{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:47:54Z","timestamp":1779911274884,"version":"3.53.1"},"reference-count":17,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,7,3]],"date-time":"2022-07-03T00:00:00Z","timestamp":1656806400000},"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>Pharmaceutical excipients should not interact with active substances, however, in practice, they sometimes do it, affecting the efficacy, stability and safety of drugs. Thus, interactions between active substances and excipients are not desirable. For this reason, two component mixtures of oral antidiabetic drug linagliptin (LINA) with four excipients of different reactivity, i.e., lactose (LAC), mannitol (MAN), magnesium stearate (MGS) and polyvinylpyrrolidone (PVP), were prepared in a solid state. A high temperature and a high humidity of 60 \u00b0C and 70% RH, respectively, were applied as stressors in order to accelerate the potential interactions between LINA and excipients. Differential scanning calorimetry (DSC) as well as Fourier transform infrared (FT-IR) and near infrared (NIR) spectroscopy were used to estimate the changes due to potential interactions. In addition, chemometric computation of the data with principal component analysis (PCA) and hierarchical cluster analysis (HCA) was applied to adequately interpret the findings. Of the excipients used in the present experiment, all of them were not inert in relation to LINA. Some of the interactions were shown without any stressing, whereas others were observed under high-temperature\/high-humidity conditions. Thus, it could be concluded that selection of appropriate excipients for LINA is very important question to minimize its degradation, especially when new types of formulations with LINA are being developed and manufactured.<\/jats:p>","DOI":"10.3390\/molecules27134283","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T20:59:18Z","timestamp":1656968358000},"page":"4283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["DSC, FT-IR and NIR with Chemometric Assessment Using PCA and HCA for Estimation of the Chemical Stability of Oral Antidiabetic Drug Linagliptin in the Presence of Pharmaceutical Excipients"],"prefix":"10.3390","volume":"27","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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Tr\u0119bacz","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Barzycka","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/ehjcvp\/pvv044","article-title":"Gliptins and their target dipeptidyl peptidase 4: Implications for the treatment of vascular disease","volume":"2","author":"Remm","year":"2016","journal-title":"Eur. Heart J. Cardiovasc. Pharm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1758-5996-5-25","article-title":"Linagliptin: Pharmacology, efficacy and safety in type 2 diabetes treatment","volume":"5","author":"Guedes","year":"2013","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"376","DOI":"10.3389\/fendo.2019.00376","article-title":"DPP-4 inhibition and the path to clinical proof","volume":"10","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12933-018-0704-1","article-title":"The role of dipeptidylpeptidase-4 inhibitors in management of cardiovascular disease in diabetes; focus on linagliptin","volume":"17","author":"Aroor","year":"2018","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_5","unstructured":"(2022, June 28). ICH Q1A (R2). Stability Testing of New Drug Substances and Products. Available online: https:\/\/www.ich.org\/page\/quality-guidelines."},{"key":"ref_6","unstructured":"(2022, June 28). ICH Guideline Q3A (R2). Impurities in New Drug Substances. Available online: https:\/\/www.ich.org\/page\/quality-guidelines."},{"key":"ref_7","unstructured":"(2022, June 28). ICH Guideline Q3B (R2). Impurities in New Drug Products. Available online: https:\/\/www.ich.org\/page\/quality-guidelines."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jpba.2013.06.016","article-title":"Drug-excipient compatibility screening-role of thermoanalytical and spectroscopic techniques","volume":"87","author":"Chadha","year":"2014","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1208\/s12249-017-0864-4","article-title":"Excipient stability in oral solid dosage forms: A review","volume":"19","author":"Darji","year":"2018","journal-title":"AAPS PharmSciTech"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"107","DOI":"10.4236\/ajac.2016.71011","article-title":"Drug-excipient interactions: Case studies and overview of drug degradation pathways","volume":"7","author":"Hotha","year":"2016","journal-title":"Am. J. Anal. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.jpba.2018.11.023","article-title":"Determination of chemical stability of sitagliptin by LC-UV, LC-MS and FT-IR methods","volume":"164","author":"Gumieniczek","year":"2019","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gumieniczek, A., Berecka-Rycerz, A., Fornal, E., \u017by\u017cy\u0144ska-Granica, B., and Granica, S. (2021). Comprehensive insight into chemical stability of important antidiabetic drug vildagliptin using chromatography (LC-UV and UHPLC-DAD-MS) and spectroscopy (mid-IR and NIR with PCA). Molecules, 26.","DOI":"10.3390\/molecules26185632"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"32","DOI":"10.5530\/jyp.2020.12s.43","article-title":"Formulation and evaluation of floating polymeric nanoparticles of linagliptin in capsules","volume":"12","author":"Prasanti","year":"2020","journal-title":"J. Young Pharm."},{"key":"ref_14","first-page":"6","article-title":"Thermo analytical study and purity determination of anti-diabetic drugs linagliptin and empagliflozin in drug substances","volume":"5","author":"Attia","year":"2020","journal-title":"Chem. Res. J."},{"key":"ref_15","first-page":"3","article-title":"Interactions and incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients; a comprehensive review","volume":"1","author":"Bharate","year":"2010","journal-title":"J. Excip. Food Chem."},{"key":"ref_16","unstructured":"Miller, J.N., and Miller, J.C. (2010). Statistics and Chemometrics for Analytical Chemistry, Pearson Education. [6th ed.]."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Leyk, E., and Wesolowski, M. (2021). Miscibility and solubility of caffeine and theophylline in hydroxypropyl methylcellulose. 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