Impact of Crystal Structure and Polymer Excipients on the Melt Crystallization Kinetics of Itraconazole Polymorphs

The crystal structure of itraconazole (ITZ) Form II has been determined by single-crystal X-ray diffraction, and the effects of crystal structure and two polymer excipients, Kollidone VA64 (PVPVA64) and hydroxypropylmethyl cellulose acetate succinate (HPMCAS), on the melt crystallization kinetics of ITZ Forms I and II have been investigated. Form II structure is characterized by a unit cell similar to that of Form I, but with a different orientation of the dichlorophenyl groups. Form II displays a considerably higher crystal growth rate than Form I, which cannot be explicated by their difference in crystal density alone. Both polymers at 20% (w/w) significantly retard the crystallization of Forms I and II without altering the crystal structure of either polymorph. Crystallization kinetic analysis by the two-dimensional surface nucleation model suggests that the polymers inhibit the crystallization of ITZ from amorphous dispersions by reducing the molecular mobility in the molten state as well as augmentin...