Stability accelerated testing

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. 

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. 

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]...

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. 

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. 

The dibasic calcium phosphate dihydrate example discussed above is probably an extreme example of the instability of an excipient relating to the release of water. But many excipients exist in a hydrated state, and heating them for the purposes of compatibility studies, or accelerated stability testing, can cause any free water, and sometimes other types of water, to be released, which can then influence any potential interaction, or even interact itself with the drug. 

Prior approval supplement (all information including accelerated stability test data) annual report (long-term stability data). 

An accelerated stability test to monitor the rate of color development in MMBS resins under heat aging conditions in an oxygen deficient environment has been described (12). In plaque form, the... 

Accelerated stability tests using the emulsion volume index (EVI) Accelerated aging procedure in which an emulsion in a microhematocrit tube is subjected to centrifugal force EVI = (length of emulsion phase/lolul length of column) (% fal/0.9) x 100. A higher EVI indicates a more stable emulsion under the conditions of the test. 

Pope DG. Accelerated stability testing for prediction of drug product stability. Drug and Cosmet. Ind., Part 1, 54-62, November, 1980 and Part 2, 48-116, December 1980. 

Yang W-H, Roy SB. Projection of tentative expiry date from one-point accelerated stability testing. Drug Dev Ind Pharm 1980 6(6) 591-604. 

Davis JS. Criteria for Accelerated Stability Testing, presented at the FDA/ ASQC Seminar, March 11, Chicago, IL, 1991. 

Stamper GF, Lambert WJ. Accelerated stability testing of proteins and peptides pH-stability profile of insulinoptropin using traditional Arrhenius and non-linear fitting analysis. Drug Dev Ind Pharm 1995 21 1503-1511. 

Yang W. Errors in the estimation of the activation energy and the projected shelf life in employing an incorrect kinetic order in an accelerated stability test. Drug Dev Ind Pharm 1981 7 717-738. 

Franks F. Accelerated stability testing of bioproducts attractions and pitfalls. Trends Biotechnol 1994 12 114—117. 

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