Quality by Design approach in the development of a solvent-modified micellar electrokinetic chromatography method: Finding the design space for the determination of amitriptyline and its impurities

A solvent-modified micellar electrokinetic chromatography method was set up for the simultaneous determination of the tricyclic antidepressant amitriptyline (AMI) and its main impurities. The method was developed following Quality by Design (QbD) principles according to ICH Guideline Q8(R2). QbD approach made it possible to find the design space (DS), where quality was assured. After a scouting phase, aimed at selecting a suitable capillary electrophoresis pseudostationary phase, risk assessment tools were employed to define the critical process parameters (CPPs) to be considered in a screening phase (applied voltage, concentration and pH of the background electrolyte, concentration of the surfactant sodium dodecyl sulphate, of the cosurfactant n-butanol and of the organic modifiers acetonitrile and urea). The effects of the seven selected CPPs on critical quality attributes (CQAs), namely resolution values between critical peak pairs and analysis time, were investigated throughout the knowledge space by means of a symmetric screening matrix. Response surface study was then carried out on four selected CPPs by applying a Doehlert Design. Monte-Carlo simulations were performed in order to estimate the probability of meeting the desired specifications on CQAs, and thus to define the DS by means of a risk of failure map. Additional points at the edges of the DS were tested in order to verify the requirements for CQAs to be fulfilled. A control strategy was implemented by defining system suitability tests. The developed method was validated following ICH Guideline Q2(R1), including robustness assessment by Plackett–Burman design, and was applied to the analysis of real samples of amitriptyline coated tablets.     

Nucleon polarizabilities in real and virtual Compton scattering: Recent theoretical issues

We review recent developments in the theoretical investigation of the nucleon polarizabilities. We first report on the static polarizabilities as measured in real Compton scattering, comparing and interpreting the results from various theoretical approaches. In a second step, we extend the discussion to the generalized polarizabilities which can be accessed in virtual Compton scattering, showing how the information encoded in these quantities can provide a spatial interpretation of the induced polarization densities in the nucleon.     

Aliphatic Anion Exchange Ionomers with Long Spacers and No Ether Links by Ziegler–Natta Polymerization: Properties and Alkaline Stability

In this work we report the synthesis of poly(vinylbenzylchloride-co-hexene) copolymer grafted with N,N-dimethylhexylammonium groups to study the effect of an aliphatic backbone without ether linkage on the ionomer properties. The copolymerization was achieved by the Ziegler–Natta method, employing the complex ZrCl₄ (THF)₂ as a catalyst. A certain degree of crosslinking with N,N,N′,N′-tetramethylethylenediamine (TEMED) was introduced with the aim of avoiding excessive swelling in water. The resulting anion exchange polymers were characterized by ¹H-NMR, FTIR, TGA, and ion exchange capacity (IEC) measurements. The ionomers showed good alkaline stability; after 72 h of treatment in 2 M KOH at 80 °C the remaining IEC of 76% confirms that ionomers without ether bonds are less sensitive to a S_N2 attack and suggests the possibility of their use as a binder in a fuel cell electrode formulation. The ionomers were also blended with polyvinyl alcohol (PVA) and crosslinked with glutaraldehyde. The water uptake of the blend membranes was around 110% at 25 °C. The ionic conductivity at 25 °C in the OH⁻ form was 29.5 mS/cm.     

冷冻干燥中升华界面移动的微CT实验研究

采用微CT扫描仪的扫描成像,图像重构及灰度值分析技术对不同厚度苹果片冷冻干燥的升华过程进行实验观察,分析了界面的移动特性.结果表明,对于单面传导加热的升华干燥过程,物料升华不仅在顶面进行,与搁板接触的底面以及侧面也会有水蒸气逸出.厚物料在升华过程中有一个明显的球形冻结区,升华界面呈三维模式逐渐向物料几何中心收缩.无论物料厚薄,刚开始升华干燥速率比较快,随着干燥层的增厚,升华过程的热质阻力增大,升华速率减慢.