丙酸氯倍他索溶液稳定性研究

目的:考察不同pH条件下丙酸氯倍他索(clobetasol propionate,CBT)的稳定性,并利用人工神经网络对氯倍他索在设定条件下的(伪)一级降解速率常数进行预测。方法:根据化学动力学原理,采用经典恒温法进行试验,并通过高效液相色谱法测定氯倍他索的浓度;建立3层BP人工神经网络,并通过此经过训练的网络进行(伪)一级降解速率常数的预测。结果:丙酸氯倍他索溶液的降解反应属(伪)一级反应,绘制的pH-速度图是典型的V型,在pH为3.23条件下丙酸氯倍他索溶液最稳定,其预测的室温贮存有效期为761 d,pH条件明显影响丙酸氯倍他索溶液稳定性;根据本研究建立的3层BP人工神经网络(即2-15-1网络结构)所得到的一级降解速度常数预测值与常规方法得到的一级降解速度常数估算值之间具有良好的线性相关性。结论:本研究首次通过所建立和训练的人工神经网络,能够对丙酸氯倍他索的一级降解速率常数进行预测,预测结果和实际计算结果基本一致,故说明人工神经网络可以用于药物理化性质(如化学稳定性)的预测。

Chemical stability of the aqueous clobetasol propionate solution

Aim:To study pH-related chemical stability of clobetasol propionate,and exploit the potential of application of artificial neural networks(ANNs) in the prediction of first-order rate constants of clobetasol chemical degradation.Methods: An HPLC method was developed for the assay of the concentration in clobetasol aqueous solutions which were adjusted to a variety of pH.And according to the theory of chemical dynamics,the isothermal acceleration testing was used to evaluate the stability of the clobetasol propionate solution.ANNs with back-propagation algorithm,and exploif the potential of application of artificial neural networks in the predication of first-order rate constants of clopetasol chemical degradation,were exploited for the prediction of the rate constants.Results: It was found that the pH-dependent degradation of clobetasol propionate in the aqueous solution followed pseudo first-order kinetics and that a V-type pH-rate profile occurred.It also indicated that clobetasol was stable at pH of 3.23 with t_(0.9) being estimated to 761 days if placed under room temperature.Slight deviation from pH of 3.23 resulted in the severe degradation.There were linear relationships between the estimates of the first-order degradation rate constants by use of classical isothermal acceleration testing and the predicted values,based upon the trained three-layer back-propagation ANNs.Conclusion: The trained ANNs in this report provided good prediction of clobetasol stability within the margin of experimental setting,and ANNs have great potentials in the characterization of physicochemical properties of drug molecules,such as chemical stability.