Zhou Deliang, Schmitt Eric A, Zhang Geoff G Z, Law Devalina, Wight Charles A, Vyazovkin Sergey, Grant David J W
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455-0343, USA.
J Pharm Sci. 2003 Jul;92(7):1367-76. doi: 10.1002/jps.10400.
The conventional model-fitting approach to kinetic analysis assumes a fixed mechanism throughout the reaction and therefore may be too simplistic for many solid-state reactions. Even for a reaction with a fixed mechanism, model fitting sometimes cannot identify the reaction model uniquely. The alternative model-free approach is sufficiently flexible to allow for a change of mechanism during the course of a reaction and therefore provides a more realistic treatment of solid-state reactions kinetics. The application of model-free analysis to solid-state dehydrations was investigated using the two consecutive dehydration reactions of nedocromil sodium trihydrate. The complexity of such reactions is illustrated by the variation of the activation energy as each dehydration proceeds. The 1st-step dehydration follows one-dimensional phase boundary kinetics until the fraction dehydrated reaches 0.75, and deviates from this model thereafter. The 2nd-step dehydration follows a mechanism intermediate between two- and three-dimensional diffusion that cannot be described by any of the common models. The model-free approach is clearly better than the model-fitting approach for understanding the details of these solid-state dehydration reactions.
传统的动力学分析模型拟合方法假定在整个反应过程中反应机理固定，因此对于许多固态反应而言可能过于简单。即使对于具有固定反应机理的反应，模型拟合有时也无法唯一地确定反应模型。另一种无模型方法足够灵活，能够考虑反应过程中反应机理的变化，因此能更实际地处理固态反应动力学。使用奈多罗米钠三水合物的两个连续脱水反应研究了无模型分析在固态脱水反应中的应用。随着每次脱水反应的进行，活化能的变化说明了此类反应的复杂性。第一步脱水遵循一维相边界动力学，直至脱水分数达到0.75，此后偏离该模型。第二步脱水遵循介于二维和三维扩散之间的反应机理，无法用任何常见模型描述。对于理解这些固态脱水反应的细节而言，无模型方法显然优于模型拟合方法。
