{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:47:19Z","timestamp":1760060839533,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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, w\/w) 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 \u00b0C\/80% RH and UV\/Vis light in the dose 94.510 kJ\/m2). 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.<\/jats:p>","DOI":"10.3390\/molecules30183807","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T08:11:01Z","timestamp":1758269461000},"page":"3807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spectroscopic and Chemometric Evaluation of the Stability of Timolol, Naphazoline, and Diflunisal in the Presence of Reactive Excipients Under Forced Degradation Conditions"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2503-5272","authenticated-orcid":false,"given":"Anna","family":"Gumieniczek","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3577-1377","authenticated-orcid":false,"given":"Marek","family":"Wesolowski","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy, Medical University of Gdansk, Gen. J. Hallera 107, 80-416 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5914-6289","authenticated-orcid":false,"given":"Anna","family":"Berecka-Rycerz","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4588-1588","authenticated-orcid":false,"given":"Edyta","family":"Leyk","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy, Medical University of Gdansk, Gen. J. Hallera 107, 80-416 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"key":"ref_1","unstructured":"(2025, January 20). Timolol. 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