Characterization of Inclusion Complexes between Miconazole and Different Cyclodextrin Derivatives

Kelemen, Hajnal; Hancu, Gabriel; Gâz-Florea, Serban Andrei; Nemes-Nagy, Eniko; Papp, Lajos Attila; Mircia, Eleonora

doi:10.2478/amma-2018-0012

Abstract

Objective: Miconazole, an imidazole antifungal derivative, is a very hydrophobic compound, a major drawback in obtaining topical pharmaceutical formulations with optimal bioavailability. Cyclodextrins (CDs) may increase local drug delivery by enhancing the drug release and/or permeation. The aim of the study is the characterization of inclusion complexes between miconazole and different CD derivatives.

Methods: Several CD derivatives were tested in the experiments. The binary systems between miconazole and different CDs were prepared in 1:1 molar ratios by physical-mixture and kneading methods. Differential scanning calorimetry (DSC) and Fourier transformed-infrared spectroscopy (FT-IR) methods were used to characterize solid state interactions between miconazole and CDs in their binary systems.

Results: The FT-IR analysis suggests the formation of a new solid phase, indicating a molecular interaction between the components. The DSC analysis sustains the hypothesis of formation of partial inclusion complexes between miconazole nitrate and CD.

Conclusion: The thermic behaviour of the complexes depends both on the preparation method and the composition of the products.

References

1. Zirngibl L – Antifungal azoles: a comprehensive survey of their structures and properties. Weinheim: Wiley-VCH; 1998, 85-86.10.1002/3527602682
Search in Google Scholar Back to article
2. Beale Jr. JM – Anti-infective Agents, in Beale Jr. JM, Block JH (eds.): Wilson and Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry. Lippincott William and Wilkins, Philadelphia, 2004, 179-241.
Search in Google Scholar Back to article
3. Sriram B, Agarwal PK, Tee NW et al. – Systemic candidiasis in extremely low birthweight (ELBW) Neonates despite the routine use of topical miconazole prophylaxis: trends, risk factors and outcomes over an 11-year period. Ann Acad Med Singapore, 2014;43(5):255-262.10.47102/annals-acadmedsg.V43N5p255
Search in Google Scholar Back to article
4. Al-Badr AA – Miconazole nitrate: comprehensive profile, Profiles Drug Subst Excip Relat Methodol. 2005;32:3-65.10.1016/S0099-5428(05)32001-6
Search in Google Scholar Back to article
5. Stella VJ, He Q – Cyclodextrins. Exp Toxicol Pathol. 2008;36(1):30-42.10.1177/0192623307310945
Search in Google Scholar Back to article
6. Szejtli J – Cyclodextrin inclusion complexes. In Cyclodextrin technology. Springer, Dordrecht, 1998, 79-185.10.1007/978-94-015-7797-7_2
Search in Google Scholar Back to article
7. Loftsson T, Brewster ME – Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J Pharm Sci. 1996;85(10):1017-1025.10.1021/js950534b
Search in Google Scholar Back to article
8. Szente L, Szejtli J – Highly soluble cyclodextrin derivatives: chemistry, properties, and trends in development. Adv Drug Deliv Rev. 1999;36(1):17-28.10.1016/S0169-409X(98)00092-1
Search in Google Scholar Back to article
9. Loftsson T, Hreinsdóttir D, Másson M – Evaluation of cyclodextrinsolubilization of drugs. Int J Pharm. 2005;302(1-2):18-28.10.1016/j.ijpharm.2005.05.04216099118
Search in Google Scholar Back to article
10. Rai VK, Dwivedi H, Yadav NP et al - Solubility enhancement of miconazole nitrate: binary and ternary mixture approach. Drug Dev Ind Pharm. 2014;40(8):1021-1029.10.3109/03639045.2013.80148723781847
Search in Google Scholar Back to article
11. Höhne G, Hemminger WH,. Flammersheim HJ – Theoretical fundamentals of differential scanning calorimeters. Differential Scanning Calorimetry. Springer, Berlin, Heidelberg, 1996, 21-40.10.1007/978-3-662-03302-9_3
Search in Google Scholar Back to article
12. Mura P, Maestrelli F, Cirri M et al – Differential scanning calorimetry as an analytical tool in the study of drug-cyclodextrin interactions. J Therm Anal Calorim.. 2003;73(2):635-646.10.1023/A:1025494500283
Search in Google Scholar Back to article
13. Yurtdaş G, Demirel M, Genç L – Inclusion complexes of fluconazole with β-cyclodextrin: physicochemical characterization and in vitro evaluation of its formulation. J Incl Phenom Macrocycl Chem. 2011;70(3-4):429-435.10.1007/s10847-010-9908-z
Search in Google Scholar Back to article
14. Kelemen H, Csillag A, Hancu G et al – Characterization of inclusion complexes between bifonazole and different cyclodextrins in solid and solution state. Maced J Chem Chen En. 2017;36(1):81-91.10.20450/mjcce.2017.1031
Search in Google Scholar Back to article
15. Jug M, Mennini N, Kövér KE et al. – Comparative analysis of binary and ternary cyclodextrin complexes with econazole nitrate in solution and in solid state. J Pharm Biomed Anal. 2014;91:81-91.10.1016/j.jpba.2013.12.02924444785
Search in Google Scholar Back to article
16. Ramos JJM, Diogo HP–The slow relaxation dynamics in active pharmaceutical ingredients studied by DSC and TSDC: voriconazole, miconazole and itraconazole. Int J Pharm. 2016;501(1-2): 39-48.10.1016/j.ijpharm.2016.01.05726826567
Search in Google Scholar Back to article
17. Ribeiro A, Figueiras A, Santos D et al – Preparation and solid-state characterization of inclusion complexes formed between miconazole and methyl-β-cyclodextrin.AAPS PharmSciTech. 2008;9(4):1102-1109.10.1208/s12249-008-9143-8262826918975116
Search in Google Scholar Back to article
18. Ziemons E, Bourichi H, Mantanus J et al – Determination of binary polymorphic mixtures of fluconazole using near infrared spectroscopy and X-ray powder diffraction: a comparative study based on the pre-validation stage results. J Pharm Biomed Anal. 2011;55(5):1208-1212.10.1016/j.jpba.2011.02.01921466938
Search in Google Scholar Back to article
19. Orgován G, Kelemen H, Noszál B – Protonation and β-cyclodextrin complex formation equilibria of fluconazole. J Incl Phenom Macrocycl Chem. 2016;84(3-4):189-196.10.1007/s10847-016-0595-2
Search in Google Scholar Back to article
20. Wang JH, Cai Z – Investigation of inclusion complex of miconazole nitrate with β-cyclodextrin. Carbohydrate polymers. 2008;72(2): 255-260.10.1016/j.carbpol.2007.08.009
Search in Google Scholar Back to article
21. Gupta HKK – Solid state compatibility studies of miconazole using thermal and spectroscopic methods. Adv Anal Chem. 2015;5(3):51-55.
Search in Google Scholar Back to article
22. Barillaro V, Dive G, Ziémons et al. – Theoretical and experimental vibrational study of miconazole and its dimers with organic acids: Application to the IR characterization of its inclusion complexes with cyclodextrins. . Int J Pharm. 2008;350(1-2):155-165.10.1016/j.ijpharm.2007.08.04817933475
Search in Google Scholar Back to article
23. Trandafirescu C, GyéresiÁ, Szabadai Z et al. – Solid-state characterization of bifonazole-betacyclodextrin binary systems. Note I. Farmacia. 2014;62(3):513-523.
Search in Google Scholar Back to article

Characterization of Inclusion Complexes between Miconazole and Different Cyclodextrin Derivatives

Abstract

Paradigm

My account