Gumieniczek Anna, Wesolowski Marek, Berecka-Rycerz Anna, Leyk Edyta
Department of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland.
Department of Analytical Chemistry, Faculty of Pharmacy, Medical University of Gdansk, Gen. J. Hallera 107, 80-416 Gdansk, Poland.
Molecules. 2025 Sep 19;30(18):3807. doi: 10.3390/molecules30183807.
It was previously demonstrated that timolol (TIM), naphazoline (NAPH), and diflunisal (DIF) are susceptible to degradation when exposed to extreme pH conditions and UV/Vis light. However, their stability in the presence of pharmaceutical excipients remains largely unexplored. Thus, their binary mixtures (1:1 ratio, /) with five excipients, hydroxyethyl cellulose (HCA), mannitol (MAN), poly(vinyl alcohol) (PVA), poly(vinylpyrrolidone) (PVP), and Tris HCl (TRIS), were subjected to forced degradation (70 °C/80% RH and UV/Vis light in the dose 94.510 kJ/m). Forced degradation was designed to accelerate potential interactions between these compounds, allowing the earlier identification of degradation risk compared to formal stability studies. FT-IR/ATR and NIR spectroscopy, along with chemometric evaluation using Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA), was applied to assess changes in the spectra, compared to individual compounds and the non-stressed mixtures. A hybrid approach, combining visual assessment with chemometric evaluation of the spectral data, enabled the detection of changes that were not clearly observable using a single analytical method. In particular, interactions of TIM, NAPH, and DIF with MAN and TRIS were clearly identified, while the mixtures of NAPH with excipients proved to be the least sensitive to forced degradation.
先前已证明，噻吗洛尔（TIM）、萘甲唑啉（NAPH）和二氟尼柳（DIF）在暴露于极端pH条件和紫外/可见光时易发生降解。然而，它们在药物辅料存在下的稳定性在很大程度上仍未得到探索。因此，将它们与五种辅料羟乙基纤维素（HCA）、甘露醇（MAN）、聚乙烯醇（PVA）、聚乙烯吡咯烷酮（PVP）和三羟甲基氨基甲烷盐酸盐（TRIS）的二元混合物（1:1比例，/）进行强制降解（70℃/80%相对湿度以及剂量为94.510 kJ/m的紫外/可见光照射）。强制降解旨在加速这些化合物之间的潜在相互作用，与正式的稳定性研究相比，能够更早地识别降解风险。应用傅里叶变换红外光谱/衰减全反射（FT-IR/ATR）和近红外光谱，以及使用主成分分析（PCA）和层次聚类分析（HCA）的化学计量学评估，来评估与单个化合物和未受胁迫混合物相比光谱的变化。一种将视觉评估与光谱数据的化学计量学评估相结合的混合方法，能够检测出使用单一分析方法无法清晰观察到的变化。特别是，明确识别出了TIM、NAPH和DIF与MAN和TRIS的相互作用，而NAPH与辅料的混合物被证明对强制降解最不敏感。
