PHOTODEGRADATION OF 1, 4-DIHYDROPYRIDINE ANTIHYPERTENSIVE DRUGS: AN UPDATED REVIEW
DOI:
https://doi.org/10.22159/ijpps.2018v10i1.22562Keywords:
1, 4-Dihydropyridine drugs, Photodegradation, Phototoxicity, Photostabilization, Stressing testAbstract
1, 4-dihydropyridine calcium channels blockers (DHPs) are the most commonly used antihypertensive drugs. Unfortunately, these compounds have a significant degradability to light. The oxidation to the pyridine derivative represents the first, and in many cases the only, step of the degradation mechanism. The photodegradation process causes the complete loss of pharmacological activity and may trigger the formation of single and superoxide oxygen species, potentially responsible for phototoxic reactions. Several analytical techniques have been proposed for DHP determination in the presence of their photoproducts. Nowadays, DHPs are all marketed in solid formulations, especially tablets, because photodegradation is particularly fast in solution. Various approaches aimed to protect molecular integrity and therapeutic activity of these drugs from the effects of light are currently studied. This review covers the studies over the last years about photodegradation of the DHPs and the approaches to obtain photostable formulations of these drugs.
Downloads
References
Elliott WJ, Ram CVS. Calcium channel blockers. J Clin Hypertens 2011;13:687–9.
St-Onge M, Dube PA, Gosselin S, Guimont C, Godwin J, Archambault PM, et al. Treatment for calcium channel blocker poisoning: a systematic review. Clin Toxicol 2014;52:926–44.
Tamargo J, Ruilope LM. Investigational calcium channel blockers for the treatment of hypertension. Expert Opin Investig Drugs 2016;25:1295–309.
Tocci G, Battistoni A, Passerini J, Musumeci MB, Francia P, Ferrucci A, et al. Calcium channel blockers and hypertension. J Cardiovasc Pharmacol Ther 2015;20:121–30.
Khedkar SA, Auti PB. 1, 4-Dihydropyridines: a class of pharmacologically important molecules. Mini Rev Med Chem 2014;14:282–90.
Coca A, Mazon P, Aranda P, Redon J, Divison JA, MartÃnez J, et al. Role of dihydropyridinic calcium channel blockers in the management of hypertension. Expert Rev Cardiovasc Ther 2013;11:91–105.
Carosati E, Ioan P, Micucci M, Broccatelli F, Cruciani G, Zhorov BS, et al. 1,4-Dihydropyridine scaffold in medicinal chemistry, the story so far and perspectives (part 2): action in other targets and antitargets. Curr Med Chem 2012;19:4306–23.
Maafi W, Maafi M. Modelling nifedipine photodegradation, photostability and actinometric properties. Int J Pharm 2013;456:153–64.
Vetuschi C, Ragno G, Veronico M, Risoli A, Gianandrea A. Comparative evaluation of analytical methods for simultaneous determination of nisoldipine and its photodegradation products. Anal Lett 2002;35:1327–39.
De Filippis P, Bovina E, Da Ros L, Fiori J, Cavrini V. Photodegradation studies on lacidipine in solution: basic experiments with a cis-trans reversible photoequilibrium under UV-A radiation exposure. J Pharm Biomed Anal 2002;27:803–12.
Kawabe Y, Nakamura H, Hino E, Suzuki S. Photochemical stabilities of some dihydropyridine calcium-channel blockers in powdered pharmaceutical tablets. J Pharm Biomed Anal 2008;47:618–24.
Fasani E, Albini A, Mella M. Photochemistry of hantzsch 1,4-dihydropyridines and pyridines. Tetrahedron 2008;64:3190–6.
Ragno G, Vetuschi C, Risoli A, Ioele G. Application of a classical least-squares regression method to the assay of 1,4-dihydropyridine antihypertensives and their photoproducts. Talanta 2003;59:375–82.
Javidnia K, Hemmateenejad B, Miri R, Saeidi-Boroujeni M. Application of a self-modeling curve resolution method for studying the photodegradation kinetics of nitrendipine and felodipine. J Pharm Biomed Anal 2008;46:597-602.
Ioele G, De Luca M, Oliverio F, Ragno G. Prediction of photosensitivity of 1,4-dihydropyridine antihypertensives by quantitative structure-property relationship. Talanta 2009;79: 1418–24.
Ioele G, Gunduz MG, De Luca M, Simsek R, Safak C, Muzzalupo R, et al. Photodegradation studies of 1,4-dihydropyridine compounds by MCR analysis on UV spectral data. Future Med Chem 2016;8:107–15.
Gunduz MG, Ragno G, Simsek R, De Luca M, Safak C, Grande F, et al. Synthesis and photodegradation studies of analogues of muscle relaxant 1,4-dihydropyridine compounds. Acta Pharm 2017;67:341-55.
Zaheer MR, Gupta A, Iqbal J, Zia Q, Ahmad A, Roohi OM, et al. Molecular mechanisms of drug photodegradation and photosensitization. Curr Pharm Des 2016;22:768-82.
Altannak NF. Liquid chromatography-mass spectrometry method to assess naloxone hydrochloride photostability under artificial light and sunlight exposure at room temperature. Asian J Pharm Clin Res 2015;8:290-2.
Kapavarapu S, Mopidevi N, Chintala R. Forced degradation studies and reversed-phase high-performance liquid chromatographic method validation for the determination of ceritinib in bulk and its pharmaceutical dosage form. Asian J Pharm Clin Res 2015;8:44-51.
Naveed S, Uroog S, Waheed N. Degradation studies of different brands of moxifloxac in available in the market. Int J Curr Pharm Res 2015;5:110-6.
Albini A, Fasani E. Drugs photochemistry and photostability, The Royal Society of Chemistry, Cambridge (UK); 1998.
Piechocki JT, Thoma K. Pharmaceutical photostability and stabilization technology. CRC Press: New York; 2006.
Tønnesen HH. Formulation and stability testing of photolabile drugs. Int J Pharm 2001;225:1-14.
Tønnessen HH. Photostability of drugs and drug formulations. CRC Press; 2010. p. 435.
ICH Q1B Guideline Photostability Testing of New Drug Substances and Products Comments for its Application. Fed Regist; 1996. p. 62.
Baertschi SW. A critical assessment of the ICH guideline on photostability testing of new drug substances and products (Q1B): recommendation for revision. J Pharm Sci 2010;99:2934-40.
Baertschi SW, Clapham D, Foti C, Kleinman MH, Kristensen S, Reed RA, et al. Implications of in-use photostability: proposed guidance for photostability testing and labeling to support the administration of photosensitive pharmaceutical products, part 1: drug products administered by injection. J Pharm Sci 2013;2:3888-99.
Baertschi SW, Clapham D, Foti C, Kleinman MH, Kristensen S, Reed RA, et al. Implications of in-use photostability: proposed guidance for photostability testing and labeling to support the administration of photosensitive pharmaceutical products, part 2: topical drug product. J Pharm Sci 2015;104:2688-701.
Fasani E, Albini A, Gemme S. Mechanism of the photochemical degradation of amlodipine. Int J Pharm 2008;352:197–201.
Ragno G, Garofalo A, Vetuschi C. Photodegradation monitoring of amlodipine by derivative spectrophotometry. J Pharm Biomed Anal 2002;27:19–24.
Zhu B, Zonja B, Gonzalez O, Sans C, Perez S, Barcelo D, et al. Degradation kinetics and pathways of three calcium channel blockers under UV irradiation. Water Res 2015;86:9–16.
Jakimska A, Sliwka-Kaszynska M, Nagorski P, Namiesnik J, Kot-Wasik A. Phototransformation of amlodipine: degradation kinetics and identification of its photoproducts. Morishita R Plos One 2014;9:e109206.
Stoiljkovic Z, Jadranin M, Djuric S, Petrovic S, Ivic A, Mijin D. Investigation of forced and total degradation products of amlodipine besylate by liquid chromatography and liquid chromatography-mass spectrometry. Chem Ind Chem Eng Q 2014;20:295–304.
Ohashi K, Ebihara A. Aranidipine (MPC-1304), a new dihydropyridine calcium antagonist: a review of its antihypertensive action. Cardiovasc Drug Rev 1996;14:1–16.
Kuwata M, Tanaka G, Kashihara A, Hasegawa H, Morita K. Single dose toxicity studies of main metabolites and a photo-degradation product of MPC-1304 in mice. Jpn Pharmacol Ther 1993;21:939–45.
Wellington K, Scott LJ. Azelnidipine. Drugs 2003;63:2613-21.
Patel JK, Patel NK. Validated stability-indicating RP-HPLC method for the simultaneous determination of azelnidipine and olmesartan in their combined dosage form. Sci Pharm 2014;82:541–54.
Malhotra HS, Plosker GL. Barnidipine. Drugs 2001;61:989–98.
Ioele G, Oliverio F, Andreu I, De Luca M, Miranda MA, Ragno G. Different photodegradation behavior of barnidipine under natural and forced irradiation. J Photochem Photobiol A 2010;215:205–13.
Ioele G, Luca M De. Assessment of acute toxicity and synergic effect of drugs in water. Bioluminescence Test 2014;39:1190–8.
Cheng ZG, Dai XY, Li LW, Wan Q, Ma X, Xiang GY. Synthesis and characterization of impurities of barnidipine hydrochloride, an antihypertensive drug substance. Molecules 2014;19:1344–52.
Karasaka A. First order derivative spectrophotometric method for the determination of benidipine hydrochloride pharmaceutical preparations and forced degradation study. Opt Spectrosc 2015;118:1002–6.
Kadam A, Hamrapurkar P, Patil S, Manoharan M, Suryagandha A. Development and validation of stability indicating RP-HPLC method for the estimation of cilnidipine in bulk and pharmaceutical dosage form. Int J Pharm Sci Rev Res 2015;30:177–81.
Zhou Y, Zhou F, Yan F, Yang F, Yao Y, Zou Q. Structural analysis and quantitative determination of clevidipine butyrate impurities using an advanced RP-HPLC method. J Chromatogr Sci 2016;54:353-60.
Cardoza RM, Amin PD. A stability indicating LC method for felodipine. J Pharm Biomed Anal 2002;27:711–8.
Pizarro N, Gunther G, Nunez-Vergara LJ. Photophysical and photochemical behavior of nimodipine and felodipine. J Photochem Photobiol A 2007;189:23–9.
Narurkar AN, Sheen PC, Bernstein DF, Augustine MA. Studies on the light stability of flordipine tablets in amber blister packaging material. Drug Dev Ind Pharm 1986;12:1241–7.
Nunez-Vergara LJ, Sunkel C, Squella JA. Photodecomposition of a new 1,4-dihydropyridine: furnidipine. J Pharm Sci 1994;83:502–7.
Mielcarek J, Daczkowska E. Photodegradation of inclusion complexes of isradipine with methyl-β-cyclodextrin. J Pharm Biomed Anal 1999;21:393–8.
Belal F, Elbrashy A, Eid M, Nasr JJ. Stability-indicating LC method for the determination of lacidipine in tablets application to degradation kinetics and content uniformity testing. Chromatographia Vieweg Verlag 2009;69:1201–9.
Dinc E, Ragno G, Baleanu D, De Luca M, Ioele G. Fractional wavelet transform-continous wavelet transform for the quantification of melatonin and its photodegradation product. Spectrosc Lett 2012;45:337-43.
Ragno G, Ioele G, De Luca M, Garofalo A, Grande F, Risoli A. A critical study on the application of the zero-crossing derivative spectrophotometry to the photodegradation monitoring of lacidipine. J Pharm Biomed Anal 2006;42:39–45.
Fiori J, Gotti R, Bertucci C, Cavrini V. Investigation on the photochemical stability of lercanidipine and its determination in tablets by HPLC–UV and LC–ESI–MS/MS. J Pharm Biomed Anal 2006;41:176–81.
Ragno G, Vetuschi C. UV derivative spectrophotometric assay of nicardipine and its photodegradation product. Pharmazie 1998;53:628–31.
Ragno G, Aiello F, Garofalo A, Ioele G, Sinicropi MS. Multivariate least squares regression applied to the spectrophotometric analysis of manidipine and its main photoproduct. Il Farmaco 2003;58:909–15.
Todeschini V, Sangoi M da S, Goelzer GK, Andrade JM de M, Volpato NM. Delapril and manidipine main degradation products: LC-UV and LC-ESI-MS evaluations, decay kinetic, and in vitro cytotoxicity studies. J Liq Chromatogr Relat Technol 2015;38:1333–42.
Bonferoni MC, Mellerio G, Giunchedi P, Caramella C, Conte U. Photostability evaluation of nicardipine HCl solutions. Int J Pharm 1992;80:109–17.
Teraoka R, Otsuka M, Matsuda Y. Evaluation of photostability of solid-state nicardipine hydrochloride polymorphs by using Fourier-transformed reflection–absorption infrared spectroscopy–effect of grinding on the photostability of crystal form. Int J Pharm 2004;286:1-8.
Shamsipur M, Hemmateenejad B, Akhond M, Javidnia K, Miri R. A study of the photo-degradation kinetics of nifedipine by multivariate curve resolution analysis. J Pharm Biomed Anal 2003;31:1013-9.
Dhuna M, Beezer AE, Connor JA, Clapham D, Courtice C, Frost J, et al. LED-array photocalorimetry: Instrument design and application to photostability of nifedipine. J Pharm Biomed Anal 2008;48:1316–20.
Latosinska JN, Latosinska M, Seliger J, Zagar V. An innovative method for the non-destructive identification of photodegradation products in solid state: 1H–14N NMR–NQR and DFT/QTAIM study of photodegradation of nifedipine (anti-hypertensive) to nitrosonifedipine (potential anti-oxidative). Eur J Pharm Sci 2012;47:97–107.
Mielcarek J, Stobiecki M, Frański R. Identification of photodegradation products of nilvadipine using GC-MS. J Pharm Biomed Anal 2000;24:71–9.
Augustyniak W, Mielcarek J, Milewski M, Szamburska O. Spectroscopic and HPLC studies of photodegradation of nilvadipine. Drug Dev Ind Pharm 2001;27:1031–8.
Ragno G, Veronico M, Vetuschi C. Analysis of nimodipine and its photodegradation product by derivative spectrophotometry and gas chromatography. Int J Pharm 1995;119:115–9.
Marinkovic V, Agbaba D, Karljikovic-Rajic K, Comor J, Zivanov-Stakic D. UV derivative spectrophotometric study of the photochemical degradation of nisoldipine. Il Farmaco 2000;55:128–33.
Marinkovic VD, Agbaba D, Karljikovic-Rajic K, Vladimirov S, Nedeljkovic JM. Photochemical degradation of solid-state nisoldipine monitored by HPLC. J Pharm Biomed Anal 2003;32:929–35.
Agbaba D, Vucicevic K, Marinkovic V. Determination of nisoldipine and its impurities in pharmaceuticals. Chromatographia 2004;60:223–7.
Tipre D, Vavia P. Oxidative degradation study of nitrendipine using stability indicating, HPLC, HPTLC and spectro-photometric method. J Pharm Biomed Anal 2001;24:705–14.
Alvarez-Lueje A, Sturm J, Squella JA, Nunez-Vergara LJ. Hydrolytic degradation of nitrendipine and nisoldipine. J Pharm Biomed Anal 2002;28:887–95.
Ragno G, Veronico M, Vetuschi C. Gas chromatographic and UV derivative determination of nitrendipine and its photodegradation product. Int J Pharm 1993;99:351–5.
Cortes M, Cardenas A, Hidalgo M, Glena C, Fernandez E, Sunkel C. New 4-alkyl-1,4-dihydropyridines: evaluation of photostability and phototoxic potential. J Photochem Photobiol B 1993; 19:135–8.
Baranda AB, Alonso RM, Jimenez RM, Weinmann W. Instability of calcium channel antagonists during sample preparation for LC–MS–MS analysis of serum samples. Forensic Sci Int 2006;156:23–34.
Gil-Agustà MT, Carda-Broch S, Ll Monferrer-Pons, Esteve-Romero JS. Photostability studies for micellar liquid chromatographic determination of nifedipine in serum and urine samples. Biomed Chromatogr 2006;20:154–60.
Onoue S, Igarashi N, Yamauchi Y, Murase N, Zhou Y, Kojima T, et al. In vitro phototoxicity of dihydropyridine derivatives: a photochemical and photobiological study. Eur J Pharm Sci 2008;33:262–70.
De Luca M, Ioele G, Spatari C, Ragno G. Photostabilization studies of antihypertensive 1,4-dihydropyridines using polymeric containers. Int J Pharm 2016;505:376–82.
Mielcarek J, Grobelny P, Szamburska P. The effect of β-carotene on the photostability of nisoldipine. Methods Find Exp Clin Pharmacol 2005;27:167–71.
Sharma S, Saraogi GK, Kumar V. Development of spectrophotometric methods for simultaneous determination of artesunate and curcumin in liposomal formulation. Int J Appl Pharm 2015;7:18-21.
Yunus YK, Vasanti S. Liposomes containing phytochemicals for cancer treatment-an update. Int J Curr Pharm Res 2017;9:20-4.
Ragno G, Risoli A, Loele G, Cione E, De Luca M. Photostabilization of 1,4-dihydropyridine antihypertensives by incorporation into β-cyclodextrin and liposomes. J Nanosci Nanotechnol 2006;6:9-10.
Mielcarek J. Studies on inclusion complexes of felodipine with β-cyclodextrin. J Inclusion Phenom Mol Recognit Chem 1998; 30:243–52.
Ragno G, Cione E, Garofalo A, Genchi G, Ioele G, Risoli A, et al. Design and monitoring of photostability systems for amlodipine dosage forms. Int J Pharm 2003;265:125–32.
Jang DJ, Jeong EJ, Lee HM, Kim BC, Lim SJ, Kim CK. Improvement of bioavailability and photostability of amlodipine using redispersible dry emulsion. Eur J Pharm Sci 2006;28:405–11.
Narkhede MR, Kuchekar BS, Nehete JY. Ternary systems of HP β-cyclodextrin felodipine inclusion complexes: preparation, characterization and solubility studies. Res J Pharm Technol 2011;4:1809–15.
Brito J, Pozo A, Garcia C, Nunez-Vergara L, Morales J, Gunther G, et al. Photodegradation of nimodipine and felodipine in microheterogeneous systems. J Chil Chem Soc 2012;57:1313–7.
Ioele G, De Luca M, Ragno G. Photostability of barnidipine in combined cyclodextrin-in-liposome matrices. Future Med Chem 2014;6:35-43.
Himabindu S, Sathish D, Kumar P, Shayeda S. Formulation and ex vivo evaluation of buccal tablets of isradipine in a β-cyclodextrin complex to improve the photostability. Curr Drug Ther 2013;8:121–31.
Park JBB, Lee GHH, Kang JWW, Jeon ISS, Kim JMM, Kim KBB, et al. Improvement of photostability and dissolution profile of isradipine using inclusion complex. J Pharm Investig 2013;43:55–61.
Pomponio R, Gotti R, Fiori J, Cavrini V, Mura P, Cirri M, et al. Photostability studies on nicardipine–cyclodextrin complexes by capillary electrophoresis. J Pharm Biomed Anal 2004;35:267–75.
Tagliari MP, Granada A, Segatto Silva MA, Stulzer HK, Zanetti-Ramos BG, Fernandes D, et al. Development of oral nifedipine-loaded polymeric nanocapsules: physicochemical characterisation, photostability studies, in vitro and in vivo evaluation. Quim Nova 2015;38:781–6.
Fujimoto Y, Hirai N, Takatani-Nakase T, Takahashi K. Photostable solid dispersion of nifedipine by porous calcium silicate. Chem Pharm Bull 2016;64:1218–21.
Shende MA, Markandeeywar T. Photostability studies and development of fast release nifedipine tablets. Int J Pharma Bio Sci 2010;1:1–14.
Published
How to Cite
Issue
Section
