Insitute of Experimental Physics, Faculty of Mathematics, Physics and Informatics, University of Gdańsk, Wita Stwosza 57, 80-308 Gdańsk, Poland.
Insitute of Experimental Physics, Faculty of Mathematics, Physics and Informatics, University of Gdańsk, Wita Stwosza 57, 80-308 Gdańsk, Poland.
Spectrochim Acta A Mol Biomol Spectrosc. 2023 Jan 5;284:121802. doi: 10.1016/j.saa.2022.121802. Epub 2022 Aug 31.
Diflunisal (5-(2,4-Difluorophenyl)salicylic acid, DIF), salicylic acid (SAL) derivative, which, on the one hand, is active pharmaceutical ingredient, on the other hand, belongs to the compounds exhibiting excited-state intramolecular proton transfer (ESIPT) behaviour was used to study the drug interactions with poly(vinyl alcohol) (PVA) matrix. For clarifying the nature and mechanisms of the drug-matrix interactions the salicylic acid (SAL) molecule was selected as the model active ESIPT compound, whose physicochemical properties in different media are well understood. The solute-solvent interactions (non-specific (dipole-dipole) versus specific (hydrogen bonding)) of DIF and SAL with different neat solvents were investigated using the steady-state spectroscopic technique. The solvent effect on spectral behaviours of DIF and SAL was analyzed based on the parametric solvent scales. In order to identify functional groups in the PVA matrices, determine the structure present in the studied molecule-PVA system and thus obtain information about the potential interactions between PVA and the studied molecules, the Raman spectra of pure PVA, SAL-PVA and DIF-PVA systems were measured. It has been shown that the molecular structure of the active substance entrapped in the polymer matrix affects the structure of the polymer, i.e., isotactic (SAL-PVA) versus syndiotactic (DIF-PVA) structure. The analysis of drug release kinetics revealed that the DIF is more strongly bound to PVA in comparison to SAL, which confirms conclusions drawn from the analysis of the Raman spectra i.e., the isotactic structure of SAL-PVA material results in a faster initial release process of weakly bound, located on the surface of the polymer SAL molecules.
双氟尼柳（5-(2,4-二氟苯基）水杨酸，DIF）是水杨酸（SAL）的衍生物，一方面是活性药物成分，另一方面属于表现出激发态分子内质子转移（ESIPT）行为的化合物，用于研究药物与聚乙烯醇（PVA）基质的相互作用。为了阐明药物-基质相互作用的性质和机制，选择水杨酸（SAL）分子作为模型活性 ESIPT 化合物，其在不同介质中的物理化学性质得到了很好的理解。使用稳态光谱技术研究了 DIF 和 SAL 与不同纯溶剂的溶质-溶剂相互作用（非特异性（偶极-偶极）与特异性（氢键））。基于参数溶剂尺度分析了溶剂对 DIF 和 SAL 光谱行为的影响。为了确定 PVA 基质中的官能团，确定研究分子-PVA 体系中的结构，从而获得 PVA 与研究分子之间潜在相互作用的信息，测量了纯 PVA、SAL-PVA 和 DIF-PVA 体系的拉曼光谱。结果表明，聚合物基质中包封的活性物质的分子结构影响聚合物的结构，即等规（SAL-PVA）与间规（DIF-PVA）结构。药物释放动力学分析表明，与 SAL 相比，DIF 与 PVA 的结合更强，这证实了拉曼光谱分析得出的结论，即 SAL-PVA 材料的等规结构导致结合较弱的 SAL 分子更快地初始释放，位于聚合物表面。
