Scale-up of high shear granulation based on agitation power

Scale-up of wet granulation in a vertical high shear mixer was conducted. Pharmaceutical excipient mixtures composed of lactose, cornstarch and micro-crystalline cellulose, and hydroxypropylecellulose as a binder were mixed together and then granulated with purified water under various operating conditions and vessel scales. Torque of agitator shaft was continuously measured and then agitation power per unit vessel volume was calculated. The agitation power per unit vessel volume showed a good correlation with physical properties of obtained granules, such as mass median diameter, strength and compressibility. This implied that the scale-up characteristics could be well analyzed by means of the agitation power per unit vessel volume. In addition, the effects of agitator tip speed and Froude number on the agitation power per unit vessel volume were investigated. The results showed that the agitation power per unit vessel volume was well characterized by the tip speed rather than the Froude number. This meant that the granule growth mainly progressed by the shear stress from the agitator blade. Dynamic characteristics of high shear granulation were also discussed here.     

The structure of ancovenin,a new peptide inhibitor of angiotensin I converting enzyme

The structure of ancovenin, a new peptide inhibitor of angiotensin I converting enzyme, was determined to be a unique tricyclic peptide which comprises sixteen amino acid residues including dehydroalanine and three sulfide amino acids as unusual components.     

Ionic polymerization under an electric field. III. Cationic polymerizations of α-methylstyrene and styrene

Cationic polymerizations of α-methylstyrene and styrene were carried out in an electric field with iodine as a catalyst and ethylene dichloride as the solvent. The effects of the field on the rate of polymerization and the degree of polymerization were studied. It was found that the field increased the rate of polymerization of α-methylstyrene and, also slightly increased the degree of polymerization, whereas the field had no influence on these quantities in the case of styrene. The expressions for the rate of polymerization and the degree of polymerization, which were derived in a previous paper and refined in the present paper, show that these quantities are generally a function of the degree of dissociation of ion pairs at growing chain ends. For a comparatively large degree of dissociation, these expressions can account for the field effect as was observed on α-methylstyrene, if one assumes that the degree of dissociation in the presence of an electric field is larger than that in its absence, and that the free-ion propagation proceeds much faster than the ion-pair propagation. For a small degree of dissociation, however, these expressions become practically independent of the degree of dissociation so that a possible increase due to the presence of an electric field gives rise to no observable effect on the polymerization. This situation may be interpreted as corresponding to the case of styrene. In other words, the polymerization of α-methylstyrene has more free ionic character than that of styrene.     

DNA separation by microchip electrophoresis using low-viscosity hydroxypropylmethylcellulose-50 solutions enhanced by polyhydroxy compounds

Low-viscosity polymer solutions have potential for double-stranded (ds) DNA separations in micrototal analysis systems (micro-TAS). In this paper, we report dilute, low-viscosity hydroxypropylmethylcellulose-50 (HPMC-50, 11.5 kDa) solutions containing polyhydroxy additives as separation media. Predominant operational variables, such as applied electric field strength, fluorescent intercalator (YOPro-1) concentration, polymer concentration, and additive concentration, are thoroughly investigated. Fast (within 170 s) and excellent separation of DNA restriction fragments ranging in size from 72 to 1353 base pairs (bp) is achieved in a 30 mm length channel of polymethylmethacrylate (PMMA) microchips at an electric field strength of 300 V/cm, by introducing 8% mannitol, 8% glucose or 10% glycerol additives into a 2% HPMC-50/1 x Tris-borate-EDTA (TBE) solution. The low-viscosity (40 cP) matrix formulation provides both coating of the microchannels and separation of DNA in one step. The performance in the solution surpasses that in highly concentrated HPMC-50 solution. In addition, separation using 1xTris-EDTA buffer in the 2% HPMC-50 matrix containing polyhydroxy additives also exhibits a notably increased performance. This is presumably due to formation of hydrogen-bonding interactions of polyhydroxy additives with HPMC-50 matrix and DNA so as to increase the coupling interactions between matrix and DNA molecules during electrophoresis. The result reflects that boric acid is not a prerequisite in polyhydroxy-enhanced HPMC-50 solution for separation.     

Thermolysis of [1,2,4]triazolo[1,5-a]pyrimidine n-ylides

5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidinio-3-phenacylide ($\text{3}$) generated by the reaction of an iminium salt ($\text{2}$) with 1 eq. of triethylamine, underwent a new thermal ring cleavage of the triazole moiety to give the pyrimidine derivative. However reaction of $\text{2}$ with 2 eq. of triethylamine afforded the 2-iminooxazoline derivative. The iminooxazoline reacted with nucleophiles such as alcohols or amines to give imidazoles.     

Precursor mediated cycloaddition reaction of ethylene to the Si(100)c(4 x 2) surface

We report the direct observation of a precursor state for the cycloaddition reaction (the di-sigma bond formation) of ethylene on Si(100)c(4 x 2) using high-resolution electron energy loss spectroscopy at low temperature, and the meta-stable precursor state is identified as a weakly bonded pi-complex type. The activation energy from the pi-complex precursor to the di-sigma bonded species is experimentally estimated to be 0.2 eV. First-principles calculations support the pi-complex precursor mediated cycloaddition reaction of ethylene on Si(100)c(4 x 2).     

A new RNA synthetic method with a 2'-O-(2-cyanoethoxymethyl) protecting group

A novel method for the synthesis of RNA oligomers with 2-cyanoethoxymethyl (CEM) as the 2'-hydroxyl protecting group has been developed. The new method allows the synthesis of oligoribonucleotides with an efficiency and final purity comparable to that obtained in DNA synthesis. [structure: see text]     

Facile synthesis of 6a-carbaprostaglandin i2

The optically active 6a-carbaprostaglandin I₂ (2), a stable mimic of natural prostacylin (1), was synthesized from the lactone 4 or the hydroxy acid 5, which were general synthetic intermediates for natural prostaglandins.     

Analysis of DNA polymorphisms on the human Y-chromosome by microchip electrophoresis

Validation of microchip electrophoresis in DNA analysis has been carried out using an Agilent 2100 Bioanalyzer. With a DNA 500 Assay Kit, the reproducibility and accuracy of fragment sizing of a 10 bp DNA ladder have been shown to be satisfactory with the relative standard deviation and the relative error mostly below 1.0 and 5.0% (n = 12), respectively. Both intraday and interday validations of fragment sizing and quantitation have also been performed with a 7500 Assay Kit (n = 48). Although the results of quantitation are not as good as that of sizing, due to the manual introduction of samples and markers into the chip wells, they are still sufficient to carry out further analyses of practical samples. Based on such reliable results, fast analysis of DNA polymorphisms on the human Y-chromosome has been realized with microchip electrophoresis. The total analysis times of three genomic polymorphisms on the Y-chromosome, Y Alu polymorphism, 47z/StuI, and 12f2, are all within 100 s, and the relative standard deviation and relative error of fragment sizes are below 3.5 and 3.7%, respectively. In addition, a mixture of nine DNA markers on the human Y-chromosome related to examine the cause of spermatogenic failure have been separated successfully with the smallest fragment size difference of 7 bp. Our results demonstrate the potential of microchip electrophoresis in polymorphism analysis with the advantages of high speed, good reproducibility, high precision, and high resolution.     

Vectorial electron relay at ITO electrodes modified with self-assembled monolayers of ferrocene-porphyrin-fullerene triads and porphyrin-fullerene Dyads for molecular photovoltaic devices

Systematic series of indium tin oxide (ITO) electrodes modified covalently with self-assembled monolayers (SAMs) of ferrocene-porphyrin-fullerene triads and porphyrin-fullerene dyads were designed to gain valuable insight into the development of molecular photovoltaic devices. The structures of SAMs on ITO have been investigated by UV/Vis absorption spectroscopy, atomic force microscopy, and cyclic voltammetry. The photoelectrochemical and photophysical (fluorescence lifetime and time-resolved transient absorption) properties were also determined. The highest quantum yield of photocurrent generation (11 %) among donor-acceptor linked systems which are covalently attached to the surface of ITO electrodes was achieved with SAMs of ferrocene-zinc porphyrin-fullerene linked triad on ITO electrodes. The quantum yields of photocurrent generation correlate well with the charge-separation efficiency and the lifetime of the charge-separated state of the porphyrin-fullerene linked systems in solution. These results provide valuable information for the construction of photonic molecular devices and artificial photosynthetic systems on ITO electrodes.