Formulation variation and in vitro-in vivo correlation for a rapidly swellable three-layered tablet of tamsulosin HCl

In order to develop a preferable once-a-day oral tablet formulation, various formulations of three-layered tablets containing tamsulosin HCl as a hydrophilic model drug were evaluated and compared with a commercial reference, tamsulosin OCAS?. When the test tablet was exposed to a release medium, the medium quickly permeated to the mid-layer and the two barrier layers swelled surrounding the mid-layer rapidly. Volume expansion showed faster and enough swelling of the three-layered tablet up to 2 h. Larger amount of barrier layers caused reduced release kinetics and a high molecular weight polymer showed more resistance against agitation force. A formulation with water-soluble mid-layer showed fast erosion decreasing its volume significantly. On the pharmacokinetic study, the mean ratio of area under the curve (AUC) and C(max) for the test formulation to the reference was 0.69 and 0.84, respectively, showing that the absorption of the drug was less complete than the reference. Plasma concentration at 24 h of the test formulation was higher than the reference. The Wagner-Nelson method showed that decreased initial dissolution rate might be the cause of the less complete absorption. On considering in vitro-in vivo correlation (IVIVC), level A, the reference (R2=0.981) showed more linear relationship than the test (R2=0.918) due to the decreased dissolution and absorption rate of the formulation. This result suggests that the in vitro dissolution profiles and release kinetics might be useful in correlating absorption kinetics as well as overall plasma drug concentration-time profiles for formulation studies.     

Functionalized methanofullerenes used as n-type materials in bulk-heterojunction polymer solar cells and in field-effect transistors

The synthesis of two well-solubilized [60]methanofullerene derivatives ( p- EHO-PCBM and p- EHO-PCBA) is presented for usage in organic solar cells and in field-effect transistors. The para position of the PCBM's phenyl ring was substituted with a branched alkoxy side chain, which contributes to higher solubility, facilitating synthesis, purification, and processing. We find a small change of the open-circuit voltage ( V oc) as a slight improvement in performance upon application in P3HT/[60]methanofullerene bulk-heterojunction-photovoltaic cells, when compared to PCBM, because of the electron donation of the alkoxy group. In the case of the devices with a TiO x layer, the best power conversion efficiencies (PCE, eta e) is observed in a layered structure of P3HT/ p- EHO-PCBA/TiO x (eta e = 2.6%), which slightly exceeds that of P3HT/PCBM/TiO x (eta e = 2.3%) under conditions reported here. This can be attributed, in part, to the carboxylic acid group in p- EHO-PCBA that leads to an effective interface interaction between the active layer and TiO x phase. In addition, n-channel organic field-effect transistor (OFET) devices were fabricated with thin films of p- EHO-PCBM and p- EHO-PCBA, respectively cast from solution on SiO 2/Si substrates. The values of field-effect mobility (mu) for p- EHO-PCBM and p- EHO-PCBA are 1 x 10 (-2) and 1.6 x 10 (-3) cm (2)/V.s, respectively. The results in this paper demonstrate the effects of a carboxylic acid group and an electron-donating substituent in [60]methanofullerenes as n-type materials with respect to organic solar cells and OFET applications.     

High resolution on a quadrupole ion trap mass spectrometer

By using a modified ion trap mass spectrometer, resolution in excess of 30,000 (FWHM) at m I z 502 is demonstrated. The method of increasing resolution in the ion trap mass spectrometer operated in the mass-selective instability mode depends on decreasing the rate of scanning the primary radio frequency amplitude as well as using resonance ejection at the appropriate frequency and amplitude. A theoretical basis for the method is introduced.     

Analysis of the spin lattice model for the spin-gapped layered compounds Na(3)Cu(2)SbO(6) and Na(2)Cu(2)TeO(6) on the basis of electronic structure calculations

The spin lattice model for the spin-gapped layered magnetic solids Na3Cu2SbO6 and Na2Cu2TeO6 was examined by evaluating the three spin exchange interactions of their Cu2MO6 (M = Sb, Te) layers in terms of spin dimer analysis based on extended Hückel tight binding calculations and mapping analysis based on first principles density functional theory electronic band structure calculations. For both compounds, our calculations show that the two strongest spin exchange interactions, that is, the Cu-O...O-Cu super-superexchange (J2) and the Cu-O-Cu superexchange (J1) interactions, form alternating chains that interact weakly through the Cu-O-Cu superexchange (J3) interactions. The dominant one of the three spin exchange interactions is J2, and it is antiferromagnetic in agreement with the fact that both of the compounds are spin gapped. For Na3Cu2SbO6 and Na2Cu2TeO6, the superexchange J1 is calculated to be ferromagnetic, hence, leading to the alternating chain model in which antiferromagnetic and ferromagnetic spin exchange interactions alternate. This picture does not agree with the recent experimental analysis, which showed that the temperature-dependent magnetic susceptibilities of both compounds should be described by the alternating chain model in which two antiferromagnetic spin exchange interactions of different strengths alternate.     

Rate constants for the etching of gallium arsenide by atomic chlorine

Known chlorine atom concentrations were prepared in a discharge flow system and used to etch the (100) face of a gallium arsenide single crystal. The etch rate was monitored by mass spectrometry, laser interferometry, and surface proftlometry. In the temperature range from 90 to 160°C the reaction can be described by the rate law $$Etch rate = kP_{Cl} $$ where $$k = 9 \times 10^{(6 \pm 0.5)} \mu m min^{ - 1} Torr^{ - 1} e^{ - 9 \pm 1)kcal/RT} $$      

Methionine synthase reductase polymorphisms are associated with serum osteocalcin levels in postmenopausal women

Homocysteine (Hcy) is thought to play an important role in the development of osteoporosis and fracture. Methionine synthase reductase (MTRR) is an enzyme involved in the conversion of Hcy to methionine. We hypothesized that certain genetic polymorphisms of MTRR leading to reduced enzyme activity may cause hyperhomocysteinemia and affect bone metabolism. We therefore examined the associations of the A66G and C524T polymorphisms of the MTRR gene with bone mineral density (BMD) and serum osteocalcin levels in postmenopausal women. Although we did not detect any significant associations between MTRR polymorphisms and BMD or serum osteocalcin levels, we found that the 66G/524C haplotype, which has reduced enzyme activity, was significantly associated with serum osteocalcin levels in a gene-dose dependent manner (P = 0.002). That is, the highest osteocalcin levels (34.5 +/- 16.8 ng/ml) were observed in subjects bearing two copies, intermediate osteocalcin levels (32.6 +/- 14.4 ng/ml) were observed in subjects bearing one copy, and the lowest levels of osteocalcin (28.8 +/- 10.9 ng/ml) were observed in subjects bearing no copies. These results suggest that the 66G/524C haplotype of the MTRR gene affect bone turn over rate.     

Application and exploration of fast gas chromatography-surface acoustic wave sensor to the analysis of thymus species

Fast gas chromatography combined with surface acoustic wave sensor (GC/SAW) has been applied for the detection of volatile aroma compounds emanated from thymus medicinal plants such as T. quinquecostotus (Jeju and Mt. Gaya in South Korea), T. quinquecostotus var. japonica (Ulreung island in South Korea), T. mongolicus (Northeastern Asia), and T. serpyllum (Europe). The GC/SAW involving the fragrance pattern analysis provides a novel analytical method with a very fast separation and characterization of aromas caused by the delicate difference of chemical composition according to botanical and geographical origin. On the comparison of experiments, the characteristic components and analytical tendency for air-dried thymus species detected by GC/SAW appear to be quite similar to those obtained by headspace solid-phase microextraction (HS-SPME)-GC-MS, but the abundance ratios between these two methods are different. In addition to that, the discrimination of various thymus species by using VaporPrint image based on GC/SAW provides a quite reliable result. On the basis of principal component analysis (PCA) results, the ability for classification among species of completely different chemotypes by HS-SPME-GC-MS is good enough, but the classification of same chemotypes species which are from different geographical origin in same country, original species and its variety, an air-drying term for 13 days and 16 months appear much lower than GC/SAW. Interestingly, the present experiment reveals that the air-drying term influences the aroma composition: the concentration of the pharmacologically active species, monoterpene phenol (thymol), reaches its highest concentrations after it was dried for 5 days or 13 days, which is much higher than in fresh or over-dried for a long times.     

A degradable hyperbranched poly(ester amine) based on poloxamer diacrylate and polyethylenimine as a gene carrier

Polyethylenimine (PEI) is a well-known cationic polymer which has high transfection efficiency due to its buffering effect. However, nondegradability, cytotoxicity, aggregation, and short-circulation time in vivo still need to be overcome for a successful gene delivery. Degradable, hyperbranched poly(ester amine)s (PEAs) based on poloxamer diacrylate and low molecular weight branched PEI, were successfully synthesized and evaluated as a nonviral gene carrier. The PEAs were obtained in significant yields through Michael type addition reaction of diacrylate monomers and low molecular weight branched PEI. Analysis of degradation products by the reduction in molecular weight demonstrated that PEAs degrade in a controlled fashion. The PEA showed good DNA binding ability and the sizes of complexes under physiological condition were below 150 nm, implicating its potential for intracellular delivery. It showed lower cytotoxicity in three different cell lines (A549, 293T, and HepG2) compared with PEI 25K. PEAs showed much higher transfection efficiencies in three cell lines compared with PEI 25K and PEI 1.8K, and revealed little serum dependency in A549 cell line when the content of poloxamer in the PEA was increased up to 30%.     

Massively parallel concentration device for multiplexed immunoassays

A massively parallel nanofluidic concentration device array for multiplexed and high-throughput biomolecule detection is demonstrated. By optimizing the microchannel/nanojunction design and channel conductivity, an array of up to 128 nanofluidic concentration devices were fabricated. Operation of the entire array requires only one inlet and one outlet reservoir, with the application of a single operational voltage bias across them. Concentration efficiencies of the devices were found to be uniform within the array, within 5% error. Alternatively, concentration speed in each channel can be individually tuned by controlling the length of the inlet microchannel and thus controlling the flow rate based on change of the tangential electric field. This allows immuno-binding reactions at different concentration ranges to be performed in parallel. Using multiplexed, successive-concentration enhanced detection in the device, we have shown that the dynamic range and reliability of the immunoassay can be significantly increased.     

The kinetics of competing multiple-barrier unimolecular dissociations of o-, m-, and p-chlorotoluene radical cations

The kinetics of competing multiple-barrier unimolecular dissociations of o-, m-, and p-chlorotoluene radical cations to C7H7(+) (benzyl and tropylium) are studied by ab initio/Rice-Ramsperger-Kassel-Marcus (RRKM) calculations. This system presents a very intriguing kinetic example in which the conventional approach assuming a single-barrier or a double-well potential surface with one transition state cannot predict or explain the outcome. The molecular parameters obtained at the SCF level of theory with the DZP basis set are utilized for the evaluation of microcanonical RRKM rate constants with no adjustable parameters. First-principles calculations provide the microscopic details of the reaction kinetics along the two competing multiple-barrier reaction pathways: the rate-energy curves for all elementary steps; temporal variations of the reactants, the reaction intermediates, and the products; and the product yield as a function of energy. The rate constant for each channel is calculated as a function of the internal energy at 0 K. After the thermal correction, the calculated rate-energy curves for the benzyl channel agree well with the photoelectron photoion coincidence data obtained at room temperature for all three isomers. Close agreement between experiments and theory suggests that first-principles calculations taking the full sequence of kinetic steps into account offer a useful kinetic model capable of correctly predicting the outcome of competing multiple-barrier reactions. The slowest process is identified as [1,2] and [1,3] alpha-H migration at the entrance to the tropylium and benzyl channel, respectively. However, the overall rate is determined not by the slowest process, but by the combination of the slowest rate and the net flux toward the product, which is multiplicatively reduced with an increasing number of reaction intermediates. The product yield calculation confirms the benzyl cation as the predominant product. For all isomers, the thermodynamically most stable tropylium ion is produced much less than expected because a large fraction of flux coming into the tropylium channel goes back to the benzyl channel. The benzyl channel is kinetically favored because it involves a lower entrance barrier with fewer rearrangements than the tropylium channel.