The suppression of enhanced bitterness intensity of macrolide dry syrup mixed with an acidic powder

The aim of the present study was to identify a medicine which strongly enhanced the bitterness of clarithromycin dry syrup (CAMD) when administered concomitantly and to develop a method to suppress this enhanced bitterness. The bitterness enhancement was evaluated not only by gustatory sensation tests but also using pH and taste sensor measurements of the mixed sample. A remarkable bitterness enhancement was found when CAMD was mixed with the acidic powder L-carbocysteine. The acidic pH (pH 3.40) of the suspension made from these two preparations, seemed to be due to enhanced release of clarithromycin caused by the dissolution of the alkaline polymer film-coating. Several methods for preventing this bitterness enhancement were investigated. Neither increasing the volume of water taken with the mixture, nor changing the ratio of CAMD:L-carbocysteine in the mixture, were effective in reducing the bitterness intensity of the CAMD/L-carbocysteine mixture. The best way to achieve taste masking was to first administer CAMD mixed with chocolate jelly, which has a neutral pH, followed by the L-carbocysteine suspension. Similar results were obtained for the bitterness suppression of azithromycin fine granules with L-carbocysteine. The chocolate jelly will be useful for taste masking of bitter macrolide drug formulations, when they need to be administered together with acidic drug formulations.     

Biosurfactant production by cultivation of Bacillus atrophaeus ATCC 9372 in semidefined glucose/casein-based media

Biosurfactants are proteins with detergent, emulsifier, and antimicrobial actions that have potential application in environmental applications such as the treatment of organic pollutants and oil recovery. Bacillus atrophaeus strains are nonpathogenic and are suitable source of biosurfactants, among which is surfactin. The aim of this work is to establish a culture medium composition able to stimulate biosurfactants production by B. atrophaeus ATCC 9372. Batch cultivations were carried out in a rotary shaker at 150 rpm and 35 degrees C for 24 h on glucose-and/or casein-based semidefined culture media also containing sodium chloride, dibasic sodium phosphate, and soy flour. The addition of 14.0 g/L glucose in a culture medium containing 10.0 g/L of casein resulted in 17 times higher biosurfactant production (B(max)=635.0 mg/L). Besides, the simultaneous presence of digested casein (10.0 g/L), digested soy flour (3.0 g/L), and glucose (18.0 g/L) in the medium was responsible for a diauxic effect during cell growth. Once the diauxie started, the average biosurfactants concentration was 16.8% less than that observed before this phenomenon. The capability of B. atrophaeus strain to adapt its own metabolism to use several nutrients as energy sources and to preserve high levels of biosurfactants in the medium during the stationary phase is a promising feature for its possible application in biological treatments.     

Spectrophotometric determination of pipazethate HCl, dextromethorphan HBr and drotaverine HCl in their pharmaceutical preparations

A simple, accurate and highly sensitive spectrophotometric method is proposed for the rapid determination of pipazethate hydrochloride, dextromethorphan hydrobromide and drotaverine hydrochloride using chromotrope 2B (C2B) and chromotrope 2R (C2R). The method consists of extracting the formed ion-associates into chloroform in the case of pipazethate HCl and dextromethorphan HBr or into methylene chloride in the case of drotaverine HCl. The ion-associates exhibit absorption maxima at 528, 540 and 532 nm with C2B and at 526, 517 and 522 nm with C2R for pipazethate HCl, dextromethorphan HBr and drotaverine HCl, respectively. The calibration curves resulting from the measurements of absorbance-concentration relations (at the optimum reaction conditions) of the extracted ion-pairs are linear over the concentration range 4.36-52.32 microg mL(-1) for pipazethate, 3.7-48.15 microg mL(-1) for dextromethorphan and 4.34-60.76 microg mL(-1) for drotaverine, respectively. The effect of acidity, reagent concentration, time, solvent and stoichiometric ratio of the ion-associates were estimated. The molar absorptivity and Sandell sensitivity of the reaction products were calculated. Statistical treatment of the results reflects that the procedure is precise, accurate and easily applied for the determination of the drugs under investigation in pure form and in their pharmaceutical preparations.     

Synthesis and photocatalytic activity of rhodium-doped calcium niobate nanosheets for hydrogen production from a water/methanol system without cocatalyst loading

Rhodium-doped calcium niobate nanosheets were synthesized by exfoliating layered KCa(2)Nb(3-x)Rh(x)O(10-δ) and exhibited high photocatalytic activity for H(2) production from a water/methanol system without cocatalyst loading. The maximum H(2) production rate of the nanosheets was 165 times larger than that of the parent Rh-doped layered oxide. The quantum efficiency at 300 nm was 65%. In this system, the methanol was oxidized to formaldehyde (main product), formic acid, and carbon dioxide by holes, whereas electrons cause the reduction of water to H(2). The conductivity of the parent layered oxide was decreased by doping, which indicates the octahedral RhO(6) unit in the lattice of the nanosheet functions as an electron trap site. The RhO(6) units in the nanosheet probably also act as reaction sites for H(2) evolution.     

A specific LC/ESI-MS/MS method for determination of 25-hydroxyvitamin D3 in neonatal dried blood spots containing a potential interfering metabolite, 3-epi-25-hydroxyvitamin D3

Vitamin D deficiency in an infant is associated with a wide range of adverse health outcomes in later life. A method for the quantification of 25‐hydroxyvitamin D₃ [25(OH)D₃, the best‐established indicator of vitamin D status] in neonatal dried blood spots (DBSs) using LC/ESI‐MS/MS has been developed and validated. The method employed two steps of derivatization, a Diels–Alder reaction with 4‐phenyl‐1,2,4‐triazoline‐3,5‐dione followed by acetylation, to enhance the detectability of 25(OH)D₃ in ESI‐MS/MS and to separate 25(OH)D₃ from 3‐epi‐25‐hydroxyvitamin D₃ [3‐epi‐25(OH)D₃], a potent interfering metabolite. 25(OH)D₃ was extracted from two DBS punches (3 mm in diameter, equivalent to 5.3 μL of whole blood), purified using an Oasis HLB^® cartridge, and subjected to derivatization prior to analysis with LC/ESI‐MS/MS. 25‐Hydroxyvitamin D₄ was used as the internal standard. This method was reproducible (intra‐ and inter‐assay RSDs, <6.9%) and accurate (analytical recovery, 95.2–102.7%), and the LOQ was 3.0 ng/mL. The developed method enabled specific quantification of 25(OH)D₃ in neonatal DBSs and detection of vitamin D deficiency without interference from 3‐epi‐25(OH)D₃.     

Introduction of Adjacent Oxygen‐Functionalities in Dimethyl Heptalenedicarboxylates

The bromination of dimethyl 8‐methoxy‐1,6,10‐trimethylheptalene‐4,5‐dicarboxylate ( 6 ; Scheme 2) with N‐bromosuccinimide (NBS) in N,N‐dimethylformamide (DMF) leads in acceptable yields to the corresponding 9‐bromoheptalenedicarboxylate 10 (Table 1). Ether cleavage of 6 with chlorotrimethylsilane (Me₃SiCl)/NaI results in the formation of oxoheptalenedicarboxylate 13 in good yield (Scheme 4). The latter can be acetyloxylated to the (acetyloxy)oxoheptalenedicarboxylate 14 with Pb(OAc)₄ in benzene (Scheme 5). Oxo derivative 14 , in turn, can be selectively O‐methylated with dimethyl sulfate (DMS) in acetone to the (acetyloxy)methoxyheptalenedicarboxylates 15 and 15′ (Scheme 6). The AcO group of the latter can be transformed into a benzyl or methyl ether group by treatment with MeONa in DMF, followed by the addition of benzyl bromide or methyl iodide (cf. Scheme 9). Reduction of the ester groups of dimethyl 7,8‐dimethoxy‐5,6,10‐trimethylheptalene‐1,2‐dicarboxylate ( 25′ ) with diisobutylaluminium hydride (DIBAH) in tetrahydrofuran (THF) leads to the formation of the corresponding dimethanol 26′ , which can be cyclized oxidatively (IBX, dimethyl sulfoxide) to 8,9‐dimethoxy‐6,7,11‐trimethylheptaleno[1,2‐c]furan ( 27 ; Scheme 11).     

Novel Synthesis of Some Phthalazinone Derivatives

Dimethyl homophthalate condensed with isatin to give the unexpected five membered lactone 3 rather than the half ester 1 and the δ‐lactone 2 . Treatment of compound 3 with excess hydrazine hydrate afforded phthalazinone carbohydrazide 4 which represents a novel method for the synthesis of phthalazinone derivatives. The carbohydrazide 4 upon treatment with carbon disulphide afforded 1,3,4‐oxadiazole derivative 5 , which reacted with ethylchloroacetate to give the S‐alkylated product 6 . The structure of compound 3 compared with 2 was discussed using hyperchem professional (7) AM₁ calculations, X‐ray single crystal structure and complete spectral data.     

Effect of wood properties on within-tree variation in ultrasonic wave velocity in softwood

The radial variations in the velocity of longitudinal waves propagating through Japanese cedar and Japanese cypress were experimentally investigated. In addition, the tracheid length (TL), microfibril angle (MFA), air-dried density (AD), and moisture content (MC) were measured in order to determine the effect of wood properties on velocity variations within the wood trunk. For both species, the longitudinal wave velocities measured in the longitudinal direction (V_L) exhibited minimum values near the pith. For Japanese cedar, V_L increased from 3600 m/s toward the bark and soon attained a constant value (=4500 m/s). On the other hand, for Japanese cypress, V_L kept increasing from 4000 m/s near the pith to 4800 m/s at the bark. These radial variations in V_L coincided with those in the tracheid length. V_L exhibited strong correlations with TL and MFA with a significant level of (p < 0.01). These findings suggest that the TL and MFA greatly affect the radial variation in the ultrasonic wave velocity in softwood.     

Fabrication of a mid-IR wire-grid polarizer by direct imprinting on chalcogenide glass

A mid-IR wire-grid polarizer with a 500 nm pitch was fabricated on a low toxic chalcogenide glass (Sb-Ge-Sn-S system) by the thermal imprinting of periodic grating followed by the thermal evaporation of Al metal. After imprinting, deposition of Al on the grating at an oblique angle produced a wire-grid polarizer. The fabricated polarizer showed polarization with TM transmittance greater than 60% at 5-9 μm wavelengths and an extinction ratio greater than 20 dB at 3.5-11 μm wavelengths. This polarizer with a high extinction ratio can be fabricated more simply and less expensively than conventional IR polarizers.