Physicochemical properties of antifungal drug–cyclodextrin complexes prepared by supercritical carbon dioxide and by conventional techniques

• Published in: Journal of pharmaceutical and biomedical analysis 2009-02, Vol.49 (2), p.227-233
• Main Authors: Al-Marzouqi, Ali H., Elwy, Hanan M., Shehadi, Ihsan, Adem, Abdu
• Format: Article
• Language: English
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Antifungal Agents - chemistry; Atmospheric Pressure; Biological and medical sciences; Calorimetry, Differential Scanning; Carbon Dioxide - chemistry; Chemical Phenomena; Cyclodextrins - chemistry; Econazole; Econazole - chemistry; Fluconazole; Fluconazole - chemistry; Fundamental and applied biological sciences. Psychology; General pharmacology; Human immunodeficiency virus; Itraconazole; Itraconazole - chemistry; Medical sciences; Molecular Structure; Pharmacology. Drug treatments; Powders; Solubility; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Supercritical CO 2; Technology, Pharmaceutical - methods; Temperature; X-Ray Diffraction; β-Cyclodextrin
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2008.10.032

Antifungal drugs are the most common systemic drugs used for the treatment of oropharyngeal candidiasis, which is the first symptom of HIV infection. However, the efficacy and bioavailability of these drugs have been limited by their poor aqueous solubility and dissolution rate. Therefore, the aim of this study was to investigate the effect of different preparation methods (i.e. kneading, coevaporation, sealed-heating, and a solid inclusion technique using supercritical carbon dioxide carrier (SC CO 2-inclusion)) for obtaining solid inclusion complexes between β-cyclodextrin and three antifungal drugs (itraconazole, econazole, and fluconazole). The physicochemical 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 CO 2-inclusion method, the effects of temperature and pressure have also been investigated. Results suggested the possibility of complex formation between β-cyclodextrin and the three antifungal agents, and indicated that inclusion formation was influenced by the preparation technique. SC CO 2-inclusion method proved to be an effective technique for preparing solid-state inclusion complexes between β-cyclodextrin and antifungal drugs, avoiding the use of organic solvents. Moreover, temperature of the SC CO 2 played a major role in promoting drug–carrier interactions, whereas pressure had limited effects.