CHARACTERISATION OF INCLUSION COMPLEXES BETWEEN BIFONAZOLE AND DIFFERENT CYCLODEXTRINS IN SOLID AND SOLUTION STATE

Authors

  • Hajnal Kelemen University of Medicine and Pharmacy from Tirgu Mureș, Faculty of Pharmacy, Department of Pharmaceutical Chemistry
  • Angella Csillag University of Medicine and Pharmacy from Tirgu Mureș, Faculty of Pharmacy, Department of Pharmaceutical Chemistry
  • Gabriel Hancu University of Medicine and Pharmacy from Tirgu Mureș, Faculty of Pharmacy, Department of Pharmaceutical Chemistry
  • Blanka Székely-Szentmiklósi University of Medicine and Pharmacy from Tirgu Mureș, Faculty of Pharmacy, Department of Pharmaceutical Chemistry
  • Ibolya Fülöp University of Medicine and Pharmacy from Tirgu Mureș, Faculty of Pharmacy, Department of Toxicology and Biopharmacy
  • Erzsébet Varga University of Medicine and Pharmacy from Tirgu Mureș, Faculty of Pharmacy, Department of Pharmacognosie and Phytotherapy
  • Lavinia Grama University of Medicine and Pharmacy from Tirgu Mureș, Faculty of Pharmacy, Department of Department of General and Inorganic chemistry
  • Gábor Orgován Research Group of Drugs of Abuse and Doping Agents,Department of Pharmaceutical Chemistry, HungarianAcademy of Sciences, Semmelweis University

DOI:

https://doi.org/10.20450/mjcce.2017.1031

Keywords:

bifonazole, cyclodextrins, differential scanning calorimetry, Fourier transform infrared spectroscopy, 1H NMR -CD titrations

Abstract

The aim of this study is to confirm the formation of inclusion complexes between bifonazole (BFZ) and different cyclodextrin (CD) derivatives. Bifonazole, an imidazole antifungal derivative,is a very hydrophobic compound, which is a major drawback in obtaining topical pharmaceutical formulations with optimal bioavailability. Cyclodextrins may increase local drug delivery by enhancing the drug release and/or permeation. The binary systems between bifonazole and cyclodextrins were prepared in two molar ratios by physical-mixture methods.The physicochemical properties of these complexes were studied by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR) methods. Results showed favourable molecular interaction between the components, in solid state and in solution. 1H NMR -CD titrations and molecular modelling study showed that the most stable complex was obtained when using γ-CD. The Job’s method and 2D NMR spectroscopy sustain the 2:1 stoichiometry of the BFZ:γ-CD complex.

References

T.E. Lackner,S. P. Clissold, Bifonazole. A Review of its Antimicrobial Activity and Therapeutic Use in Superficial Mycoses, Drugs,38 (2), 204-225 (1989).

D. Berg, K.H. Büchel, M. Plempel, E. Regel, Antimycotic sterol biosynthesisinhibitors, Trends PharmacolSci, 7, 233 – 238 (1986). DOI:10.1016/0165-6147(86)90330-5

H. Petri, H. Tronnier, P. Haas, Investigations into the anti-inflammatory effect ofbifonazole, In: Hay RJ (ed.). Advances in Topical Antifungal Therapy, Springer Verlag, Berlin, 26-31. 1986

L. Hegemann, S.M. Toso, K.I. Lahijani, G.F. Webster, J. Ditto, Direct Interaction of Antifungal Azole-Derivatives with Calmodulin: A Possible Mechanism for TheirTherapeutic Activity, Journal of Investigative Dermatology, 100 (3), 343-346 (1993). DOI:10.1111/1523-1747.ep12470043

A.P. Tiziani,Havard's nursing guide to drugs, Elsevier Health Sciences, (2010).

http://pubchem.ncbi.nlm.nih.gov/compound/2378#section=Computed-Properties

J.T. Lalwani, V.T Thakkar, H.V. Patel, Enhancement of solubility and oral bioavailability of ezetimibe by a novel solid self nano emulsifying drug deliverysystem (SNEDDS), Int. J. Pharm. and Pharm. Sci.,5 (3), 513-522 (2013).

K.S.G. Arulkumaran, J. Padmapreetha, Enhancement of solubility of ezetimibe by liquisolid technique, International Journal of Pharmaceutical Chemistry and Analysis,1(1), 14-38 (2014).

T. Loftsson, D. Duchene, Cyclodextrins and their pharmaceutical applications, International Journal of Pharmaceutics, 329, 1–11 (2007).DOI: 10.1016/j.ijpharm.2006.10.044

T. Loftsson, B. J. Ólafsdóttir, H.Fridriksdottir, S. Jonsdottir, Cyclodextrincomplexation of NSAIDs: physicochemical characteristics, Eur. J. of Pharm. Sci.,1 (2), 95-101(1993).

E. M. Dell Valle, Cyclodextrins and their uses: a review, Process Biochemistry, 39, 1033-1046 (2004). DOI: 10.1016/S0032-9592(03)00258-9

J. Szejtli, TheCyclodextrins and their Applications in Biotechnology, Carbohydrate Polymers, 12, 375-392 (1990).

P.J. Mura, Analytical techniques for characterization of cyclodextrin complexes in the solid state: A review.Journal of pharmaceutical and biomedical analysis,113, 226-238 (2015). DOI:10.1016/j.jpba.2015.01.058

G. Yurtdas, M. Demirel, L. Genc, Inclusion complexes of fluconazole with β-cyclodextrin: physicochemical characterization and in vitro evaluation of its formulation,Journal of Inclusion Phenomena and Macrocyclic Chemistry,70(3-4), 429-435 (2011). DOI: 10.1007/s10847-010-9908-z

C. Trandafirescu, A. Gyeresi, Z. Szabadai, M. Kata, Z. Aigner, Solid-state characterization of bifonazole-beta-cyclodextrinbinary systems. Note I., Farmacia, 62(3), 513-523 (2014)

R. Singh, N. Bharti, J. Madan, S.N. Hiremath, Characterization of cyclodextrin inclusion complexes—a review, J. Pharm. Sci. Technol,2(3), 171-183(2010).

G. Orgován, H. Kelemen, B. Noszál, Protonation and β-cyclodextrin complex formation equilibria of fluconazole, Journal of Inclusion Phenomena and Macrocyclic Chemistry,84 (3-4), 189-196 (2016).DOI: 10.1007/s10847-016-0595-2

J. Li, S. Zhang, Y. Zhou, S. Guan, L. Zhang, Inclusion complexes of fluconazole with β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin in aqueous solution: preparation, characterization and a structural insight, Journal of Inclusion Phenomena and Macrocyclic Chemistry,84 (3-4), 209-217 (2016). DOI: 10.1007/s10847-010-9908-z

G. Popovic, M. Cakar, The effects of β-cyclodextrin and pH on bifonazolehydrosolubility, Journal of the Serbian Chemical Society,69(3), 225-231(2004).

Gupta, H. K. Kar, Solid State Compatibility Studies of Miconazole Using Thermal and Spectroscopic Methods, Advances in Analytical Chemistry,5(3), 51-55 (2015. DOI: 10.5923/j.aac.20150503.01

P. Job, Job’s method of continuous variation,AnnChim,9, 113-120 (1928).

N. Marangoci, M. Mares, M. Silion, A. Fifere, C. Varganici, A. Nicolescu, C. Deleanu, A. Coroaba, M. Pinteala, B.C. Simionescu, Inclusion complex of a new propiconazole derivative with β-cyclodextrin: NMR, ESI–MS and preliminary pharmacological studies, Results in pharma sciences,1 (1), 27-37 (2011). DOI: 10.1016/j.rinphs.2011.07.001

J.Szejtli, Cyclodextrins and their inclusion complexes, AkadémiaiKiadó, Budapest, 1982.

P.J. Hore, Nuclear Magnetic Resonance. Oxford University Press, Oxford, 98-101. 1995.

Facchiano, R. Ragone, Modification of Job’s method for determining thestoichiometry of protein–protein complexes, Analytical Biochemistry, 313, 170–172 (2003).

S.K. Upadhyay, G. Kumar, NMR and molecular modelling studies on the interaction of fluconazole with β-cyclodextrin, Chemistry Central Journal,3 (1), 1. (2009). DOI:10.1186/1752-153X-3-9

S.R. Arsad, H. Maarof, I.W. Wan, H.Y. Aboul-Enein, Theoretical and Molecular Docking Study of Ketoconazole on Heptakis (2, 3, 6-tri-O-methyl)-β-cyclodextrin as Chiral Selector, Chirality,28 (3), 209-214 (2016). DOI:10.1002/chir.22554

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Published

2017-06-29

How to Cite

Kelemen, H., Csillag, A., Hancu, G., Székely-Szentmiklósi, B., Fülöp, I., Varga, E., Grama, L., & Orgován, G. (2017). CHARACTERISATION OF INCLUSION COMPLEXES BETWEEN BIFONAZOLE AND DIFFERENT CYCLODEXTRINS IN SOLID AND SOLUTION STATE. Macedonian Journal of Chemistry and Chemical Engineering, 36(1), 81–91. https://doi.org/10.20450/mjcce.2017.1031

Issue

Vol. 36 No. 1 (2017)

Section

Analytical Chemistry

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