Control of Heterogeneous Nucleation via Rationally
Designed Biocompatible Polymer Surfaces with Nanoscale Features
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Abstract
Direct control of nucleation in a
crystallization process is difficult
to achieve but offers many potential benefits to the food, chemicals,
and pharmaceutical industries. We demonstrate a rational approach
for designing and fabricating biocompatible polymer films that can
drastically enhance nucleation rates and enable polymorph selection
of small-molecule compounds. The core design philosophy was to calculate
angles between major crystal faces and determine suitable substrate
geometry to use for enhancing heterogeneous nucleation. Aspirin and
indomethacin were used as model compounds; poly(vinyl alcohol) (PVA)
with no additional chemical modification was made into films and imprinted
with nanoscale features. Nucleation induction time experiments showed
that using PVA films significantly reduced the nucleation induction
time at a fixed supersaturation due to favorable chemical interactions
and could be further reduced when the angles of the nano-indentations
on the substrate matched the angles between different crystalline
faces. X-ray diffraction (XRD) was used to reveal the interactions
between the model compounds and PVA to suggest possible molecular
packing in the indentations. Induction time and XRD results demonstrated
validity of the rational design approach based on angle-directed nucleation.
Finally, polymorph selection toward γ-indomethacin with PVA
substrates showed that it is possible to control polymorph composition
of the final crystalline product by kinetically controlling the nucleation
process. For the aspirin system, the 85° angle led to the highest
rate of nucleation; for the polymorphic indomethacin system, XRPD
results showed that the gamma form preferentially formed on the PVA
films with 65° and 80° angles leading to the largest reduction
in nucleation induction time