Stability studies accelerated testing

In thermal stability studies, accelerated testing at elevated temperatures is used to minimize the time needed to assess the thermal stability of the substance/ product. From the Arrhenius plot, one can predict the shelf life of the product at a proposed storage temperature. 

The plastic bottle and dispensing tip is made of low-density polyethylene (LDPE) resin, which provides the necessary flexibility and inertness. Because these components are in contact with the product during its shelf life, they must be carefully chosen and tested for their suitability for ophthalmic use. In addition to stability studies on the product in the container over a range of normal and accelerated temperatures, the plastic resins must pass the USP biological and chemical tests for... 

Similar to accelerated studies, stress tests give a general picture of the chemical stability and degradation pathways under exaggerated conditions, such as under extreme pH conditions (acids and bases), heat, oxidative or reductive conditions, hydrolysis, and light irradiation (light irradiation tests at not less than 1.2 million lux hours are formalized as described in ICH QIB). These mostly non-formalized stress tests are only evaluated over a short term, e.g., 1 month. 

Diehl, K.C., Hamann, D.D., and Whitfield, J.K. 1979. Textural failure in selected raw fruits and vegetables. J. Texture Studies 10 371-400. Fligner, K.L., Fligner, M.A., and Mangino, M.E. 1991. Accelerated tests for predicting long-term creaming stability of infant formula emulsion systems. Food Hydrocolloids 5 269-280. 

The oil stability index (OSI) method provides results in a matter of hours instead of months (required for studies done at ambient temperatures). These OSI results are useful as comparative measures of oxidative stability, i.e., to determine the effect of a treatment or antioxidant compared to a control sample. Meaningful predictions of the actual shelf lives of specific commodities require that such shelf life studies be performed at ambient conditions. If only accelerated tests are to be performed, two or more tests based on different principles of lipid oxidation measurement should be conducted the effect of accelerated storage temperature should also be investigated. 

Studies undertaken to elucidate the intrinsic stability of the drug substance. Such testing is part of the development strategy and is normally carried out under more severe conditions than those used for accelerated testing. 

Figure 1 Cartoon illustration of hypothetical chromatograms from stress testing (upper) and accelerated or long-term stability studies. Peaks A-I represent all the degradation products from stress-testing studies under various stress conditions and are therefore classified as potential degradation products. Peaks B-E and G represent the products that form at significant levels during formal stability studies and are therefore classified as the actual or relevant degradation products.

---