescence characteristics of rhodamines

A study of the equilibrium of the molecular forms of rhodamine 19 in aqueous and ethanolic solution is carried out by determining the absorption and fluorescence characteristics of the zwitterionic and the cationic forms of the dye. The optical properties of rhodamine 19 are compared with those obtained for rhodamine 6G and also with those previously reported for rhodamine 3B and for the molecular forms of rhodamine B in water and ethanol. Different aspects of the molecular structure of the rhodamines and solvent effects are discussed, as well as their influence on the photophysical properties of the rhodamines. The aggregation of the molecular forms of rhodamine 19 is also studied in water and ethanol.     

Thermogravimetric investigation of the alkaline earth diliturates

Thermolysis curves for calcium, strontium and barium diliturates were obtained. Calcium dilituratc forms an octahydrate from aqueous solution while strontium, dilituratc forms a. heptahydrate and barium diliturate forms a tetrahydrate.Methods for the thermogravimetrie determination of strontium and barium were developed and found to be quite accurate; calcium can only be determined semi-qnartitatively by precipitation as the diliturate salt.     

Improved separation of metallothionein isoforms by the presence of cyclodextrin in capillary zone electrophoresis

Capillary zone electrophoresis (CZE) with cyclodextrin (CD) in the polyacrylamide-coated capillary was used to study metallothionein (MT) forms in the horse kidney preparation produced commercially by Sigma. It is known that CDs form complexes with hydrophobic amino acids. The results show that the presence of CD improves the separability of the various MT forms, including the MT-IA and the MT-IB forms, metallothionein aggregates, as well as the so far unidentified a and b forms. This was true both below and above the isoelectric points (pIs), although the migration times were somewhat longer at increasing CD concentrations for runs at constant voltage than with constant current.     

Detection of the reduced forms of radical adducts on the ESR trace using HPLC‐electrochemical detector‐ultraviolet absorption detector‐electron spin resonance‐MS

To detect and identify the electron spin resonance (ESR) silent forms of the α‐(4‐pyridyl‐1‐oxide)‐N‐tert‐butylnitrone (4‐POBN) radical adducts, an electrochemical detector (ECD) was employed as a reactor in the HPLC‐ECD‐UV absorption detector‐ESR‐MS (HPLC‐ECD‐UV‐ESR‐MS). The ECD was employed to regenerate the radical forms from the reduced forms. The reduced forms of the 4‐POBN/pentyl radical adducts were analyzed using the HPLC‐ECD‐UV‐ESR‐MS. On addition of the ECD applied potential of +0.3 V, a peak appeared on the ESR trace of the HPLC‐ECD‐UV‐ESR‐MS analyses, indicating that the radical forms are regenerated from the reduced forms. The HPLC‐ECD‐UV‐ESR‐MS analyses were also performed for the reaction mixtures of phenylhydrazine with CuCl₂. Two peaks (peaks I and II) were detected on the UV trace (300 nm) of the HPLC‐ECD‐UV‐ESR‐MS. The mass spectra showed that the peak I and peak II compounds are radical and reduced forms of the 4‐POBN/phenyl radical adducts under the ECD applied potential of 0.0 V. Peak I was only detected on the ESR trace under the ECD applied potential of 0.0 V. In addition to peak I, peak II appeared on the ESR trace under the ECD applied potential of +0.3 V, indicating that the reduced forms are oxidized to the corresponding radical forms.     

Ultrafast photoisomerization of photoactive yellow protein chromophore analogues in solution: influence of the protonation state.

We investigate solvent viscosity and polarity effects on the photoisomerization of the protonated and deprotonated forms of two analogues of the photoactive yellow protein (PYP) chromophore. These are trans-p-hydroxybenzylidene acetone and trans-p-hydroxyphenyl cinnamate, studied in solutions of different polarity and viscosity at room temperature, by means of femtosecond fluorescence up-conversion. The fluorescence lifetimes of the protonated forms are found to be barely sensitive to solvent viscosity, and to increase with increasing solvent polarity. In contrast, the fluorescence decays of the deprotonated forms are significantly slowed down in viscous media and accelerated in polar solvents. These results elucidate the dramatic influence of the protonation state of the PYP chromophore analogues on their photoinduced dynamics. The viscosity and polarity effects are, respectively, interpreted in terms of different isomerization coordinates and charge redistribution in S(1). A trans-to-cis isomerization mechanism involving mainly the ethylenic double-bond torsion and/or solvation is proposed for the anionic forms, whereas "concerted" intramolecular motions are proposed for the neutral forms.     

高效液相色谱-原子荧光光谱法分析底泥孔隙水中形态砷

砷是我国实施排放总量控制的指标之一,不同形态砷的毒性差别较大,因此研究砷的形态具有重要的意义. 当前形态砷的研究主要集中在水产品方面,而对底泥孔隙水中形态砷研究较少. 底泥孔隙水中砷的形态及污染情况是重要的环境指标,可影响生活于其中的生物并间接影响人类健康. 采用高效液相色谱-原子荧光光谱法,以磷酸氢二铵为流动相,盐酸为载流,硼氢化钾为还原剂,对流动相的pH、光电倍增管负高压、空心阴极灯电流、盐酸体积分数、硼氢化钾浓度等参数进行了优化. 在优化的测试条件下,亚砷酸盐[As(Ⅲ)]、二甲基砷(DMA)、一甲基砷(MMA)和砷酸盐[As(Ⅴ)] 4种砷的形态在5~100 μg/L范围内线性关系良好,标准曲线线性相关系数均大于0.999 1,4种形态砷的检出限在0.22~0.43 μg/L之间,相对标准偏差(RSD)均小于4.0%,各组分的加标回收率在89.0%~103.0%之间. 测试结果表明方法准确可靠、操作简单,可用于底泥孔隙水中形态砷的测定.