10.1021/acs.cgd.7b00375.s001 Shuai Zhang Shuai Zhang James F. Britten James F. Britten Albert H. L. Chow Albert H. L. Chow Thomas W. Y. Lee Thomas W. Y. Lee Impact of Crystal Structure and Polymer Excipients on the Melt Crystallization Kinetics of Itraconazole Polymorphs American Chemical Society 2017 HPMCAS single-crystal X-ray diffraction Form II hydroxypropylmethyl cellulose acetate succinate crystal growth rate polymer Form II displays Form II structure PVPVA Kollidone VA 64 ITZ surface nucleation model crystal structure Melt Crystallization Kinetics 2017-04-26 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Impact_of_Crystal_Structure_and_Polymer_Excipients_on_the_Melt_Crystallization_Kinetics_of_Itraconazole_Polymorphs/4956815 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 augmenting the crystal–melt interfacial free energy. Form II is more sensitive than Form I to the growth inhibition by either polymer, which can be attributed to a much larger increase in the crystal–melt interfacial free energy brought about by much stronger polymer adsorption on the crystal surface of Form II.