[en] The inclusion of miconazole into cyclodextrin cavity has been demonstrated by different authors. Preliminary studies have shown which fragment of the molecule is involved in the inclusion. In the present study, AM1 approximate molecular orbital calculations have been performed on several cyclodextrins complexes ( CD, HP CD and HP CD) with miconazole and acidic compounds (maleic, fumaric and L-tartaric acids) as partners.
For all the binary complexes, the inclusion of the dichlorobenzene–CH2–O-group leads to the most stable complex. For the ternary complexes, depending on their conformation and/or their structures, the acids can either stabilize or destabilize the complex. All the theoretical results were in good agreement with experimental data of miconazole inclusion yields into cyclodextrins. This work clearly demonstrates that the structure of both cyclodextrin and acid plays a key-role in the formation of inclusion complexes.
Amato M.E., Djedaini F., Pappalardo G.C., Perly B., and Scarlata G. Molecular modeling of β-cyclodextrin complexes with nootropic drugs. J. Pharm. Sci. 81 (1992) 1157-1161
Barillaro V., Bertholet P., Henry de Hassonville S., Ziémons E., Evrard B., Delattre L., and Piel G. Effect of acidic ternary compounds on the formation of miconazole/cyclodextrin inclusion complexes by means of supercritical carbon dioxide. J. Pharm. Pharm. Sci. 7 (2004) 378-388
Barillaro V., Evrard B., Delattre L., and Piel G. Oral bioavailability in pigs of a miconazole/hydroxypropyl-γ-cyclodextrin/L-tartaric acid inclusion complex produced by supercritical carbon dioxide processing. AAPS J. 7 (2005) (article 16)
Dewar M.J.S., Zoebisch E.G., Healy E.F., and Stewart J.J.P. AM1: a new general purpose quantum mechanical molecular model. J. Am. Chem. Soc. 107 (1985) 3902-3909
Frisch M.J., Trucks G.W., Schlegel H.B., Scuseria G.E., Robb M.A., Cheeseman J.R., Zakrzewski V.G., Montgomery J.A., Stratmann R.E., Burant J.C., Dapprich S., Millam J.M., Daniels A.D., Kudin K.N., Strain M.C., Chen W., Farkas O., Tomasi J., Barone V., Cossi M., Cammi R., Mennucci B., Pomelli C., Adamo C., Clifford S., Ochterski J., Petersson G.A., Ayala P.Y., Cui Q., Morokuma K., Malick D.K., Rabuck A.D., Raghavachari K., Foresman J.B., Ciolowski J., Oritz J.V., Baboul A.G.G., Stefanov B.B., Liu G., Liashenko A., Piskorz P., Komaromi I., Gomperts R., Martin R.L., Fox D.J., Keith T., Al-Laham M.A., Peng C.Y., Nanyakkara A., Gonzalez C., Challacombe M., Gill P.M.W., Jonhson B., Wong M.W., Andres J.L., Head-Gordon M., Replogle E.S., and Pople J.A. Gaussian 98 (1998) A.7
Harata K. The structure of the cyclodextrin complex 20. Crystal-structure of uncomplexed hydrated γ-cyclodextrin. Bull. Chem. Soc. Jpn. 60 (1987) 2763-2767
Lipkowitz K.B. Applications of computational chemistry to the study of cyclodextrins. Chem. Rev. 98 (1998) 1829-1873
Loftsson T., and Brewster M.E. Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J. Pharm. Sci. 85 (1996) 1017-1025
MC Quarrie D.A. Statistical Thermodynamics (1973), Harper & Row, New York
Mura P., Bettinetti G., Melani F., and Manderioli A. Interaction between naproxen and chemically modified β-cyclodextrins in the liquid and solid state. Eur. J. Pharm. Sci. 3 (1995) 347-355
Mura P., Liguori A., Bramanti G., Bettinetti G.P., Campisi E., and Faggi E. Improvement of dissolution properties and microbiological activity of miconazole and econazole by cyclodextrin complexation. Eur. J. Pharm. Biopharm. 38 (1992) 119-123
Piel G., Dive G., Evrard B., Van Hees T., Henry de Hassonville S., and Delattre L. Molecular modeling study of β- and γ-cyclodextrin complexes with miconazole. Eur. J. Pharm. Sci. 13 (2001) 271-279
Piel G., Evrard B., Fillet M., Llabres G., and Delattre L. Development of a non-surfactant parenteral formulation of miconazole by the use of cyclodextrins. Int. J. Pharm. 169 (1998) 15-22
Redenti E., Szente L., and Szejtli J. Drug/cyclodextrin/hydroxy acid multicomponent systems. Properties and pharmaceutical applications. J. Pharm. Sci. 89 (2000) 1-8
Steiner T., and Koellner G. Crystalline β-cyclodextrin hydrate at various humidities: fast, continuous and reversible dehydration studied by X-ray diffraction. J. Am. Chem. Soc. 116 (1994) 5122-5128
Tenjarla S., Puranajoti P., Kasina R., and Mandal T. Preparation, characterisation, and evaluation of miconazole-cyclodextrin complexes for improved oral and topical delivery. J. Pharm. Sci. 87 (1998) 425-429
Van Hees T., Piel G., Henry de Hassonville S., Evrard B., and Delattre L. Determination of the free/included piroxicam ratio in cyclodextrin complexes: comparison between UV spectroscopy and differential scanning calorimetry. Eur. J. Pharm. Sci. 15 (2002) 347-353
Zia V., Rajewski R.A., and Stella V.J. Effect of cyclodextrin charge on complexation of neutral and charged substrates: comparison of (SBE)7M-βCD to HP-β-CD. Pharm. Res. 18 (2001) 667-673
