The influence of bile salts on the distribution of simvastatin in the octanol/buffer system

Abstract

Introduction: Distribution coefficient (D) is useful parameter for evaluating drugs permeability properties across biological membranes, which are of importance for drugs bioavailability. Given that bile acids are intensively studied as drug permeation-modifying and -solubilizing agents, the aim of this study was to estimate the influence of sodium salts of cholic (CA), deoxycholic (DCA) and 12-monoketocholic acids (MKC) on distribution coefficient of simvastatin (SV) (lactone [SVL] and acid form [SVA]) which is a highly lipophilic compound with extremely low water solubility and bioavailability.

Methods: LogD values of SVA and SVL with or without bile salts were measured by liquid–liquid extraction in n-octanol/buffer systems at pH 5 and 7.4. SV concentrations in aqueous phase were determined by HPLC-DAD. Chem3D Ultra program was applied for computation of physico-chemical properties of analyzed compounds and their complexes.

Results: Statistically significant decrease in both SVA and SVL logD was observed for all three studied bile salts at both selected pH. MKC exerted the most pronounced effect in the case of SVA while there were no statistically significant differences between observed bile salts for SVL. The calculated physico-chemical properties of analyzed compounds and their complexes supported experimental results.

Conclusions: Our data indicate that the addition of bile salts into the n-octanol/buffer system decreases the values of SV distribution coefficient at both studied pH values. This may be the result of the formation of hydrophilic complexes increasing the solubility of SV that could consequently impact the pharmacokinetic parameters of SV and the final drug response in patients.     

Development of a water-in-oil-in-water multiple emulsion system integrating biomimetic aqueous-core lipid nanodroplets for protein entity stabilization. Part II: process and product characterization

The aqueous-core enclosed in lipid nanoballoons integrating multiple emulsions of the type water-in-oil-in-water mimic, at least in theory, the environment within viable cells, thus being suitable for housing hydrophilic protein entities such as bioactive proteins, peptides and bacteriophage particles. This study reports a complete physicochemical characterization of optimized biomimetic aqueous-core lipid nanoballoons housing hydrophilic (BSA) protein entities, evolved from a statistical 2³×3¹ factorial design study (three variables at two levels and one variable at three levels) that was the subject of the first paper of a series of three, aiming at complete stabilization of the three-dimensional structure of protein entities attempted via housing the said molecular entities within biomimetic aqueous-core lipid nanoballoons integrating a multiple (W/O/W) emulsion. The statistical factorial design followed led to the production of an optimum W/O/W multiple emulsion possessing quite homogeneous particles with an average hydrodynamic size of (186.2?±?2.6) nm and average Zeta potential of (?36.5?±?0.9) mV, and exhibiting a polydispersity index of 0.206?±?0.014. Additionally, the results obtained for the diffusion coefficient of the lipid nanoballoons integrating the optimized W/O/W multiple emulsion were comparable and of the same order of magnitude (10^?12 m² s^?1) as those published by other authors since, typically, diffusion coefficients for molecules range from 10^?10 to 10^?7 m² s^?1, but diffusion coefficients for nanoparticles are typically of the order of magnitude of 10^?12 m² s^?1.     

铜在碳钢中扩散及其对碳钢耐腐蚀性的影响

用水溶液电沉积法在碳钢表面电镀铜并进行高温扩散退火,用Den-Broeder法计算铜在碳钢中的扩散系数,研究了铜在碳钢中的扩散行为及其对碳钢耐腐蚀性的影响。结果表明,铜在碳钢中的扩散主要沿晶界进行,铜的扩散抑制了热处理过程中碳钢晶粒的长大。铜在碳钢中的扩散系数为1.11×10-16～3.03×10-11 cm2/s,扩散系数随着退火温度的提高而升高,随着铜浓度的提高而降低。铜在碳钢高温奥氏体区中扩散所需的激活能为126～167 kJ/mol,在高于低温铁素体+奥氏体混合区中激活能为90～108 kJ/mol。通过铜在碳钢中的扩散制备的Cu-Fe梯度材料,具有优良的耐腐蚀性。     

从测角后交最佳点位规律看规范规定之不足

本文分析了文献[1]所总结的测角后交两类公式在取得最佳点位时的规律,指出当前规范对此问题规定之不足.     

一种计算机专业课程考核方法

科学合理的考核方法对提高高校课程教学质量、检验教学效果起着重要的作用,课程的教学效果主要是通过考核来反映的。文章以"计算机组成原理与系统结构"课程为例,对高校计算机专业课程的考核模式进行探索,提出通过建立考核评价指标体系、调整指标权重系数,得到一种科学、公正的课程考核方法。     

An approach to quantify depth-resolved marine photochemical fluxes using remote sensing: Application to carbon monoxide (CO) photoproduction

This paper presents a model to calculate depth-resolved marine photochemical fluxes from remotely sensed ocean color and modeled solar irradiance. The basic approach uses three components: 1) below-sea-surface spectral downward scalar irradiance calculated from a radiative transfer model (STAR) and corrected for clouds using TOMS UV reflectivities; 2) surface-ocean spectral diffuse attenuation coefficients and absorption coefficients for chromophoric dissolved organic matter retrieved from SeaWiFS ocean color using the SeaUV/SeaUVc algorithms; and (3) spectral apparent quantum yield for the photochemical reaction considered. The output of the model is a photochemical rate profile, Ψ_PR(z), where z represents depth.We implemented the model for carbon monoxide (CO) photochemistry using an average apparent quantum yield spectrum and generated a monthly climatology of depth-resolved CO photoproduction rates in the global ocean. The climatology was used to compute global budgets and investigate the spatial and seasonal variabilities of CO photoproduction in the ocean. The model predicts a global CO photoproduction rate of about 41 TgC yr^− 1, in good agreement with other recent published estimates ranging from 30 to 84 TgC yr^− 1. The fate of photochemically derived CO and its role in global biogeochemical cycles remains uncertain however, with biological consumption and sea-air exchange competing for its removal in the surface ocean. Knowledge of the vertical distribution of CO photoproduction is critical in the quantification of the relative magnitudes of these sink mechanisms. The depth-resolution capabilities of this model, together with US Naval Research Laboratory climatology for mixed layer depths allowed further estimation that > 95% of the total water-column CO photoproduction occurs within the mixed layer on a global, yearly basis. Despite this compelling figure, the model also suggests significant spatio-temporal variability in the vertical distribution of CO photoproduction in the subtropical gyres, where up to 40% of water-column CO can be produced below the mixed layer during summertime.While the approach can be applied to other photochemical fluxes (e.g. DIC formation or DMS removal), accurate quantification of such processes with remote sensing will be limited until the mechanisms regulating observed oceanic variability in the apparent quantum yields are better understood. Minor modification to this model can also make it applicable for the determination of the effects of UV and visible solar radiation on sensitive biological systems.     

Two new control signal approaches for obtaining the MRAS-CDM and a real-time application

The coefficient diagram method (CDM) is one of the most effective control design methods. It creates control systems that are very stable and robust with responses without the overshoot and small settling time. Furthermore, all control parameters of the control systems are changed by varying some adjustment parameters in CDM depending on the demands. The model reference adaptive systems (MRAS) are the systems that follow and change the control parameters according to a given model reference system. There are several methods to combine the CDM with MRAS. One of these is to use the MRAS parameters as a gain of the CDM parameters. Another is to directly use the CDM parameters as the MRAS parameters. In the industrial applications, the system parameters can be changed frequently, but if the controller, by self-tuning, recalculates and develops its own parameters continuously, the system becomes more robust. Also, if the poles of the controlled systems approach the jw axis, the response of the closed-loop MRAS becomes more and more insufficient. In order to obtain better results, CDM is combined with a self-tuning model reference adaptive system. Systems controlled by a model reference adaptive controller give responses with small or without overshoot, have small settling times, and are more robust. Thus, in this paper, a hybrid combination of MRAS and CDM is developed and two different control structures of the control signal are investigated. The two methods are compared with MRAS and applied to real-time process control systems.     

粒子群优化算法中加速系数的实验分析

基于粒子群优化的原理,利用标准测试函数对粒子群算法的参数设计进行实验分析,依据函数特性进行初步分类,揭示不同类型优化问题中加速系数与惯性权重的相互关系及其设计规律。该项研究成果为粒子群算法的理论研究提供了实验依据,并为算法的实际应用创造了有利条件。     

室性早搏的多模板匹配自适应识别算法

为实现室性早搏的自动判别,提出一种基于多模板匹配的自适应识别算法。采用滤波提高数据信噪比,利用样本数据通过特定的自学习机制建立模板库,设计模板的压缩算法实现待测心搏与模板心搏宽度的对齐,采用模板队列匹配和模板库匹配相结合的匹配策略,设计自适应更新规则实时优化队列与库的结构,利用相关系数检测室早。使用MIT-BIH数据库进行测试,达到99.39%的灵敏度和98.79%的特异度。