Experimental
and computational morphology of three polymorphs of the free base of
Venlafaxine: A comparison of morphology prediction methods
M.A. Deij, J. van Eupen, b, H.
Meekes, P. Verwer, P. Bennema and E.
Vlieg
Abstract:
In this paper the experimental and
the computational studies of the
morphology of three polymorphs of the free base of Venlafaxine
((N,N-dimethyl)-2-(1-hydroxy cyclohex-1-yl)-2-(4-methoxyphenyl)
ethylamine) are reported. The morphology of all polymorphs has been
predicted using the Bravais–Friedel–Donnay–Harker method, the
attachment energy method and kinetic Monte Carlo growth simulations and
these predictions have been compared with experimental observations.
The Monte Carlo simulations allow for a detailed simulation of the
growth process, including driving force and growth mechanism, which
leads to a semi-quantitative prediction of the growth morphologies of
all three phases.
For phase I two distinct growth
habits are found experimentally under
the same conditions. This is explained by the occurrence of a spiral
growth mechanism in one of the two, which was observed using AFM and
which is also supported by the Monte Carlo simulations. The habit of
phase II could only be explained from simulations when a spiral growth
mechanism is assumed; the shape of phase III could not be modeled
accurately from the Monte Carlo simulations. Although the shape of the
crystal is reproduced accurately, some of the indices of the faces
predicted are not in agreement with the indices measured. The
deviations are interpreted to be due to the presence of domains in the
crystals as a result of the layered structure.