Influence of the preparation method on the physicochemical properties of econazole-β-cyclodextrin complexes
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Econazole (C18H15Cl3N2O) is one of the common antifungal agents whose poor aqueous solubility restricts its use for the treatment of oropharyngeal candidiasis, which is the first symptom of HIV infection. Therefore, the aim of the current study was to investigate the effect of different preparation methods (i.e. kneading, coevaporation, sealed-heating, and supercritical carbon dioxide (SC CO2)) for obtaining solid inclusion complexes between β-cyclodextrin and econazole. The physico-chemical properties of the different products were characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffractometry (PXRD). For the complexes prepared by the SC CO2 method, the effects of temperature and pressure have also been investigated and related to the solubility of econazole in SC CO2. Results suggested the validity of the SC CO2 method for preparing solid complexes between cyclodextrins and econazole, avoiding the use of organic solvents and problems of their complete removal. Moreover, temperature played a major role in promoting drug-carrier interactions, whereas pressure had limited effects.
KeywordsCyclodextrin Econazole Inclusion complex Supercritical carbon dioxide
The authors are grateful to the Research Affairs at the United Arab Emirates University for the financial support of this project (contract no. 01-02-7-12/04) and to Ali Dowaidar and Baboucarr Jobe for their assistance with analysis of the samples.
- 1.Hughes, W.T., Bartley, D.L., Patterson, G.G., Tufenkeji, H.: Ketoconazole and candidiasis: a controlled study. J. Infect. Dis. 147, 1060–1063 (1983)Google Scholar
- 3.Hay, R.J.: Overview of studies of fluconazole in oropharyngeal candidiasis. Rev. Infect. Dis. 12(suppl. 3), S334–S337 (1990)Google Scholar
- 4.Meunier, F., Aoun, M., Gerard, M.: Therapy of oropharyngeal candidiasis in the immunocompromised host: a randomized double-blind study of fluconazole vs ketoconazole. Rev. Infect. Dis. 12(suppl. 3), S364–S368 (1990)Google Scholar
- 6.Pons, V., Greenspan, D., Lozada-Nur, F., McPhail, L., Gallant, J.E., Tunkel, A., Johnson, C.C., McCarty, J., Panzer, H., Levenstein, M., Barranco, A., Green, S.: Oropharyngeal candidiasis in patients with AIDS: randomized comparison of fluconazole versus nystatin oral suspensions. Clin. Infect. Dis. 24, 1204–1207 (1997)CrossRefGoogle Scholar
- 7.Szejtli, J.: Cyclodextrins in drug formulations: Part II. Pharm. Technol. Int. Aug., 24–38 (1991)Google Scholar
- 8.Duchene, D., Wouessidjewe, D.: Physicochemical characteristics and pharmaceutical uses of cyclodextrin derivatives, Part II. Pharm. Technol. Aug., 22–30 (1990)Google Scholar
- 9.Nambu, N., Kikuchi, K., Kikuchi, T., Takahashi, Y., Ueda, H., Nagai, T.: Influence of inclusion of nonsteroidal antiinflammatory drugs with β-cylcodextrin on the irritation to stomach of rats upon oral administration. Chem. Pharm. Bull. 26(12), 3609–3612 (1978)Google Scholar
- 11.Hostetler, J.S., Hanson, L.H., Stevens, D.A.: Effect of cyclodextrin on the pharmacology of antifungal oral azoles. Antimicrob. Agents Chemother. 36(2), 477–480 (1992)Google Scholar
- 14.Lee, S.Y., Chun, I.K.: Design of new parenteral aqueous formulations of fluconazole by the use of modified cyclodextrins. Yakhak Hoechi. 45(4), 357–365 (2001)Google Scholar
- 23.Fabing, I., Leboeuf, F., Jung, J., Perrut, M.: Method for making very fine particles consisting of a principle inserted in a host-molecule. Patents FR 2 815 540- WO 0232462- EP 1 330 266, 2000Google Scholar
- 31.Kiran, E., Brennecke, J.: Supercritical Fluid Engineering Science, ACS Symposium Series 514. American Chemical Society, Washington, D.C. (1993)Google Scholar