Stress stability

Second, sensors are often intended for a single use, or for usage over periods of one week or less, and enzymes are capable of excellent performance over these time scales, provided that they are maintained in a nfild environment at moderate temperature and with minimal physical stress. Stabilization of enzymes on conducting surfaces over longer periods of time presents a considerable challenge, since enzymes may be subject to denaturation or inactivation. In addition, the need to feed reactants to the biofuel cell means that convection and therefore viscous shear are often present in working fuel cells. Application of shear to a soft material such as a protein-based film can lead to accelerated degradation due to shear stress [Binyamin and Heller, 1999]. However, enzymes on surfaces have been demonstrated to be stable for several months (see below). 

Liu, S. M., and G. Carpenter. Differential heat stress stability of epidermal growth factor receptor and erbB-2 receptor tyrosine kinase activities. J-Cell-Physiol. 157 237-42.1993. 

Comparative Stress Stability Studies for Rapid Evaluation of Manufacturing Changes or Materials from Multiple Sources... 

In this chapter, considerations are described for conducting comparative stress stability studies. Examples are presented to illustrate considerations and approaches for using stress conditions to compare sample stability. Finally, a statistical modeling approach is described, whereby the stability of a labile compound is modeled as a function of moisture and temperature. While requiring more time than some stress condition studies, this approach allows prediction of stability behavior over a wide range of conditions and ultimately saves time by eliminating the need for additional studies. 

Considerations involved in planning, conducting, and interpreting comparative stress stability studies are outlined in Table 1 and discussed below. 

Accelerated or stress stability studies for the purpose of predicting sample shelf life at normal conditions have been investigated for many years. In addition, some examples of stress stability studies for sample comparison have been described. Goldberg and Nightingale (25) compared the stability of aspirin in a combined dosage form with propoxyphene. The hydrolysis... 

The characterization of colloids depends on the purposes for which the information is sought, because the total description would be an enormous task. Among the properties to be considered are the nature and/or distributions of purity, crystallinity, defects, size, shape, surface area, pores, adsorbed surface films, internal and surface stresses, stability, and state of agglomeration [57,58],... 

Study stress stability for drug substance and proposed drug product. 

Is the method specific and stability indicating as shown by stressed stability (pH, light, heat, oxidation)studies ... 

Robustness, specificity (evaluated through stressed stability), and system suitability have been evaluated prior to the validation exercise and will be discussed in additional detail later. 

Is the method specific and stability indicating as shown by analysis of samples subjected to stressed stability studies (pH, light, heat, oxidation) Normally, specificity is determined through peak purity using ultraviolet (UV) diode array or liquid chromatography (LC)/mass spectrometry (MS) analysis. In methods for analysis of drug products, placebo formulations (and stressed placebos) must yield blank chromatographic baselines. The development... 

Additional preformulation and physicochemical characterization of the candidate compound are performed and stress stability studies may be initiated. Ideally, the optimal solid state (polymorphic) and chemical (salt) form of the molecule are identified as part of clinical candidate selection. Selection of the most stable and bioavailable form will expedite subsequent development. The methods for testing the drug substance are refined and additional methods may be developed. 

Figure 1. Stress stability (at 40 °C) and shelf life stability (at 10 °C) of the new 1,2-dioxetane derivative...

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