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 three different crystal modifications. It was shown that itraconazole decreased the formation of the polymer modifications with melting transitions at 56 and 59 degrees C but promoted the formation of the modification with a melting transition at 63 degrees 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 degrees 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 degrees 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.
Wang
Xin
X
Laboratorium voor Farmacotechnologie en Biofarmacie, Faculteit Farmaceutische Wetenschappen, K.U. Leuven, Campus Gasthuisberg O+N, Herestraat 49, Leuven 3000, Belgium.
Michoel
Armand
A
Van den Mooter
Guy
G
D000935:Antifungal Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D005079:Excipients / Q000737:chemistry*; D017964:Itraconazole / Q000737:chemistry*; D008752:Methylene Chloride / Q000737:chemistry; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013696:Temperature
D000935:Antifungal Agents; D005079:Excipients; D012997:Solvents; D017964:Itraconazole; D011092:Polyethylene Glycols; D008752:Methylene Chloride