Simultaneous determination of olmesartan medoxomil and irbesartan and hydrochlorothiazide in pharmaceutical formulations and human serum using high performance liquid chromatography

 A simple, selective, sensitive, precise, simultaneous high performance liquid chromatographic analysis of serum samples and commercial tablet formulation containing hydrochlorothiazide, olmesartan medoxomil and irbesartan are reported. Good chromatographic separation was achieved using a μ-Bondapak, C18 column (15 cm×4.6 mm, 5 μm), and a mobile phase consisting of acetonitrile-0.2% acetic acid aqueous solution (50∶50, v/v) at a flow rate of 1.0 mL/min. The ultraviolet detector was set at a wavelength of 260 nm. Hydrochlorothiazide, olmesartan medoxomil, and irbesartan were eluted at 1.2, 3.8, and 4.4 min, respectively. No extraneous materials were found to interfere. The method uses protein precipitation with acetonitrile for the preparation of serum sample. The linear ranges for hydrochlorothiazide, olmesartan medoxomil, and irbesartan were 6.25-18.75, 20-60, and 75-225 ng/mL, respectively. The recoveries of hydrochlorothiazide, olmesartan medoxomil, and irbesartan in spiked samples were all greater than 98%, and their relative standard deviations were less than 2.0%. The limits of detection were 1, 2, and 2 ng/mL for hydrochlorothiazide, olmesartan medoxomil, and irbesartan, respectively, and the limits of quantification were 3 ng/mL, which allow their determination at the expected serum concentration levels.     

Novel variational formulations for nonlocal plasticity

A nonlocal structural model of softening plasticity is considered in the framework of the internal variable theories of inelastic behaviours of associative type. The finite-step nonlocal structural problem in a geometrically linear range is formulated according to a backward difference scheme for time integration of the flow rule. The related finite-step variational formulation in the complete set of local and nonlocal state variables is recovered. A family of mixed nonlocal variational formulations, with different combinations of state variables, is provided starting from the general variational formulation. The specialization of a mixed variational formulation to existing nonlocal models of softening plasticity, assuming both linear and nonlinear constitutive behaviour, is provided to show the effectiveness of the theory.     

Colorimetric Estimation of Melatonin in Pharmaceutical Formulations

 Three simple and sensitive colorimetric methods (A–C) for the determination of melatonin in bulk samples and in pharmaceutical formulations are described. They are based on the formation of coloured species by reaction of ninhydrin with the drug (method A, λ_max 397 nm) by oxidation of the indol moiety in melatonin with potassium persulphate (method B, λ_max 450 nm) or by reduction of osmium (VIII) (method C, λ_max 516 nm). Regression analysis of Beer-Lambert plots showed good correlations in concentration ranges between 0.8–14.2, 70.0–140.0 and 2.0–40.0 μg/mL for methods A, B and C, respectively. The molar absorptivity, Sandell sensitivity and detection limit were calculated. For more accurate analysis, Ringbom optimum concentration ranges were calculated. The validity of the proposed methods was tested by analysing pharmaceutical formulations containing melatonin. The relative standard deviations were ≤ 0.95% with recoveries 99.0–101.33%. Received October 20, 1999. Revision February 10, 1999.     

Nonlocal and gradient rate plasticity

This paper deals with a formulation of nonlocal and gradient plasticity with internal variables. The constitutive model complies with local internal variables which govern kinematic hardening and isotropic softening and with a nonlocal corrective internal variable defined either as the sum between a new internal variable and its spatial weighted average or as the gradient of a measure of plastic strain. The rate constitutive problem is cast in the framework provided by the convex analysis and the potential theory for monotone multivalued operators which provide the suitable tools to perform a theoretical analysis of such nonlocal and gradient problems. The validity of the maximum dissipation theorem is assessed and constitutive variational formulations of the rate model are provided. The structural rate problem for an assigned load rate is then formulated. The related variational formulation in the complete set of state variable is contributed and the methodology to derive variational formulations, with different combinations of the state variables, is explicitly provided. In particular the generalization to the present nonlocal and gradient model of the principles of Prager–Hodge, Greenberg and Capurso–Maier is presented. Finally nonlocal variational formulations provided in the literature are derived as special cases of the proposed model.     

Theory of electroelasticity accounting for biasing fields: Retrospect,comparison and perspective

力电耦合固体的非线性连续介质理论最早出现于20世纪50年代,而成熟于70年代.80年代末、90年代初则因智能材料与结构的兴起而又得到了新的发展,引起了较为广泛的关注,但应用上以线性分析为主.21世纪初以来,力电耦合软材料因其潜在的应用前景激发了众多的研究兴趣.由于牵涉到大变形,必须在一般非线性连续介质力学的框架内进行问题的建模和开展定量分析,因此力电耦合固体的非线性理论重新得到了大家的重视,出现了很多新版本.本文旨在阐述力电耦合固体非线性连续介质理论一般框架的基础上,采用3个构型的表述方式,较为详细地给出拉格朗日描述和更新拉格朗日描述下的力电耦合偏场理论,甄别不同理论表述版本之间的异同,以廓清目前文献中的混乱现象,为今后的相关研究提供理论指导.最后,本文讨论和展望了力电耦合偏场理论在不同研究领域的若干研究重点及其未来发展趋势.     

A Note on “Lot-sizing with fixed charges on stocks: The convex hull”

We update and complete the proof of Proposition 7 in Van Vyve and Ortega (2004) [1], which states that the projection of a facility location reformulation of an uncapacitated lot-sizing problem with fixed charges on stocks (ULSW) to the original space is equivalent to that of the tight shortest path reformulation of ULSW. Their proof is interesting and consists of two cases, only first of which is analyzed in detail. We show that the second case exhibits several challenges not present in the first one and necessitates an updated proof.     

A Novel Strategy for Quantifying Clopidogrel Using Square‐wave Voltammetry and a Boron‐doped Diamond Film

The voltammetric behavior of clopidogrel bisulfate (CLO), an antiplatelet agent, was investigated for the first time in the literature on a cathodically pretreated boron‐doped diamond electrode (CP‐BDDE) using cyclic (CV) and square‐wave voltammetry (SWV). It was observed an anodic peak for CLO, suitable for analytical purposes, at about 1.15 V (vs. Ag/AgCl (3.0 mol L^?1 KCl)) by CV in Britton‐Robinson buffer solution (pH 5.0). On the physical‐chemical characterization of the interface phenomena, it was proved that electrode reaction of the analyte was controlled by a diffusion process. At optimized square‐wave parameters (pulse amplitude of 60 mV, frequency of 30 Hz and scan increment of 3 mV), the obtained analytical curve was linear for the CLO concentration range from 0.60 to 60.0 μmol L^?1, with a detection limit of 0.60 μmol L^?1. The simple, rapid and greener analytical method, based on CP‐BDDE electrochemical sensor, was successfully applied in real samples (pharmaceuticals and urine).     

Nano‐in‐Micro POxylated Polyurea Dendrimers and Chitosan Dry Powder Formulations for Pulmonary Delivery

Pulmonary administration offers excellent advantages over conventional drug delivery routes, including increasing therapeutics bioavailability, and avoiding long‐term safety issues. Formulations of nano‐in‐micro dry powders for lung delivery are engineered using (S)‐ibuprofen as a model drug. These biodegradable formulations comprise nanoparticles of drug‐loaded POxylated polyurea dendrimers coated with chitosan using supercritical‐fluid‐assisted spray drying. The formulations are characterized in terms of morphology, particle‐size distribution, in vitro aerodynamic particle pulmonary distribution, and glutathione‐S‐transferase assay. It is demonstrated that ibuprofen‐loaded nanoparticles can be successfully incorporated into microspheres with adequate aerodynamic properties, mass median aerodynamic diameter (1.86–3.83 μm), and fine particle fraction (28%–45%), for deposition into the deep lung. The (S)‐ibuprofen dry powder formulations show enhanced solubility, high swelling behavior and a sustained drug release at physiologic pH. Also, POxylated polyureas decrease the (S)‐ibuprofen toxic effect on cancer cellular growth. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS) assays show no significant cytotoxicity on the metabolic activity of human lung adenocarcinoma ephithelial (A549) cell line for the lowest concentration (1 × 10^?3 m ), even for longer periods of contact with the cells (up to 120 h), and in the normal human dermal fibroblasts cell line the toxic effect is also reduced.     

Urea as new stabilizing agent for imipenem determination: electrochemical study and determination of imipenem and its primary metabolite in human urine

Imipenem shows a fast chemical conversion to a more stable imin form (identical to that of biochemical dehydropeptidase degradation) in aqueous solutions and stabilizing agents used avoid its electrochemical study and determination.The aim of this work is the proposal of urea as stabilizing agent which allows the electrochemical study of imipenem and the proposal of electrochemical methods for the determination of imipenem and its primary metabolite (M1) in human urine samples. Electrochemical studies were realized in phosphate buffer solutions over pH range 1.5-8.0 using differential-pulse polarography, DC-tast polarography, cyclic voltammetry and adsorptive stripping voltammetry. In acidic media, a non-reversible diffusion-controlled reduction involving a two steps mechanism which involves one electron and one proton in the first step and two electrons and two protons in the second step occurs and the mechanism for the reduction was suggested.A differential-pulse polarographic method for the determination of imipenem in the concentration range 3.2 × 10⁻⁶ to 2 × 10⁻⁵ M (0.95-3.4 mg/L) and its primary metabolite in the concentration range 1.4 × 10⁻⁶ to 10⁻⁴ M (0.43-26.1 mg/L) with detection limits of 9.6 × 10⁻⁷ M (0.28 μg/L imipenem) and 4.3 × 10⁻⁷ M (0.14 μg/L M1) was proposed. Also, a method based on controlled adsorptive pre-concentration of imipenem on the hanging mercury drop electrode followed by voltammetric measure, allows imipenem determination in the concentration range 1.8 × 10⁻⁸ to 1.2 × 10⁻⁶ M (5.42-347 μg/L) with a detection limit of 5.4 × 10⁻⁹ M (1.63 μg/L). The proposed methods have been used for the direct determination of the analytes in a pharmaceutical formulation and human urine.     

Pectin-Based Formulations for Controlled Release of an Ellagic Acid Salt with High Solubility Profile in Physiological Media

Among bioactive phytochemicals, ellagic acid (EA) is one of the most controversial because its high antioxidant and cancer-preventing effects are strongly inhibited by low gastrointestinal absorption and rapid excretion. Strategies toward an increase of solubility in water and bioavailability, while preserving its structural integrity and warranting its controlled release at the physiological targets, are therefore largely pursued. In this work, EA lysine salt at 1:4 molar ratio (EALYS), exhibiting a more than 400 times increase of water solubility with respect to literature reports, was incorporated at 10% in low methoxylated (LM) and high methoxylated (HM) pectin films. The release of EA in PBS at pH 7.4 from both film preparations was comparable and reached 15% of the loaded compound over 2 h. Under simulated gastric conditions, release of EA from HM and LM pectin films was minimal at gastric pH, whereas higher concentrations—up to 300 μM, corresponding to ca. 50% of the overall content—were obtained in the case of the HM pectin film after 2 h incubation at the slightly alkaline pH of small intestine environment, with the enzyme and bile salt components enhancing the release. EALYS pectin films showed a good prebiotic activity as evaluated by determination of short chain fatty acids (SCFAs) levels following microbial fermentation, with a low but significant increase of the effects produced by the pectins themselves. Overall, these results highlight pectin films loaded with EALYS salt as a promising formulation to improve administration and controlled release of the compound.