Preparation and characterization of fusion processed solid dispersions containing a viscous thermally labile...

The primary aim of the present study was to investigate the ability of hydroxypropyl and methoxyl substituted cellulose ethers to stabilize supersaturated concentrations of itraconazole (ITZ), a poorly water-soluble weak base, after an acid-to-neutral pH transition. A secondary aim of the study was to evaluate the effect of fusion processes on polymer stability and molecular weight. Polymer screening studies showed that stabilization of ITZ supersaturation was related to the molecular weight of the polymer and levels of hydroxypropyl and methoxyl substitution. METHOCEL E50LV (E50LV), which is characterized as having a high melt viscosity, was selected for solid dispersion formulation studies. Hot-melt extrusion processing of E50LV based compositions resulted in high torque loads, low material throughput and polymer degradation. KinetiSol Dispersing, a novel fusion based processing technique, was evaluated as a method to prepare the solid dispersions with reduced levels of polymer degradation. An experimental design revealed that polymer molecular weight was sensitive to shearing forces and high temperatures. However, optimal processing conditions resulted in significantly reduced E50LV degradation relative to HME processing. The technique was effectively utilized to prepare homogenous solid solutions of E50LV and ITZ, characterized as having a single glass transition temperature over a wide range of drug loadings. All prepared compositions provided for a high degree of ITZ supersaturation stabilization.