Solubility and Stability of Some Pharmaceuticals in Natural Deep Eutectic Solvents-Based Formulations

Some medicines are poorly soluble in water. For tube feeding and parenteral administration, liquid formulations are required. The discovery of natural deep eutectic solvents (NADES) opened the way to potential applications for liquid drug formulations. NADES consists of a mixture of two or more simple natural products such as sugars, amino acids, organic acids, choline/betaine, and poly-alcohols in certain molar ratios. A series of NADES with a water content of 0–30% (w/w) was screened for the ability to solubilize (in a stable way) some poorly water-soluble pharmaceuticals at a concentration of 5 mg/mL. The results showed that NADES selectively dissolved the tested drugs. Some mixtures of choline-based NADES, acid-neutral or sugars-based NADES could dissolve chloral hydrate (dissociated in water), ranitidine·HCl (polymorphism), and methylphenidate (water insoluble), at a concentration of up to 250 mg/mL, the highest concentration tested. Whereas a mixture of lactic-acid–propyleneglycol could dissolve spironolacton and trimethoprim at a concentration up to 50 and 100 mg/mL, respectively. The results showed that NADES are promising solvents for formulation of poorly water-soluble medicines for the development of parenteral and tube feeding administration of non-water-soluble medicines. The chemical stability and bioavailability of these drug in NADES needs further studies.     

On the Rational Drug Design for Hypertension through NMR Spectroscopy

Antagonists of the AT1receptor (AT1R) are beneficial molecules that can prevent the peptide hormone angiotensin II from binding and activating the specific receptor causing hypertension in pathological states. This review article summarizes the multifaced applications of solid and liquid state high resolution nuclear magnetic resonance (NMR) spectroscopy in antihypertensive commercial drugs that act as AT1R antagonists. The 3D architecture of these compounds is explored through 2D NOESY spectroscopy and their interactions with micelles and lipid bilayers are described using solid state ¹³CP/MAS, ³¹P and ²H static solid state NMR spectroscopy. Due to their hydrophobic character, AT1R antagonists do not exert their optimum profile on the AT1R. Therefore, various vehicles are explored so as to effectively deliver these molecules to the site of action and to enhance their pharmaceutical efficacy. Cyclodextrins and polymers comprise successful examples of effective drug delivery vehicles, widely used for the delivery of hydrophobic drugs to the active site of the receptor. High resolution NMR spectroscopy provides valuable information on the physical-chemical forces that govern these drug:vehicle interactions, knowledge required to get a deeper understanding on the stability of the formed complexes and therefore the appropriateness and usefulness of the drug delivery system. In addition, it provides valuable information on the rational design towards the synthesis of more stable and efficient drug formulations.     

Phytochemical and Biological Evaluation of a Newly Designed Nutraceutical Self-Nanoemulsifying Self-Nanosuspension for Protection and Treatment of Cisplatin Induced Testicular Toxicity in Male Rats

The incorporation of cisplatin (CP) as a cytotoxic antineoplastic agent in most chemotherapeutic protocols is a challenge due to its toxic effect on testicular tissues. Natural compounds present a promising trend in research, so a new nutraceutical formulation (NCF) was designed to diminish CP spermatotoxicity. A combination of three nutraceutical materials, 250 mg Spirulina platensis powder (SP), 25 mg Tribulus terrestris L. extract (TT), and 100 mg fish oil (FO) were formulated in self-nanoemulsifying self-nanosuspension (SNESNS). SP was loaded into the optimized self-nanoemulsifying system (30% FO, 50% span 80/cremophor EL and 20% isopropanol) and mixed with TT aqueous solution to form SNESNS. For the SP, phytochemical profiling revealed the presence of valuable amounts of fatty acids (FAs), amino acids, flavonoids, polyphenols, vitamins, and minerals. Transmission electron microscopy (TEM) and particle size analysis confirmed the formation of nanoemulsion-based nanosuspension upon dilution. Method validation of the phytochemical constituents in NCF has been developed. Furthermore, NCF was biologically evaluated on male Wistar rats and revealed the improvement of spermatozoa, histopathological features, and biochemical markers over the CP and each ingredient group. Our findings suggest the potential of NCF with SNESNS as a delivery system against CP-induced testicular toxicity in male rats.     

两种发电机励磁系统远程监测与控制方法研究

同步发电机励磁控制系统的监控是保证发电机良好运行的重要部分,远程监控技术能够有效的对发电机励磁控制系统进行监控,并为励磁控制系统维护人员提供方便.因此针对同步发电机励磁控制系统的典型监测和控制功能,给出了两种发电机励磁系统远程监控方法,首先基于AJAX技术,给出了一种基于web的励磁控制系统远程监测方法,所设计的监测系统能够在局域网或internet网络环境下,使用计算机或智能手机的浏览器进行励磁控制系统的监测,实际测试表明该方法是可行的.之后,为能实现励磁控制系统的远程实时控制,并解决internet网络环境下实时数据传输不稳定的情况,给出了一种基于TCP/IP和VPN技术的励磁控制系统远程监控方法,测试表明该方法能够实现励磁控制系统的实时监测和控制.     

NUMERICAL SIMULATION OF THREE-DIMENSIONAL INCOMPRESSIBLE FLOW BY A NEW FORMULATION

A new mathematical formulation, called the pseudovorticity–velocity formulation, of the three-dimensional incompressible Navier–Stokes equations is presented as an alternative to the vorticity–velocity approach. For the model lid-driven cavity flow problem in two and three dimensions, combined with an explicit mixed spectral /finite different numerical scheme the proposed formulation is found to be efficient and very accurate as compared with the results available in the literature. In particular, the simulation results demonstrate an attractive feature of the present formulation compared with the vorticity–velocity approach, namely that the divergence-free condition of the velocity field can always be achieved on a non-staggered mesh.     

AN ADAPTIVE UNSTRUCTURED TRI-TREE ITERATIVE SOLVER FOR MIXED FINITE ELEMENT FORMULATION OF THE STOKES EQUATIONS

An iterative adaptive equation solver for solving the implicit Stokes equations simultaneously with tri-tree grid generation is developed. The tri-tree grid generator builds a hierarchical grid structure which is mapped to a finite element grid at each hierarchical level. For each hierarchical finite element grid the Stokes equations are solved. The approximate solution at each level is projected onto the next finer grid and used as a start vector for the iterative equation solver at the finer level. When the finest grid is reached, the equation solver is iterated until a tolerated solution is reached. In order to reduce the overall work, the element matrices are integrated analytically beforehand. The efficiency and behaviour of the present adaptive method are compared with those of the previously developed iterative equation solver which is preconditioned by incomplete LU factorization with coupled node fill-in. The efficiency of the incomplete coupled node fill-in preconditioner is shown to be largely dependent on the global node numbering. The preconditioner is therefore tested for the natural node ordering of the tri-tree grid generator and for different ways of sorting the nodes.     

A VORTICITY–STREAMFUNCTION FORMULATION FOR STEADY INCOMPRESSIBLE TWO-DIMENSIONAL FLOWS

A vorticity–streamfunction formulation for incompressible planar viscous flows is presented. The standard kinematic field equations are discretized using centred finite difference schemes and solved in a coupled way via a Newton-like linearization scheme. The linearized system of partial differential equations is handled through the restarting linear GMRES algorithm, preconditioned by means of an incomplete LU approximate factorization. The proposed solution technique constitutes a fast and robust algorithm for treating laminar flows at high Reynolds numbers. The pressure field is obtained at a subsequent step by solving a convection– diffusion equation in terms of the stagnation pressure, which presents certain advantages compared with the widely used static pressure Poisson equation. Results are shown for a wide variety of applications including internal and external flows.     

The Effects of Formulation on Imidacloprid Dissipation in Grapes and Vine Leaves and on Required Pre-Harvest Intervals under Lebanese Climatic Conditions

In this study, imidacloprid, a systemic insecticide, currently having a specified European Commission MRL value for vine leaves (2 mg kg⁻¹), was applied on a Lebanese vineyard under different commercial formulations: as a soluble liquid (SL) and water dispersible granules (WDG). In Lebanon, many commercial formulations of imidacloprid are subject to the same critical good agricultural practice (cGAP). It was, therefore, important to verify the variability in dissipation patterns according to matrix nature and formulation type. Random samplings of grapes and vine leaves were performed starting at 2 days until 18 days after treatment. Residue extractions were performed according to the QuEChERS method and the analytical determination using liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS). The SL formulation yielded significantly higher initial deposit than the WDG formulation on grapes and vine leaves. The formulation type did not significantly affect the dissipation rates; the estimated half-lives in grapes and vine leaves were 0.5 days for all imidacloprid formulations. No pre-harvest intervals were necessary on grapes. PHIs of 3.7 days for the SL formulation and 2.8 days for the WDG formulation were estimated on vine leaves. The results showed that the type of formulation and the morphological and physiological characteristics of the matrix had an effect on the initial deposits, and thus residue levels, but not on the dissipation patterns.     

Vorticity-streamfunction formulation of unsteady incompressible flow past a cylinder: Sensitivity of the computed flow field to the location of the outflow boundary

The influence of the location of the outflow computational boundary on the unsteady incompressible flow past a circular cylinder at Reynolds number 100 is examined. The vorticity-streamfunction formulation of the Navier-Stokes equations is used in all computations. Two types of outflow boundary conditions are subjected to a series of tests in which the domain length is gradually reduced. The traction-free condition performs well in most cases and allows the outflow boundary to be located as close as 6.5 cylinder diameters from the body. The other boundary condition type is not as forgiving, but has the advantage of being simpler to implement and can still provide reasonably accurate solutions. It is also observed that both condition types can influence the flow field strongly and globally when the boundary is brought closer than 2.5 diameters from the body. In such cases the temporal periodicity of the solution is lost.     

Inhibition of Metalloproteinase Activity by Chinese Formulations Used to Treat Inflammatory Diseases

Introduction Matrixmetalloproteinases(MMPs)areaclassof zinc requiringextracellularendopeptidasesthatcanto getherdegradeallcomponentsoftheextracellularma trixandbasementmembranes[1—3].Theyplayimpor tantrolesinconnectivetissueremodeling,occurringin normalb…