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.