Testing technologies performance stability

The first experiments with the thermal electric engine were conducted in Russia in 1929 by its inventor, Valentin P. Glushko, who later became a world-famous authority in rocket propulsion. For more than forty years, the United States and Russia have devoted many resources to research and development of various kinds of EREs. First tested in space by the Russians in 1964, these engines have found some limited applications in modern space technology. For more than two decades Russian weather and communication satellites have regularly used electric rocket engines for orbital stabilization. The first spacecraft to employ ERE for main propulsion was the American asteroid exploration probe Deep Space 1, launched in 1998. The performance of... 

Compared with the efforts spent on the low-temperature performance, less attention has been paid to the applications of lithium ion technology at elevated temperatures, with perhaps storage stability as the only exception. Cycling tests at temperatures above 50 °C have been rarely reported in the literature, most likely owing to the chemical instability of LiPFe in the organic solvents at elevated temperature and the difficulty of replacing it with new lithium salts. 

Costabilizers. In most cases the alkyltin stabilizers are particularly efficient heat stabilizers for PVC without the addition of costabilizers. Many of the traditional coadditives, such as antioxidants, epoxy compounds, and phosphites, used with the mixed metal stabilizer systems, afford only minimal benefits when used with the alkyltin mercaptides. Mercaptans are quite effective costabilizers for some of the alkyltin mercaptides, particulady those based on mercaptoethyl ester technology (23). Combinations of mercaptan and alkyltin mercaptide are currently the most efficient stabilizers for PVC extrusion processes. The level of tin metal in the stabilizer composition can be reduced by up to 50% while maintaining equivalent performance. Figure 2 shows the two-roll mill performance of some methyltin stabilizers in a PVC pipe formulation as a function of the tin content and the mercaptide groups at 200°C. The test formulation contains 100 parts of PVC (Fikentscher K = 65), 1.2 parts of paraffin wax, 0.6 parts of calcium stearate, and 0.4 parts of methyltin-based stabilizers. 

Early determination of PK properties (absorption, distribution, metabolism, excretion and toxicity, ADMET) has become a fundamental resource of medicinal chemistry in the LO phase. New technologies have been developed to perform a great number of in vitro and even in silico tests. Currently, the most common early-ADME assays evaluate both physicochemical properties (such as the solubility in an opportune medium, the lipophilicity, and the p K i) and biophysical properties (such as the permeability through cellular monolayers to predict oral absorption and the metabolic stability after treatment with liver or microsomal subcellular fraction that contains oxidative cytochromes). 

The current regulatory climate of QbD places an emphasis on clinically relevant specifications and methods for in vitro dissolution.20 Development scientists should identify dissolution methodology that has been closely examined for its relevance to in vivo performance, as well as for mechanistic information. In other words, the release mechanism of the product should be understood and the dissolution test should be able to detect changes reflecting deviation of the mechanism. There is also the quality control (QC) side of dissolution testing, which, until the process analytical technology (PAT) develops beyond the current capabilities, is very important for stability and end-product release testing. 

The CBPC technologies are not targeted for stabilizing organics, although several tests with Ceramicrete have shown that it performs better than other methods. Organics are generally destroyed by combustion or other chemical means, and their volume is reduced. The resultant ash or waste can then be immobilized in Ceramicrete. 

A more recently developed instrument is the microreaction calorimeter (Thermal Hazard Technology Ltd.). In this instrument, a smaller heat-shield is used around the sample, which permits very rapid changes in temperature at the expense of a slight decrease in sensitivity. The instrument uses a disposable glass ampoule with a rubber septum in the lid that allows provision for titration experiments to be performed. The versatility of the instrument means that it is particularly suited to stability and compatibility testing of pharmaceuticals, and a new six-calorimeter version that uses a common reference chamber is in development. 

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