Overview of cyclodextrins and medicinal products containing cyclodextrins currently registered in Poland

Ewa Napiórkowska

doi:10.56782/pps.161

Authors

Ewa Napiórkowska Department of Organic and Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw

DOI:

https://doi.org/10.56782/pps.161

Keywords:

cyclodextrins, drugs, excipients, solubility, complexes

Abstract

Cyclodextrins are cyclic oligosaccharides with a unique ability to form non-covalent host-guest complexes with various hydrophobic molecules, including drugs. Consequently, they can improve the solubility and stability of guest molecules. The wide application of cyclodextrins and their derivatives, including in foods, cosmetics, and pharmaceutical sciences, demonstrates their adaptability. Understanding the potential of cyclodextrins in pharmaceutical sciences creates new opportunities for improving the physicochemical properties of drugs and creation of new formulations, design of drug delivery systems and developing innovative treatment strategies. The aim of this work was to gather important information about cyclodextrins including their structure, formation of inclusion complex, application in the pharmaceutical industry and aspects related to the safety of usage of cyclodextrins. The study also provides examples of medicinal products containing cyclodextrins registered in Poland with their indications for use and pharmaceutical forms. The variety of available medicinal products emphasizes the potential of using cyclodextrin in the design of new drugs.

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References

Thakur, S.S.; Parekh, H.S.; Schwable, C.H.; Gan, Y.; Ouyang, D. Solubilization of Poorly Soluble Drugs. In Computational Pharmaceutics, 1st ed.; Ouyang, D., Smith, S.C., Eds,; John Wiley & Sons, Ltd: Chichester, UK, 2015; pp. 31–51. DOI: https://doi.org/10.1002/9781118573983.ch3

Fenyvesi, É.; Vikmon, M.; Szente, L. Cyclodextrins in Food Technology and Human Nutrition: Benefits and Limitations. Crit. Rev. Food Sci. Nutr. 2016, 56, 1981–2004, doi:10.1080/10408398.2013.809513. DOI: https://doi.org/10.1080/10408398.2013.809513

Ferreira, L.; Mascarenhas-Melo, F.; Rabaça, S.; Mathur, A.; Sharma, A.; Giram, P.S.; Pawar, K.D.; Rahdar, A.; Raza, F.; Veiga, F.; et al. Cyclodextrin-Based Dermatological Formulations: Dermo-pharmaceutical and Cosmetic Applications. Colloids Surf. B Biointerfaces 2023, 221, 113012, doi:10.1016/j.colsurfb.2022.113012. DOI: https://doi.org/10.1016/j.colsurfb.2022.113012

Crini, G. Review: A History of Cyclodextrins. Chem. Rev. 2014, 114, 10940–10975, doi:10.1021/cr500081p. DOI: https://doi.org/10.1021/cr500081p

Duchêne, D.; Bochot, A. Thirty Years with Cyclodextrins. Int. J. Pharm. 2016, 514, 58–72, doi:10.1016/j.ijpharm.2016.07.030. DOI: https://doi.org/10.1016/j.ijpharm.2016.07.030

Loftsson, T.; Brewster, M.E. Pharmaceutical Applications of Cyclodextrins: Basic Science and Product Development. J. Pharm. Pharmacol. 2010, 62, 1607–1621, doi:10.1111/j.2042-7158.2010.01030.x. DOI: https://doi.org/10.1111/j.2042-7158.2010.01030.x

Wang, W.; Ouyang, D. Prediction of Free Drug Absorption in Cyclodextrin Formulation by a Modified Physiologically Based Pharmacokinetic Model and Phase Solubility 3-D Surface Graph. Pharm. Res. 2021, 38, 1157–1168, doi:10.1007/s11095-021-03071-3. DOI: https://doi.org/10.1007/s11095-021-03071-3

Saokham, P.; Muankaew, C.; Jansook, P.; Loftsson, T. Solubility of Cyclodextrins and Drug/Cyclodextrin Complexes. Molecules 2018, 23, 1161, doi:10.3390/molecules23051161. DOI: https://doi.org/10.3390/molecules23051161

2D Structure Image of Beta-Cyclodextrin Available online: https://pubchem.ncbi.nlm.nih.gov/compound/444041#section=2D-Structure&fullscreen=true (accessed 2023-July-26)

Kurkov, S. V.; Loftsson, T. Cyclodextrins. Int. J. Pharm. 2013, 453, 167–180, doi:10.1016/j.ijpharm.2012.06.055. DOI: https://doi.org/10.1016/j.ijpharm.2012.06.055

Morin-Crini, N.; Fourmentin, S.; Fenyvesi, É.; Lichtfouse, E.; Torri, G.; Fourmentin, M.; Crini, G. 130 Years of Cyclodextrin Discovery for Health, Food, Agriculture, and the Industry: A Review. Environ. Chem. Lett. 2021, 19, 2581–2617, doi:10.1007/s10311-020-01156-w. DOI: https://doi.org/10.1007/s10311-020-01156-w

Lachowicz, M.; Stańczak, A.; Kołodziejczyk, M. Characteristic of Cyclodextrins: Their Role and Use in the Pharmaceutical Technology. Curr. Drug Targets 2020, 21, 1495–1510, doi:10.2174/1389450121666200615150039. DOI: https://doi.org/10.2174/1389450121666200615150039

Jansook, P.; Ogawa, N.; Loftsson, T. Cyclodextrins: Structure, Physicochemical Properties and Pharmaceutical Applications. Int. J. Pharm. 2018, 535, 272–284, doi:10.1016/j.ijpharm.2017.11.018. DOI: https://doi.org/10.1016/j.ijpharm.2017.11.018

Assaf, K.I.; Gabel, D.; Zimmermann, W.; Nau, W.M. High-Affinity Host–Guest Chemistry of Large-Ring Cyclodextrins. Org. Biomol. Chem. 2016, 14, 7702–7706, doi:10.1039/C6OB01161F. DOI: https://doi.org/10.1039/C6OB01161F

Sonnendecker, C.; Thürmann, S.; Przybylski, C.; Zitzmann, F.D.; Heinke, N.; Krauke, Y.; Monks, K.; Robitzki, A.A.; Belder, D.; Zimmermann, W. Large‐Ring Cyclodextrins as Chiral Selectors for Enantiomeric Pharmaceuticals. Angew. Chem. Int. Ed. 2019, 58, 6411–6414, doi:10.1002/anie.201900911. DOI: https://doi.org/10.1002/anie.201900911

Poulson, B.G.; Alsulami, Q.A.; Sharfalddin, A.; El Agammy, Emam.F.; Mouffouk, F.; Emwas, A.-H.; Jaremko, L.; Jaremko, M. Cyclodextrins: Structural, Chemical, and Physical Properties, and Applications. Polysaccharides 2021, 3, 1–31, doi:10.3390/polysaccharides3010001. DOI: https://doi.org/10.3390/polysaccharides3010001

Jambhekar, S.S.; Breen, P. Cyclodextrins in Pharmaceutical Formulations I: Structure and Physicochemical Properties, Formation of Complexes, and Types of Complex. Drug Discov. Today 2016, 21, 356–362, doi:10.1016/j.drudis.2015.11.017. DOI: https://doi.org/10.1016/j.drudis.2015.11.017

Aiassa, V.; Garnero, C.; Longhi, M.R.; Zoppi, A. Cyclodextrin Multicomponent Complexes: Pharmaceutical Applications. Pharmaceutics 2021, 13, 1099, doi:10.3390/pharmaceutics13071099. DOI: https://doi.org/10.3390/pharmaceutics13071099

Loftsson, T.; Duchene, D. Cyclodextrins and Their Pharmaceutical Applications. Int. J. Pharm. 2007, 329, 1–11, doi:10.1016/j.ijpharm.2006.10.044. DOI: https://doi.org/10.1016/j.ijpharm.2006.10.044

Brewster, M.E.; Loftsson, T. Cyclodextrins as Pharmaceutical Solubilizers. Adv. Drug Deliv. Rev. 2007, 59, 645–666, doi:10.1016/j.addr.2007.05.012. DOI: https://doi.org/10.1016/j.addr.2007.05.012

Salunke, S.; O’Brien, F.; Cheng Thiam Tan, D.; Harris, D.; Math, M.-C.; Ariën, T.; Klein, S.; Timpe, C. Oral Drug Delivery Strategies for Development of Poorly Water Soluble Drugs in Paediatric Patient Population. Adv. Drug Deliv. Rev. 2022, 190, 114507, doi:10.1016/j.addr.2022.114507. DOI: https://doi.org/10.1016/j.addr.2022.114507

Coelho, M.M.; Fernandes, C.; Remião, F.; Tiritan, M.E. Enantioselectivity in Drug Pharmacokinetics and Toxicity: Pharmacological Relevance and Analytical Methods. Molecules 2021, 26, 3113, doi:10.3390/molecules26113113. DOI: https://doi.org/10.3390/molecules26113113

Shahgaldian, P.; Pieles, U. Cyclodextrin Derivatives as Chiral Supramolecular Receptors for Enantioselective Sensing. Sensors 2006, 6, 593–615, doi:10.3390/s6060593. DOI: https://doi.org/10.3390/s6060593

Terashima, H.; Yamamoto, A.; Aizawa, S.; Taga, A.; Mikami, I.; Ishihara, Y.; Kodama, S. Enantioseparation of Phenethylamines by Using High‐performance Liquid Chromatography Column Permanently Coated with Methylated Β‐cyclodextrin. J. Sep. Sci. 2021, 44, 2932–2940, doi:10.1002/jssc.202100343. DOI: https://doi.org/10.1002/jssc.202100343

Chankvetadze, B. The Application of Cyclodextrins for Enantioseparations. In Cyclodextrins and Their Complexes; Dodziuk, H., Ed.: John Wiley & Sons, Ltd, 2006; pp. 119–146. DOI: https://doi.org/10.1002/3527608982.ch6

Higashi, K.; Tozuka, Y.; Moribe, K.; Yamamoto, K. Salicylic Acid/γ-Cydodextrin 2:1 and 4:1 Complex Formation by Sealed-Heating Method. J. Pharm. Sci. 2010, 99, 4192–4200, doi:10.1002/jps.22133. DOI: https://doi.org/10.1002/jps.22133

Mura, P. Analytical Techniques for Characterization of Cyclodextrin Complexes in the Solid State: A Review. J. Pharm. Biomed. Anal. 2015, 113, 226–238, doi:10.1016/j.jpba.2015.01.058. DOI: https://doi.org/10.1016/j.jpba.2015.01.058

Mazurek, A.H.; Szeleszczuk, Ł.; Gubica, T. Application of Molecular Dynamics Simulations in the Analysis of Cyclodextrin Complexes. Int. J. Mol. Sci. 2021, 22, 9422, doi:10.3390/ijms22179422. DOI: https://doi.org/10.3390/ijms22179422

Zhao, Q.; Ye, Z.; Su, Y.; Ouyang, D. Predicting Complexation Performance between Cyclodextrins and Guest Molecules by Integrated Machine Learning and Molecular Modeling Techniques. Acta Pharm. Sin. B 2019, 9, 1241–1252, doi:10.1016/j.apsb.2019.04.004. DOI: https://doi.org/10.1016/j.apsb.2019.04.004

Mortensen, A.; Aguilar, F.; Crebelli, R.; Di Domenico, A.; Dusemund, B.; Frutos, M.J.; Galtier, P.; Gott, D.; Gundert‐Remy, U.; Leblanc, J.; et al. Re‐evaluation of Β‐cyclodextrin (E 459) as a Food Additive. EFSA J. 2016, 14, e04628, doi:10.2903/j.efsa.2016.4628. DOI: https://doi.org/10.2903/j.efsa.2016.4628

European Medicines Agency Annex to the European Commission Guideline on “Excipients in the Labelling and Package Leaflet of Medicinal Products for Human Use” (SANTE-2017-11668) Excipients and Information for the Package Leaflet; 2019; Available online: https://www.ema.europa.eu/en/annex-european-commission-guideline-excipients-labelling-package-leaflet-medicinal-products-human#current-version-section (accessed 2023-July-28)

Sharma, N.; Baldi, A. Exploring Versatile Applications of Cyclodextrins: An Overview. Drug Deliv. 2016, 23, 729–747, doi:10.3109/10717544.2014.938839. DOI: https://doi.org/10.3109/10717544.2014.938839

Carrier, R.L.; Miller, L.A.; Ahmed, I. The Utility of Cyclodextrins for Enhancing Oral Bioavailability. J. Control. Release 2007, 123, 78–99, doi: 10.1016/j.jconrel.2007.07.018. DOI: https://doi.org/10.1016/j.jconrel.2007.07.018

European Medicines Agency Questions and Answers on Cyclodextrins as Excipients in Medicinal Products for Human Use (EMA/CHMP/495747/2013); 2017; Available online: https://www.ema.europa.eu/en/cyclodextrins (accessed 2023-July-28)

Del Valle, E.M.M. Cyclodextrins and Their Uses: A Review. Process Biochem. 2004, 39, 1033–1046, doi:10.1016/S0032-9592(03)00258-9. DOI: https://doi.org/10.1016/S0032-9592(03)00258-9

Loftsson, T.; Masson, M. Cyclodextrins in Topical Drug Formulations: Theory and Practice. Int. J. Pharm. 2001, 225, 15–30, doi:10.1016/S0378-5173(01)00761-X. DOI: https://doi.org/10.1016/S0378-5173(01)00761-X

Shelley, H.; Babu, R.J. Role of Cyclodextrins in Nanoparticle-Based Drug Delivery Systems. J. Pharm. Sci. 2018, 107, 1741–1753, doi:10.1016/j.xphs.2018.03.021. DOI: https://doi.org/10.1016/j.xphs.2018.03.021

Real, D.A.; Bolaños, K.; Priotti, J.; Yutronic, N.; Kogan, M.J.; Sierpe, R.; Donoso-González, O. Cyclodextrin-Modified Nanomaterials for Drug Delivery: Classification and Advances in Controlled Release and Bioavailability. Pharmaceutics 2021, 13, 2131, doi:10.3390/pharmaceutics13122131. DOI: https://doi.org/10.3390/pharmaceutics13122131

Santos, A.C.; Costa, D.; Ferreira, L.; Guerra, C.; Pereira-Silva, M.; Pereira, I.; Peixoto, D.; Ferreira, N.R.; Veiga, F. Cyclodextrin-Based Delivery Systems for in Vivo-Tested Anticancer Therapies. Drug Deliv. Transl. Res. 2021, 11, 49–71, doi:10.1007/s13346-020-00778-5. DOI: https://doi.org/10.1007/s13346-020-00778-5

Lai, W.-F. Cyclodextrins in Non-Viral Gene Delivery. Biomaterials 2014, 35, 401–411, doi:10.1016/j.biomaterials.2013.09.061. DOI: https://doi.org/10.1016/j.biomaterials.2013.09.061

Kovacs, T.; Nagy, P.; Panyi, G.; Szente, L.; Varga, Z.; Zakany, F. Cyclodextrins: Only Pharmaceutical Excipients or Full-Fledged Drug Candidates? Pharmaceutics 2022, 14, 2559, doi:10.3390/pharmaceutics14122559. DOI: https://doi.org/10.3390/pharmaceutics14122559

Charakterystyka Produktu Leczniczego: Mel. Available online: https://rejestrymedyczne.ezdrowie.gov.pl/rpl/search/public (accessed 2023-July-29)

Charakterystyka Produktu Leczniczego: Polopiryna Gardło Spray. Available online: https://rejestrymedyczne.ezdrowie.gov.pl/rpl/search/public (accessed 2023-July-29)

Charakterystyka Produktu Leczniczego: Strepsils Intensive Direct. Available online: https://rejestrymedyczne.ezdrowie.gov.pl/rpl/search/public (accessed 2023-July-29)

Charakterystyka Produktu Leczniczego: Abilify. Available online: https://ec.europa.eu/health/documents/community-register/2004/200406047847/anx_7847_pl.pdf (accessed 2023-July-29)

Charakterystyka Produktu Leczniczego: Baqsimi. Available online: https://www.ema.europa.eu/en/documents/product-information/baqsimi-epar-product-information_pl.pdf (accessed 2023-July-29)

Charakterystyka Produktu Leczniczego: Briviact. Available online: https://ec.europa.eu/health/documents/community-register/2016/20160114133756/anx_133756_pl.pdf (accessed 2023-July-29)

Charakterystyka Produktu Leczniczego: Flamexin. Available online: https://rejestrymedyczne.ezdrowie.gov.pl/rpl/search/public (accessed 2023-July-29)

Charakterystyka Produktu Leczniczego: Naclof. Available online: https://rejestrymedyczne.ezdrowie.gov.pl/rpl/search/public (accessed 2023-July-29)

Charakterystyka Produktu Leczniczego: Prostavasin 60. Available online: https://rejestrymedyczne.ezdrowie.gov.pl/rpl/search/public (accessed 2023-July-29)

Charakterystyka Produktu Leczniczego: Quofenix. Available online: https://www.ema.europa.eu/en/documents/product-information/quofenix-epar-product-information_pl.pdf (accessed 2023-July-29)

Charakterystyka Produktu Leczniczego: Yasminelle. Available online: https://rejestrymedyczne.ezdrowie.gov.pl/rpl/search/public (accessed 2023-July-29)

Charakterystyka Produktu Leczniczego: Yaz. Available online: https://rejestrymedyczne.ezdrowie.gov.pl/rpl/search/public (accessed 2023-July-29)

Charakterystyka Produktu Leczniczego: Kyprolis. Available online: https://www.ema.europa.eu/en/documents/product-information/kyprolis-epar-product-information_pl.pdf (accessed 2023-July-29)

Charakterystyka Produktu Leczniczego: Prevymis. Available online: https://ec.europa.eu/health/documents/community-register/2018/20180108139609/anx_139609_pl.pdf (accessed 2023-July-29)