Characterization of solid dispersions of itraconazole and hydroxypropylmethylcellulose prepared by melt extrusion, Part II.
OBJECTIVE
This study was done to elucidate the physical and pharmaceutical properties of itraconazole-HPMC dispersions and the influence of water on the phase separation.


METHODS
Extrudates were prepared using a corotating twin-screw hot-stage extruder with fixed process parameters. Modulated-temperature differential scanning calorimetry (MTDSC) and DSC 111 were used to examine the mixing behavior of itraconazole and the carrier by evaluation of the glass transition region. High temperature diffuse reflectance infrared transform spectroscopy (HT-DRIFT) was performed to reveal interactions between itraconazole and HPMC. Dissolution was performed to investigate the pharmaceutical performance of the dispersions.


RESULTS
Although the dissolution rate of itraconazole significantly increased, we found that the solid dispersions do not form a homogeneous system. A different picture was obtained depending on the way MTDSC analysis was performed, i.e., using open or closed sample pans. Water can evaporate in open pans, which allows itraconazole to interact with HPMC and leads to a partially mixed phase. Analysis in hermetically closed pans revealed a further phase separation as water remains on the sample and impedes the interaction between drug and polymer.


CONCLUSIONS
Solid dispersions of itraconazole and HPMC do not form a homogeneous phase.
Six
Karel
K
Laboratorium voor Farmacotechnologie en Biofarmacie, K.U.Leuven, Leuven, Belgium.
Berghmans
Hugo
H
Leuner
Christian
C
Dressman
Jennifer
J
Van Werde
Kristof
K
Mullens
Jules
J
Benoist
Luc
L
Thimon
Mireille
M
Meublat
Laurent
L
Verreck
Geert
G
Peeters
Jef
J
Brewster
Marcus
M
Van den Mooter
Guy
G
D065347:Hypromellose Derivatives; D017964:Itraconazole / Q000737:chemistry* / Q000378:metabolism; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility / Q000187:drug effects; D013678:Technology, Pharmaceutical / Q000379:methods*
D017964:Itraconazole; D065347:Hypromellose Derivatives; D008747:Methylcellulose