Department of Chemistry, University of Alabama at Birmingham, 901 S. 14th Street, Birmingham, AL 35294, USA.
Department of Chemistry, University of Alabama at Birmingham, 901 S. 14th Street, Birmingham, AL 35294, USA.
Int J Pharm. 2018 Nov 15;551(1-2):111-120. doi: 10.1016/j.ijpharm.2018.09.020. Epub 2018 Sep 11.
The present study explores the hypothesis that a polymer can affect the thermal stability of a drug in solid polymer-drug dispersions. The hypothesis is tested in a systematic fashion by combining isoconversional kinetic analysis with thermogravimetric measurements on several solid dispersions. Experimental systems involve three drugs: indomethacin (IMC), felodipine (FD), and nifedipine (ND) and their solid dispersions with polyvinylpyrrolidone (PVP). It is found that PVP stabilizes IMC but destabilizes FD and ND. Isoconversional kinetic analysis provides insights into the origin of the observed effects. The enhanced thermal stability of IMC in the PVP matrix is associated with an increase in the activation energy of the respective degradation process. A detrimental effect of the PVP matrix on the stability of FD and ND has been linked to a decrease in the activation energy and an increase in the preexponential factor, respectively. The molecular underpinnings of the observed effects are discussed. It is concluded that the effects in question are of relevance for drug performance and need to be taken into account in preformulation studies.
本研究探索了一种假设，即聚合物可以影响固体聚合物-药物分散体中药物的热稳定性。通过将等转化率动力学分析与几种固体分散体的热重测量相结合，以系统的方式检验了这一假设。实验系统涉及三种药物：吲哚美辛（IMC）、非洛地平（FD）和硝苯地平（ND）及其与聚乙烯吡咯烷酮（PVP）的固体分散体。结果发现，PVP 稳定了 IMC，但使 FD 和 ND 不稳定。等转化率动力学分析为观察到的效应的起源提供了深入的了解。在 PVP 基质中，IMC 的热稳定性增强与各自降解过程的活化能增加有关。PVP 基质对 FD 和 ND 稳定性的不利影响与活化能的降低和指数前因子的增加分别相关。讨论了观察到的效应的分子基础。结论认为，所讨论的这些效应与药物性能有关，在制剂前研究中需要考虑到这些效应。
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