Accelerated stability test

The routine compositional and functional testing done on the adhesives includes gas chromatographic testing for purity, potentiometric titrations for acid stabilizer concentrations, accelerated thermal stabiUty tests for shelf life, fixture time cure speed tests, and assorted ASTM tests for tensile shear strengths, peel and impact strengths, and hot strengths. 

Note A PTX-4 compn, prepd by the addition of Haleite to 30/70 Pentolite, also offered promise, but because of borderline stability in accelerated stability tests, it was decided that PTX-4 must be proven by long term storage to be acceptable for use in standard ammo Refs 1) W.R. Tomlinson, Properties of Ternary Mixtures of High Explosives PATR 1414 (1944) 2) A.J. Phillips, The Manufacture of... 

For liposomes with bilayers in either the gel or fluid state, hydrolysis kinetics could be adequately described by the Arrhenius equation (Fr kjaer et al., 1984 Grit et al., 1989). This finding opens the opportunity to perform accelerated stability tests to predict liposome stability at ambient temperatures or in the refrigerator provided that no fluid-to-gel transition of the bilayer occurs in the temperature range under investigation. 

Stability tests of catalyst. All catalysts deactivate during their life by various causes (see Chapter 3). The aim of stability tests is to examine the cause and rate of deactivation. These experiments are usually performed at conditions similar to those planned for the commercial unit. In some cases, accelerated tests are carried out using a feedstock with an elevated level of impurities or at a temperature significantly higher than that anticipated for the full-scale reactor. A laboratory reactor used for such tests is usually a down-scaled reactor or a part of the full-scale-reactor. Standard analytical equipment is used. 

The appearance of tablets and powders during accelerated stability testing can be quantified using tristimulus colorimetry [29]. In this work, various formulations were stored under stress conditions, and the tristimulus parameters... 

Finally, the protein assay for the drug product will also be used for realtime and accelerated stability testing if it has been validated to be stability indicating. A stability-indicating protein concentration method usually translates to a method that can reveal how much protein can be recovered from the dosage form. Many protein instabilities result in precipitation of the protein and adsorption to the container. An instability that results in only a modification of the protein structure but not in loss of protein from solution will not be detected by a sequence-independent protein assay such as a colorimetric assay. 

For a new drug application, a dataset of at least 12-month-long stability and a 6-month accelerated (or intermediate) stability, light irradiation results are required. The minimum frequency of 3 months in the first year, 6 months in the second year, and yearly stability tests thereafter are required. 

Accelerated stability testing by worsening the ambient conditions for the samples... 

Fig. 2.1 Accelerated stability testing. The percentage of drug remaining at elevated temperatures with time is measured (left) and the rate constants for the degradation reaction calculated. Using the Arrhenius relationship, a plot of the log of the rate constant against the reciprocal of absolute temperature of measurement yields a straight hne (right). Extrapolation of the Une permits calculation of the rate constant at lower temperatures and the prediction of shelf Ufe.

This accelerated stability test method is preferred by some fuel refiners and marketers over other test methods used to determine the stability of distillate fuel. The more severe test conditions, relatively short test time period, and similarity of this method to ASTM D-873, Oxidation Stability of Aviation Fuels (Potential Residue Method) contribute to its acceptance. 

Fig. 21.9 Correlation of conditions in accelerated stability testing with real-time testing (1 year at room temperature) [63]...

Selected experimental agents were subjected to an accelerated low-temperature stability test to determine the sensitivity of each sample to form solids. Samples that... 

Stability testing—Test one batch with three months of accelerated stability data in supplement and on batch on long-term stability. 

Chemistry—Application/compendial release requirements. Notification of change in batch size and submission of updated batch records to the FDA. One batch must be placed on accelerated stability testing and one on longterm stability. 

If significant change at any time during the 6-month period of the accelerated (shortterm) condition is observed, then stability testing at an intermediate condition is required and the extent of extrapolation will depend on the outcome of both the long-term and intermediate conditions ... 

An underlying assumption of the Arrhenius equation is that the reaction mechanism does not change as a function of temperature. Since accelerated stability testing of pharmaceutical products normally employs a narrow range of temperature, it is often difficult to detect nonlinearity in the Arrhenius plot from experimental data, even though such nonlinearity is expected from the reaction mechanism [7]. 

The stability of excipients is almost always taken for granted. Obviously, there is the potential for a phase change with certain lower melting excipients, e.g., semisolid materials, however, this is not a chemical phenomenon although it may enhance the potential for interaction by increasing the effective interface available at which the interaction can take place. However, some materials are not stable under conditions encountered in excipient compatibility screening or accelerated stability testing. A notable example is dibasic calcium phosphate dihydrate. At temperatures as low as 37°C, under certain conditions, the dihydrate can dehydrate to form the anhydrous material with the concomitant loss of water of crystallization (25), and at 25°C, it is a stable solid with a shelf life, when stored correctly, of more than two years. 

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