{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T19:07:04Z","timestamp":1772305624564,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T00:00:00Z","timestamp":1638921600000},"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>Cyclodextrins have found wide application in contemporary chemistry, pharmacy and medicine. Because of their unique properties, cyclodextrins are constantly used in research on solubility or stability improvement, as well as other physicochemical properties of medicinal substances. Indomethacin (IND) is a photolabile molecule that also attracts the interest of researchers due to its therapeutic potential and the need to overcome its problematic photosensitivity. Supramolecular complexes of indomethacin with \u03b2-cyclodextrin (CD) are already known, and they show greater stability compared to complexes with other types of cyclodextrins. So far, however, the sensitivity to light of physical mixtures and inclusion complexes in the solid phase has not been studied, and their various stoichiometries have not yet been investigated. Due to this fact, the aim of the present study is to obtain supramolecular systems (inclusion complexes and physical mixtures) of indomethacin with three different amounts of \u03b2-cyclodextrin. Assessment of the photochemical stability of indomethacin-\u03b2-cyclodextrin systems in the solid state is performed in order to find the best correlation between IND stability and the amount of CD. Comparative analysis of physicochemical degradation for stoichiometry systems [CD:IND] = [1:1], [0.5:1] and [0.1:1] is performed by using ultraviolet spectroscopy, transmission\u2014FTIR, reflection\u2014ATR-FTIR infrared spectroscopy and DSC calorimetry.<\/jats:p>","DOI":"10.3390\/molecules26247436","type":"journal-article","created":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T23:30:00Z","timestamp":1639006200000},"page":"7436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Preparation and Characterization of Indomethacin Supramolecular Systems with \u03b2-Cyclodextrin in Order to Estimate Photostability Improvement"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2637-9886","authenticated-orcid":false,"given":"Marzena","family":"Jamr\u00f3giewicz","sequence":"first","affiliation":[{"name":"Department of Physical Chemistry, Faculty of Pharmacy, Medical University of Gda\u0144sk, Al. Gen. Hallera 107, 80-416 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0607-986X","authenticated-orcid":false,"given":"Marek","family":"J\u00f3zefowicz","sequence":"additional","affiliation":[{"name":"Institute of Experimental Physics, Faculty of Mathematics, Physics and Informatics, University of Gda\u0144sk, Wita Stwosza 57, 80-308 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1208\/s12249-017-0869-z","article-title":"Photostability issues in pharma-ceutical dosage forms and photostabilization","volume":"19","author":"Janga","year":"2018","journal-title":"Pharm. Sci. Tech."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-5173(01)00746-3","article-title":"Formulation and stability testing of photolabile drugs","volume":"225","year":"2001","journal-title":"Int. J. Pharm."},{"key":"ref_3","first-page":"5095","article-title":"Improvement of photostability in for-mulation: A review","volume":"20","author":"Bhalekar","year":"2008","journal-title":"Asian J. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0378-5173(03)00268-0","article-title":"Niosomes as carriers for tretinoin: II. Influence of vesicular incorporation on tretinoin photostability","volume":"260","author":"Manconi","year":"2003","journal-title":"Int. J. Pharm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ijpharm.2003.07.001","article-title":"Design and monitoring of photostability systems for amlodipine dosage forms","volume":"265","author":"Ragno","year":"2003","journal-title":"Int. J. Pharm."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.ijpharm.2017.11.018","article-title":"Cyclodextrins: Structure, physicochemical properties and pharmaceutical applications","volume":"535","author":"Jansook","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1080\/10717544.2017.1386733","article-title":"Photosensitive drugs: A review on their photoprotection by lipo-somes and cyclodextrins","volume":"24","author":"Ioele","year":"2017","journal-title":"Drug Deliv."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dahabra, L., Broadberry, G., Le Gresley, A., Najlah, M., and Khoder, M. (2021). Sunscreens containing cyclodextrin inclusion complexes for enhanced efficiency: A strategy for skin cancer prevention. Molecules, 26.","DOI":"10.3390\/molecules26061698"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"De Luca, M., Ioele, G., and Ragno, G. (2019). Review: 1,4-Dihydropyridine antihypertensive drugs: Recent advances in photo-stabilization strategies. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11020085"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0378-5173(98)00283-X","article-title":"Complexation of the sunscreen agent, bu-tyl-methoxydibenzoylmethane, with hydroxypropyl-\u03b2-cyclodextrin","volume":"175","author":"Scalia","year":"1998","journal-title":"Int. J. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Carneiro, S.B., Costa Duarte, F.\u00cd., Heimfarth, L., Siqueira Quintans, J.D.S., Quintans-J\u00fanior, L.J., Veiga J\u00fanior, V.F.D., and Neves de Lima, \u00c1.A. (2019). Cyclodextrin\u2013drug inclusion complexes: In vivo and in vitro approaches. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030642"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s13346-018-0591-8","article-title":"Synthesis and characterization of a new cyclodextrin derivative with improved properties to design oral dosage forms","volume":"9","author":"Priotti","year":"2019","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1007\/s10311-018-0763-2","article-title":"Cyclodextrins, from molecules to applications","volume":"16","author":"Crini","year":"2018","journal-title":"Environ. Chem. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1080\/13543776.2017.1384816","article-title":"Cy-clodextrins improving the physicochemical and pharmacological properties of antidepressant drugs: A patent re-view","volume":"28","author":"Diniz","year":"2018","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.2174\/1381612824666171218125431","article-title":"Cyclodextrins as drug carriers in pharmaceutical tech-nology: The state of the art","volume":"24","author":"Conceicao","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2006.10.044","article-title":"Cyclodextrins and their pharmaceutical applications","volume":"329","author":"Loftsson","year":"2007","journal-title":"Int. J. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3181\/00379727-167-41142","article-title":"Treatment of chemically-induced intestinal cancers with indometacin","volume":"167","author":"Pollard","year":"1981","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_18","first-page":"2243","article-title":"Indometacin inhibits the proliferation and activation of human pancreatic stellate cells through the downregulation of COX-2","volume":"39","author":"Sun","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.3892\/ol.2013.1560","article-title":"Screening for novel protein targets of indomethacin in HCT116 human co-lon cancer cells using proteomics","volume":"6","author":"Cheng","year":"2013","journal-title":"Oncol. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/1010-6030(91)85071-N","article-title":"The photochemistry of indomethacin","volume":"61","author":"Weedon","year":"1991","journal-title":"J. Photochem. Photobiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/j.1751-1097.1993.tb09576.x","article-title":"Spectroscopic studies of cutaneous photosensitizing agents","volume":"58","author":"Dabestani","year":"1993","journal-title":"Photochem. Photobiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.jpba.2011.07.005","article-title":"Determination of photostability and photodegradation products of indomethacin in aqueous media","volume":"56","author":"Temussi","year":"2011","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"232","DOI":"10.2478\/s11532-011-0133-4","article-title":"A study of photodegradation of quetiapine by the use of LC-MS\/MS method","volume":"10","year":"2012","journal-title":"Open Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1002\/bmc.3625","article-title":"Characterization of paliperidone photodegradation products by LC-Q-TOF multistage mass spectrometry","volume":"30","author":"Komsta","year":"2016","journal-title":"Biomed. Chromatogr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1023\/A:1015860531565","article-title":"Effect of cyclodextrin derivates on indomethacin stability in aqueos solution","volume":"7","author":"Backensfeld","year":"1990","journal-title":"Pharm. Res."},{"key":"ref_26","unstructured":"(2021, September 01). International Conference on Harminisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Guideline: Stability Testing Photostability Testing of New Drug Substances and Products, Q1B. Available online: https:\/\/database.ich.org\/sites\/default\/files\/Q1B%20Guideline.pdf."},{"key":"ref_27","unstructured":"(2003). ICH Stability Testing: Photostability testing of new drug substances and products Q1B. Int. Conf. Harmon., 24, Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/ich-q-1-r2-stability-testing-new-drug-substances-products-step-5_en.pdf."},{"key":"ref_28","first-page":"00073","article-title":"Forced degradation studies","volume":"3","author":"Iram","year":"2016","journal-title":"J. Anal. Pharm."},{"key":"ref_29","first-page":"17","article-title":"Consequences of new approach to chemical stability tests to active pharmaceutical ingredients","volume":"7","year":"2016","journal-title":"Front. Pharmacol."},{"key":"ref_30","first-page":"1","article-title":"How to approach a forced degradation study","volume":"31","year":"2011","journal-title":"Life Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.addr.2006.10.006","article-title":"The role of degradant profiling in active pharmaceutical ingredients and drug products","volume":"59","author":"Alsante","year":"2007","journal-title":"Drug Deliv. Rev."},{"key":"ref_32","first-page":"238","article-title":"Forced degradation studies for drug substances and drug products- scientific and regula-tory considerations","volume":"7","author":"Rawat","year":"2015","journal-title":"J. Pharm. Sci Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.trac.2018.12.007","article-title":"Recent breakthroughs in the stability testing of pharmaceutical compounds","volume":"111","year":"2019","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1093\/chromsci\/bmw119","article-title":"Stability\u2014indicating method and LC\u2013MS-MS characterization of forced degradation products of sofosbuvir","volume":"54","author":"Nebsen","year":"2016","journal-title":"J. Chromatogr. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.molliq.2018.10.053","article-title":"A study of the inclusion complex of bioac-tive thiadiazole derivative with 2-hydroxypropyl-\u03b2-cyclodextrin: Preparation, characterization and physicochem-ical properties","volume":"273","author":"Khovich","year":"2019","journal-title":"J. Mol. Liq."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.molliq.2016.10.009","article-title":"Investigation of inclusion complex of HP-\u03b3-cyclodextrin with ceftazidime","volume":"224","author":"Misiuk","year":"2016","journal-title":"J. Mol. Liq."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3623","DOI":"10.1016\/j.xphs.2021.07.002","article-title":"Stabilization of the Metastable \u03b1\u2013Form of Indomethacin Induced by the Addition of 2-Hydroxypropyl-\u03b2-Cyclodextrin, Causing Supersaturation (Spring) and Its Sustaining Deployment (Parachute)","volume":"110","author":"Shimizu","year":"2021","journal-title":"J. Pharm. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0031-6865(97)00003-4","article-title":"Mechano-chemical formation of indomethacin \u03b2 cyclodextrin inclusion compounds in powder phase roll mixtures","volume":"72","author":"Nozawa","year":"1997","journal-title":"Pharm. Acta Helv."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.ijpharm.2015.01.010","article-title":"Influence of the preparation method on the physicochemical properties of indomethacin and methyl-\u03b2-cyclodextrin complexes","volume":"479","author":"Rudrangi","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Pessine, F.B., Calderini, A., and Alexandrino, G.L. (2012). Cyclodextrin inclusion complexes probed by NMR techniques. Magnetic Resonance Spectroscopy, InTechOpen.","DOI":"10.5772\/32029"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.jpba.2014.05.014","article-title":"Evaluation of the photoprotective effect of \u03b2-cyclodextrin on the emission of volatile degradation products of ranitidine","volume":"98","author":"Wielgomas","year":"2014","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.ijpharm.2003.10.012","article-title":"The physicochemical characteristics and bioavailability of indomethacin from \u03b2-cyclodextrin, hydroxyethyl-\u03b2-cyclodextrin, and hydroxypropyl-\u03b2-cyclodextrin complexes","volume":"270","author":"Jambhekar","year":"2004","journal-title":"Int. J. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.jpba.2005.05.011","article-title":"Inclusion complex of trimethoprim with \u03b2-cyclodextrin","volume":"39","author":"Li","year":"2005","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Bender, M.L., and Komiyama, M. (1978). Cyclodextrin Chemistry, Springer.","DOI":"10.1007\/978-3-642-66842-5"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3447","DOI":"10.1248\/cpb.33.3447","article-title":"Physicochemical characterization of indomethacin polymorphs and the transformation kinetics in ethanol","volume":"33","author":"Kaneniwa","year":"1985","journal-title":"Chem. Pharm. Bull."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0040-6031(01)00665-7","article-title":"Thermal analysis of cyclodextrins and their inclusion compounds","volume":"380","author":"Giordano","year":"2001","journal-title":"Thermochim. Acta"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3924","DOI":"10.1002\/anie.200802947","article-title":"Binding mechanisms in supramolecular complexes","volume":"48","author":"Schneider","year":"2009","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1016\/S0006-3495(96)79415-8","article-title":"Thermodynamics of hydrogen bond and hydrophobic interactions in cyclodextrin complexes","volume":"71","author":"Ross","year":"1996","journal-title":"Biophys. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1021\/ja01176a030","article-title":"The spectrophotometric investigation of the ineteraction of iodine with aromatic hydrocarbons","volume":"71","author":"Benesi","year":"1949","journal-title":"J. Chem. Soc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S1010-6030(96)04488-7","article-title":"Inclusion complexes of some 3H-indoles with cyclodextrins studied through excited state dynamics and steady state absorption and fluorescence spectroscopy","volume":"103","author":"Nigam","year":"1997","journal-title":"J. Photochem. Photobiol. A"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.molliq.2018.05.120","article-title":"Spectroscopic studies of inclusion complexation between ortho derivatives of p-methylamino- benzoate and \u03b1- and \u03b3-cyclodextrins","volume":"265","author":"Baranowska","year":"2018","journal-title":"J. Mol. Liq."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"113921","DOI":"10.1016\/j.molliq.2020.113921","article-title":"Spectro-scopic studies of the excited-state intramolecular proton and electron transfer processes of methyl benzoate deriv-atives in cucurbit[7]uril nanocage","volume":"318","author":"Baranowska","year":"2020","journal-title":"J. Mol. Liq."},{"key":"ref_53","first-page":"113","article-title":"Formation and stability of inorganic complexes in solution","volume":"9","author":"Job","year":"1928","journal-title":"Ann. Chim."},{"key":"ref_54","unstructured":"(2021, September 01). European Pharmacopoeia 9.0, Indomethacin, 01\/2017:0092. Available online: https:\/\/www.edqm.eu\/en\/european-pharmacopoeia-ph-eur-10th-edition."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s10973-018-7941-0","article-title":"Experimental investigation of effects of variation in heating rate, temperature and heat flux on fire properties of a non-charring polymer","volume":"137","author":"Cran","year":"2019","journal-title":"J. Thermal Anal. Calorim."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/24\/7436\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:43:18Z","timestamp":1760168598000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/24\/7436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,8]]},"references-count":55,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["molecules26247436"],"URL":"https:\/\/doi.org\/10.3390\/molecules26247436","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,8]]}}}