{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:07:16Z","timestamp":1790370436965,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T00:00:00Z","timestamp":1547164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The stability profile of a new 1,4-dihydropyridine derivative (DHP), representative of a series with a hexahydroquinoline ring, was studied to design light-stable liquid formulations. This molecule, named M3, has been shown among the analogs to have a high capacity to block both L- and T-type calcium channels. The ethanol solution of the drug was subjected to a photodegradation test, in accordance with standard rules. The concentrations of the drug and its byproducts were estimated using multivariate curve resolution, applied to the spectral data collected during the test. The improvement of both the photostability and water solubility of M3 was investigated by adding the surfactant polysorbate 20 in a 1:5 ratio to aqueous solutions of the drug. These formulations were exposed to stressing light in containers of bleu polyethylene terephthalate (PET), amber PET, and covered amber PET. The best results were obtained when using the covered amber PET container, reaching a degradation percentage of the drug less than 5% after 12 h under an irradiance power of 450 W\/m2. The stability of the compound was compared to that of nimodipine (NIM) under the same conditions.<\/jats:p>","DOI":"10.3390\/pharmaceutics11010028","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T11:36:42Z","timestamp":1547206602000},"page":"28","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A New Generation of Dihydropyridine Calcium Channel Blockers: Photostabilization of Liquid Formulations Using Nonionic Surfactants"],"prefix":"10.3390","volume":"11","author":[{"given":"Giuseppina","family":"Ioele","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2287-9509","authenticated-orcid":false,"given":"Miyase G\u00f6zde","family":"G\u00fcnd\u00fcz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara 06100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Spatari","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9036-1595","authenticated-orcid":false,"given":"Michele","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6154-4330","authenticated-orcid":false,"given":"Fedora","family":"Grande","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0510-3418","authenticated-orcid":false,"given":"Gaetano","family":"Ragno","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1124\/pr.114.009654","article-title":"The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential","volume":"67","author":"Zamponi","year":"2015","journal-title":"Pharmacol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1002\/jhet.2837","article-title":"Cardiovascular Calcium Channel Blockers: Historical Overview, Development and New Approaches in Design","volume":"54","author":"Drapak","year":"2017","journal-title":"J. Heterocycl. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1111\/bph.13906","article-title":"Recent advances in the development of T-type calcium channel blockers for pain intervention","volume":"175","author":"Snutch","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"475","DOI":"10.4161\/chan.4.6.14106","article-title":"Contributions of T-type calcium channel isoforms to neuronal firing","volume":"4","author":"Cain","year":"2010","journal-title":"Channels"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.bbrc.2004.08.049","article-title":"Special issue: Calcium signaling and disease","volume":"323","author":"Carafoli","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/0165-6147(91)90595-J","article-title":"Molecular diversity of voltage dependent Ca2+ channels","volume":"12","author":"Tsien","year":"1991","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1007\/s00424-013-1376-z","article-title":"Synthesis and Evaluation of 1,4-Dihydropyridine Derivatives with Calcium Channel Blocking Activity","volume":"466","author":"Bladen","year":"2014","journal-title":"Pflugers Arch. Eur. J. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1007\/s00424-014-1566-3","article-title":"1,4-Dihydropyridine derivatives with T-type calcium channel blocking activity attenuate inflammatory and neuropathic pain","volume":"467","author":"Bladen","year":"2015","journal-title":"Pflugers Arch. Eur. J. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejmech.2018.05.032","article-title":"Binding mechanism investigations guiding the synthesis of novel condensed 1,4-dihydropyridine derivatives with L-\/T-type calcium channel blocking activity","volume":"155","author":"Schaller","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1007\/s00424-015-1725-1","article-title":"Analgesic effect of a broad spectrum dihydropyridine inhibitor of voltage gated calcium channels","volume":"467","author":"Gadotti","year":"2015","journal-title":"Pflugers Arch. Eur. J. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.ijpharm.2013.07.075","article-title":"Modelling nifedipine photodegradation, photostability and actinometric properties","volume":"456","author":"Maafi","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1081\/AL-120006669","article-title":"Comparative Evaluation of Analytical Methods for Simultaneous Determination of Nisoldipine and Its Photodegradation Products","volume":"35","author":"Vetuschi","year":"2002","journal-title":"Anal. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3190","DOI":"10.1016\/j.tet.2008.01.104","article-title":"Photochemistry of Hantzsch 1,4-dihydropyridines and pyridines","volume":"64","author":"Fasani","year":"2008","journal-title":"Tetrahedron"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107","DOI":"10.4155\/fmc.15.172","article-title":"Photodegradation studies of 1,4-dihydropyridine compounds by MCR analysis on UV spectral data","volume":"8","author":"Ioele","year":"2016","journal-title":"Future Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.jphotochem.2010.08.019","article-title":"Different photodegradation behavior of barnidipine under natural and forced irradiation","volume":"215","author":"Ioele","year":"2010","journal-title":"J. Photochem. Photobiol. A Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1515\/acph-2017-0026","article-title":"Synthesis and photodegradation studies of analogues of muscle relaxant 1,4-dihydropyridine compounds","volume":"67","author":"Ragno","year":"2017","journal-title":"Acta Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jpba.2005.11.025","article-title":"A critical study on the application of the zero-crossing derivative spectrophotometry to the photodegradation monitoring of lacidipine","volume":"42","author":"Ragno","year":"2006","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1093\/jaoac\/89.6.1538","article-title":"Fractional wavelet analysis for the simultaneous quantitative resolution of lacidipine and its photo-degradation product by continuous wavelet transform and multilinear regression calibration","volume":"89","author":"Ragno","year":"2006","journal-title":"J. AOAC Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0039-9140(02)00526-X","article-title":"Application of a classical least squares regression method to the assay of 1,4-dihydropyridine antihypertensives and their photoproducts","volume":"59","author":"Ragno","year":"2003","journal-title":"Talanta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/0378-5173(94)00399-P","article-title":"Analysis of nimodipine and its photodegradation product by derivative spectrophotometry and gas chromatography","volume":"119","author":"Ragno","year":"1995","journal-title":"Int. J. Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0378-5173(93)90380-X","article-title":"Gaschromatographic and UV derivative determination of Nitrendipine and its photodegradation product","volume":"99","author":"Ragno","year":"1993","journal-title":"Int. J. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1016\/j.talanta.2009.06.009","article-title":"Prediction of photosensitivity of 1,4-dihydropyridine antihypertensives by quantitative structure-property relationship","volume":"79","author":"Ioele","year":"2009","journal-title":"Talanta"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"35","DOI":"10.4155\/fmc.13.187","article-title":"Photostability of barnidipine in combined cyclodextrin-in-liposome matrices","volume":"6","author":"Ioele","year":"2014","journal-title":"Future Med. Chem."},{"key":"ref_24","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_25","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1166\/jnn.2006.407","article-title":"Photostabilization of 1,4-dihidropyridine antihypertensives by incorporation into \u03b2-cyclodextrin and liposomes","volume":"6","author":"Ragno","year":"2006","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.foodchem.2018.07.083","article-title":"Surfactant TWEEN20 provides stabilisation effect on anthocyanins extracted from red grape pomace","volume":"271","author":"Jauregi","year":"2019","journal-title":"Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s00217-017-2973-4","article-title":"Oxidative and physical stability of oil-in-water emulsions prepared with quinoa and amaranth proteins","volume":"244","author":"Kauntola","year":"2018","journal-title":"Eur. Food Res. Technol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1208\/s12249-018-1138-5","article-title":"Solid form of lipid-based self-nanoemulsifying drug delivery systems for minimization of diacerein adverse effects: Development and bioequivalence evaluation in albino rabbits","volume":"19","author":"Naseef","year":"2018","journal-title":"AAPS PharmSciTech"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Szymczyk, K., Szaniawska, M., and Taraba, A. (2018). Micellar parameters of aqueous solutions of tween 20 and 60 at different temperatures: Volumetric and viscometric study. Colloids Int., 2.","DOI":"10.3390\/colloids2030034"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.ijpharm.2016.04.020","article-title":"Photostabilization studies of antihypertensive 1,4-dihydropyridines using polymeric containers","volume":"505","author":"Ioele","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_31","unstructured":"International Conference on Harmonization (2003). Stability Testing of New Drug Substances and Products, IFPMA. ICH Q1A(R2)."},{"key":"ref_32","unstructured":"de Juan, A., Rutan, S.C., Maeder, M., and Tauler, R. (2009). Comprehensive Chemometrics, Elsevier."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1002\/cem.947","article-title":"Analytical solution for determining feasible regions of Self Modeling Curve Resolution (SMCR) method based on computational geometry","volume":"19","author":"Rajko","year":"2005","journal-title":"J. Chemom."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ijpharm.2009.11.003","article-title":"Kinetic studies of nitrofurazone photodegradation by multivariate curve resolution applied to UV-spectral data","volume":"386","author":"Mas","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/dta.276","article-title":"Study of photodegradation kinetics of melatonin by multivariate curve resolution (MCR) with estimation of feasible band boundaries","volume":"5","author":"Tauler","year":"2013","journal-title":"Drug Test. Anal."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.aca.2008.04.044","article-title":"Photodegradation study of decabromodiphenyl ether by UV spectrophotometry and a hybrid hard- and soft-modelling approach","volume":"618","author":"Mas","year":"2008","journal-title":"Anal. Chim. Acta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.chemolab.2018.01.011","article-title":"Investigation of the photodegradation profile of tamoxifen using spectroscopic and chromatographic analysis and multivariate curve resolution","volume":"174","author":"Ioele","year":"2018","journal-title":"Chemom. Intell. Lab. Syst."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.ijpharm.2014.01.030","article-title":"The difficulties for a photolabile drug in topical formulations: The case of diclofenac","volume":"465","author":"Ioele","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_39","first-page":"127","article-title":"Phase solubility techniques","volume":"4","author":"Higuchi","year":"1965","journal-title":"Adv. Anal. Chem. Instrum."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/11\/1\/28\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:25:23Z","timestamp":1760185523000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/11\/1\/28"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,11]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,1]]}},"alternative-id":["pharmaceutics11010028"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics11010028","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,11]]}}}