Stress testing conditions

Perhaps the most dramatic variability in stress testing conditions is observed in the photo stressing of drugs (31), where the lamps and exposures... 

From the information provided above, it is apparent that stress-testing conditions have varied greatly from compound to compound and from investigator to investigator. Extremely harsh conditions have been commonly used in the past to ensure degradation, even if the conditions far exceeded plausible exposures. 

The results of the preliminary study were used to design the final stress testing study. Examination of the preliminary solid-state results indicates that the molecule appears to be stable under all of the solid-state conditions and therefore can be stressed at the maximum temperature (70°C) with a minimum number of time points. The preliminary solution results indicate that the molecule is susceptible to degradation particularly at the pH extremes at the upper temperature limit of 70°C. The temperature of 70°C appears to be appropriate for most conditions but will require time points shorter than seven days. The final screen was designed keeping these preliminary results in mind. Tables 10-12 list the final stress-testing conditions, time points, and results. The HPLC method used for the final screen is given in Table 13. 

I. Stress-Testing Conditions and Sample Preparation. 141 IE Methods of Analysis. 160 III. Conclusions. 170 References. 171... 

According to the thermal/humidity stress testing conditions selected, samples are placed into appropriate ovens. If humidity ovens capable of 70°C/30% RH and 70°C/75% RH are not available, saturated salt solutions contained in desiccators can be used to control humidity accurately. These conditions are particularly useful for high-potency drug substance compounds for which samples must be contained. A saturated NaCl solution is used to obtain conditions of 75% RH at 70 °C and a saturated MgCl2 solution is used to obtain conditions of 30% RH at 70 °C. 

Accelerated stability studies are potentially problematic for at least three reasons. Stress testing conditions may exceed the temperature of a polymorphic phase transition or dehydration. The use of accelerated conditions may make a relaxation of a metastable phase more rapid due to the increased molecular mobility. Finally, the relative humidity of the station may be in the range sufficient to cause a pseudopolymorphic transition due to dehydration or hydration. It is sobering... 

FIG. 28 Moisture up-take curves for several typical EGA and CSP components under stress test conditions (30 C, 60% RH). (Courtesy of Universal Instruments Corporation). 

Tests using a constant stress (constant load) normally by direct tension have been described in ISO 6252 (262). This test takes the specimen to failure, or a minimum time without failure, and frequently has a flaw (drilled hole or notch) to act as a stress concentrator to target the area of failure. This type of testing, as well as the constant strain techniques, requires careful control of specimen preparation and test conditions to achieve consistent results (263,264). 

Fig. 2. Schematic of energy dissipation in a commonly used peel test. The energy dissipation can occur in the adhesive and/or the adherends. The extent of energy dissipation depends on the elasto-plastic properties of the adhesive and the adherends under the test conditions as well as the local stresses and strains near the crack tip.

MFI of the composition to that of the matrix, as a function of the filler concentration. It can be seen that, as the concentration of a particular filler increases, the index increases too for one matrix but decreases for another, and varies by a curve with an extremum for a third one. Even for one and the same polymerfiller system and a fixed concentration of filler, the stress-strain characteristics, such as ultimate stress, may, depending on the testing conditions (temperature, rate of deformation, etc.) be either higher or lower than in the reference polymer sample [36],... 

Creep modeling A stress-strain diagram is a significant source of data for a material. In metals, for example, most of the needed data for mechanical property considerations are obtained from a stress-strain diagram. In plastic, however, the viscoelasticity causes an initial deformation at a specific load and temperature and is followed by a continuous increase in strain under identical test conditions until the product is either dimensionally out of tolerance or fails in rupture as a result of excessive deformation. This type of an occurrence can be explained with the aid of the Maxwell model shown in Fig. 2-24. 

When materials are evaluated against each other, the flexural data of those that break in the test cannot be compared unless the conditions of the test and the specimen dimensions are identical. For those materials (most TPs) whose flexural properties are calculated at 5% strain, the test conditions and the specimen are standardized, and the data can be analyzed for relative preference. For design purposes, the flexural properties are used in the same way as the tensile properties. Thus, the allowable working stress, limits of elongation, etc. are treated in the same manner as are the tensile properties. 

Storage conditions will be used. Standard conditions to simulate normal storage are temperatures of 25 or 30 °C and relative humidity of 60 or 65%. A minimum of 12 months real-time data is required for a marketing authorisation application. Real-time data should be supported by accelerated and intermediate stress testing at higher temperature/relative humidity. Photostability should be verified using a single batch. 

This is determined by applying a suitable design stress factor (factor of safety) to the maximum stress that the material could be expected to withstand without failure under standard test conditions. The design stress factor allows for any uncertainty in the design methods, the loading, the quality of the materials, and the workmanship. 

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