The Arrhenius equation is a formula for the temperature dependence of reaction rates based on the work of Jacobus Henricus Van't Hoff in the late 19th century. Experience indicates that some pharmaceutical analytes have activation energy in the range of 10 to 20 kcal/mol, but it is unlikely you will have precise information or be able to make assumptions about the activation energy of a certain product. 1 0 obj <>]/Pages 3 0 R/Type/Catalog/ViewerPreferences<>>> endobj 2 0 obj <>stream
Q1A(R2). More details on this issue are found in references 9 and 10. Since no closed-form solutions for ML estimates exist, an iterative procedure is performed, starting with some initial values for the parameters and updating them until differences between consecutive iterations are minimal and the estimates converge to their final value. A critical level of C = 0.8 is the criterion. Accelerated Ageing for Medical Device Packs What Temperature. Rockville (MD); 1987. During an accelerated ageing study, packs are usually stored at 55°C.
Several methods of predicting shelf life based on accelerated stability testing are described in the article. Assuming that the degradation pattern follows a first-order reaction as described in Equation 2, the Arrhenius equation (Equation 4) can be used to predict the degradation rate at recommended storage temperature. Temperature is the most common acceleration factor used for chemicals, pharmaceuticals, and biological products because its relationship with the degradation rate is characterized by the Arrhenius equation. Statistics that test the appropriateness of this approximation are presented in literature. Stability parameter estimation at ambient temperature from studies at elevated temperatures. Looks like you’ve clipped this slide to already. Common TAAs are +50ºC, +55ºC, and +60ºC.
However, when the activation energy is known, the degradation rate at storage temperature may be predicted from data collected at only one elevated temperature. BPI. The bracket method is a straightforward application of the Arrhenius equation that can be used if the value of the activation energy is known.12 Assuming that stability of a product at 50°C is 32 days, and it will be stored at 25°C, then, te = 32 days, Te = 273 + 50°C = 323K, and Ts = 273 + 25°C = 298K. J Biopharm Stat 2003; 13:431-449. Theoretically, the Arrhenius equation does not apply when more than one kind of molecule is involved in reactions. Shelf life is commonly estimated using two types of stability testing: real-time stability tests and accelerated stability tests.
A zero- or first-order kinetics reaction takes place at each elevated temperature as well as at the recommended storage temperature. \text { Accelerated Aging Time } (A A T)=\frac{\text { Desired Real Time }(R T)}{Q_{10} \scriptsize\left[\left(T_{A A}-T_{R T}\right) / 10\right]} Currently, it is best seen as an empirical relationship. Degradation at storage temperature can be predicted from the degradation at elevated temperatures as. The testing result (Y) will include random components representing lot-to-lot variability and experimental error. and ICH has published some guidelines for advanced testing design and data analysis. 2016-06-24T07:32:37+02:00 The Arrhenius equation is explained in detail courtesy of the Khan Academy. Polymers are often kept at elevated temperatures, in order to accelerate chemical breakdown. Stability at recommended storage temperature is calculated with a modified version of Equation 5 as: Calculated stability is highly dependent on the value of activation energy. DRUG STABILITY The performance of each lot at each time point is measured in three replicates. When most of the assumptions required to use the Arrhenius equation are not satisfied, comparisons to a product with a known stability is performed to assess shelf life. Each product has a specific mode of spoilage (i.e. 4.
to speed up the normal aging processes of items.
1. This process is carried out according to guidelines given in ASTM F1980 - Standard Guide for Accelerated Ageing of Sterile Medical Device Packages.
Accelerated stability model for predicting shelf-life. J Pharm Sci 2001; 90:1759-1766. We will send you newsletters that you can opt-out for at anytime. The number of days that the product remains stable at the recommended storage conditions is referred to as the shelf life. The calculated AAT is typically rounded up to the nearest whole day.
Real Time assessment is usually time and resource consuming. ���;O$���`��ڑMݬD)"���:��Y=/# It is not reasonable to test at very high temperatures for a very short period of time, since the mechanisms of degradation at high temperatures may be very different than those at the recommended storage temperature. The product loses its activity as it ages, but it is considered to be performing within the specification until it reaches 80% of its activity (C = 0.8).
default We recommend using the maximum likelihood (ML) approach to estimate these parameters. adobe:docid:indd:073d996b-7b6b-11e2-9622-c43a0c133bf5 This represents the lower 95% confidence limit corresponding to the estimated time of 541 days. Q1A(R). Select temperature levels based on the nature of the product and the recommended storage temperature. Accelerated Aging Calculator.
However, RH should be kept under 30% so material is not damaged.
Adobe InDesign CS6 (Windows) Predictions at 25°C based on the Arrhenius equation are presented in Table 3.
Although it is common to approximate these reactions with an exponential relationship, sometimes their degradation pattern needs to be modeled more precisely, and no shortcuts will suffice. Bracketing and matrixing designs for stability testing of new drug substances and products. Humidity and pH can be used along with temperature to accelerate degradation, but modeling of multi-factor degradation is very complex. (9) Magari R. Estimating degradation in real time and accelerated stability tests with random lot-to-lot variation: a simulation study. Recent issues in stability testing, J Biopharm Stat 2003; 13:vii-ix. �q����s�B��fi�*I��p��s�9gk�͞�NGu��/��7�Ξ\� �Y�4��U|��0$2C���]�����J��*Y�U)��R��j�6#!E��T�%��Âer�Z��he�j��:^�Ҩ�SdA� ���aᇵ A historically useful overview supported by Arrhenius' equation is that, for many common chemical reactions at room temperature, the reaction rate doubles for every 10° Celsius increase in temperature. Geneva; 2003.