Study of the phase behavior of polyethylene glycol 6000–itraconazole solid dispersions using DSC

The aim of the present study was to investigate the phase behavior of solid dispersions made up of PEG 6000 and itraconazole using DSC. Solid dispersions were prepared by solvent evaporation. DSC analysis of pure PEG 6000 showed three endothermic events, representing the melting transitions of the t...

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Bibliographic Details
Published in:International journal of pharmaceutics 2004-03, Vol.272 (1), p.181-187
Main Authors: Wang, Xin, Michoel, Armand, Van den Mooter, Guy
Format: Article
Language:English
Subjects:
Antifungal Agents - chemistry
Biological and medical sciences
Calorimetry, Differential Scanning - methods
Chemistry, Pharmaceutical
Crystallization
Differential scanning calorimetry (DSC)
Excipients - chemistry
General pharmacology
Itraconazole
Itraconazole - chemistry
Medical sciences
Methylene Chloride - chemistry
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Phase separation
Phase Transition
Polyethylene glycol 6000
Polyethylene Glycols - chemistry
Solubility
Solvents - chemistry
Temperature
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Summary:The aim of the present study was to investigate the phase behavior of solid dispersions made up of PEG 6000 and itraconazole using DSC. Solid dispersions were prepared by solvent evaporation. DSC analysis of pure PEG 6000 showed three endothermic events, representing the melting transitions of the three different crystal modifications. It was shown that itraconazole decreased the formation of the polymer modifications with melting transitions at 56 and 59 °C but promoted the formation of the modification with a melting transition at 63 °C. All dispersions investigated showed the presence of crystalline itraconazole indicating that the drug is not molecularly dispersed in the polymer matrix. However, the presence of an endothermic peak in DSC curves of all solid dispersions at approximately 85–90 °C showed that at least a second phase of pure itraconazole is present also: glassy itraconazole. The protective effect of the polymer is clear at low concentration of drug since no recrystallisation exotherm can be detected. However, at drug concentrations at or above 80%, a recrystallization exotherm at approximately 117 °C can be detected. At least three different phases can be distinguished at room temperature: a polymer phase, crystalline itraconazole and glassy itraconazole. The findings of the present study thus demonstrate the coexistence of multiple drug phases in a solid dispersion.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2003.11.026