Identification of phase separation in solid dispersions of itraconazole and Eudragit E100 using microthermal analysis.
OBJECTIVE
To evaluate the phase separation in itraconazole/Eudragit E100 solid dispersions prepared by hot-stage extrusion.


METHODS
Extrudates were prepared using a corotating twin-screw extruder at 180 degrees C. Micro-TA was used to evaluate the phase separation, where the AFM mode is used to visualize the different phases and local thermal analysis (LTA) to characterize the different phases


RESULTS
Itraconazole formed a homogeneous mixture with Eudragit E100 with drug concentrations up to approximately 20%. Above this concentration, phase separation was observed. MTDSC revealed two Tgs and the mesophase of free glassy itraconazole. Performing micro-TA on the surface of these dispersions indicated an increase in sample roughness in the z-axis piezo signal, which could be an indication of free glassy itraconazole. However, thermal conductivity did not reveal differences between separate phases. Performing LTA, where only a small area (20 x 20 microm) is heated, showed two separate and mixed phases of itraconazole and Eudragit E100. Tip penetration in itraconazole and Eudragit E100 occurred at 332K and 383K respectively. The difference in tip penetration was explained in terms of the difference in fragility.


CONCLUSIONS
Micro-TA makes it possible to characterize separate phases of itraconazole and Eudragit E100, thereby confirming the MTDSC results on phase separation.
Six
Karel
K
Laboratorium voor Farmacotechnologie en Biofarmacie, K. U. Leuven, B3000 Leuven, Belgium.
Murphy
John
J
Weuts
Ilse
I
Craig
Duncan Q M
DQ
Verreck
Geert
G
Peeters
Jef
J
Brewster
Marcus
M
Van den Mooter
Guy
G
D004055:Differential Thermal Analysis / Q000379:methods; D017964:Itraconazole / Q000032:analysis* / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000032:analysis* / Q000737:chemistry
D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D017964:Itraconazole