Influence of polyethylene glycol chain length on compatibility and release characteristics of ternary solid dispersions of itraconazole in polyethylene glycol/hydroxypropylmethylcellulose 2910 E5 blends.
The present study aims to elucidate the influence of the polyethylene glycol chain length on the miscibility of PEG/HPMC 2910 E5 polymer blends, the influence of polymer compatibility on the degree of molecular dispersion of itraconazole, and in vitro dissolution. PEG 2000, 6000, 10,000 and 20,000 were included in the study. Solid dispersions were prepared by spray drying and characterized with MDSC, XRPD and in vitro dissolution testing. The polymer miscibility increased with decreasing chain length due to a decrease in the Gibbs free energy of mixing. Recrystallization of itraconazole occurred as soon as a critical temperature of ca. 75 degrees C was reached for the glass transition that represents the ternary amorphous phase. Due to the lower miscibility degree between the longer PEG types and HPMC 2910 E5, the ternary amorphous phase was further separated, leading to a more rapid decrease of the ternary amorphous phase glass transition as a function of PEG and itraconazole weight percentage and hence, itraconazole recrystallization. In terms of release, an advantage of the shorter chain length PEG types (2000, 6000) over the longer chain length PEG types (10,000, 20,000) was observed for the polymer blends with 5% of PEG with respect to the binary itraconazole/HPMC 2910 E5 solid dispersion. Among the formulations with a 15/85 (w/w) PEG/HPMC 2910 E5 ratio on the other hand, there was no difference in the release profile.
Janssens
Sandrien
S
Laboratorium voor Farmacotechnologie en Biofarmacie, University of Leuven, Herestraat 49 b921, Leuven, Belgium.
Denivelle
Samgar
S
Rombaut
Patrick
P
Van den Mooter
Guy
G
D000935:Antifungal Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D065347:Hypromellose Derivatives; D017964:Itraconazole / Q000737:chemistry*; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008956:Models, Chemical; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D044366:Transition Temperature
D000935:Antifungal Agents; D017964:Itraconazole; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D008747:Methylcellulose