Fernández de Aránguiz M Yolanda, de la Torre Sofía, Berraondo M Rosario
Department of Physical Chemistry, Faculty of Pharmacy, University of the Basque Country (U.P.V./EHU), Paseo de la Universidad, 7, 01006 Vitoria-Gasteiz, Spain.
Eur J Pharm Sci. 2007 Aug;31(5):277-87. doi: 10.1016/j.ejps.2007.04.004. Epub 2007 Apr 24.
Non-isothermal degradations were applied to carry out simulation studies to analyse the influence of some factors on the accuracy and precision of stability parameters of drugs, to establish the best work conditions in experimental studies of stability using non-isothermal methodology. These factors were: random error added, sampling frequency, heating model, extent of drug degradation, amplitude of temperature range and mean temperature. Simulation studies were realized for a first-order degradation process. A weighted non-linear regression was used to determine the stability parameters which were statistically evaluated. An ANOVA analysis and post hoc comparisons tests were made to determine the statistical significance of the influence of each factor studied on the central value and on the precision of stability parameters of drugs. Univariant general linear model allowed to establish quantitatively the effect of the variability of the factors studied on the variability on the precision of the kinetic parameters. It was found that the influence of the studied factors was not statistically significant (p>0.05) on the activation energy (E(a)) and shelf-life (t(90)) values. Nevertheless, four of the six analysed factors influenced with statistical significance on the precision of the shelf-life according the following decreasing order of importance: random error added, extent of drug degradation, amplitude of temperature range and heating model.
采用非等温降解进行模拟研究，以分析某些因素对药物稳定性参数准确性和精密度的影响，从而确定使用非等温方法进行稳定性实验研究的最佳工作条件。这些因素包括：添加的随机误差、采样频率、加热模型、药物降解程度、温度范围幅度和平均温度。针对一级降解过程进行了模拟研究。采用加权非线性回归确定稳定性参数，并进行统计评估。进行方差分析和事后比较检验，以确定所研究的每个因素对药物稳定性参数中心值和精密度影响的统计学显著性。单变量通用线性模型能够定量确定所研究因素的变异性对动力学参数精密度变异性的影响。结果发现，所研究的因素对活化能（E(a)）和有效期（t(90)）值的影响无统计学显著性（p>0.05）。然而，六个分析因素中有四个对有效期精密度有统计学显著影响，其重要性从高到低依次为：添加的随机误差、药物降解程度、温度范围幅度和加热模型。
