  We developed a rapid polymorphic screening approach based on contracting
sessile microdroplets which offers several advantages: (1) achieves very high
supersaturation to facilitate formation of metastable forms (2) allows
systematic labeling of samples (3) gives access to statistical distribution of
polymorphic selectivity as a function of experimental conditions (4) ensures
the formation of crystal for each droplet, addressing the problem of
uncrystallized droplets in traditional microfluidics. We studied the
competitive nucleation of D-mannitol polymorphs and investigated the effect of
droplet volume on polymorphic selectivity. We showed that our observed
polymorph distributions at different volumes are qualitatively consistent with
the predictions of classical nucleation theory except for very small volumes
where thermodynamic confinement or surface effects could play a substantial
role. Overall, our microfluidic approach can be a promising tool not only for
routine screening of pharmaceutical polymorphs in the industrial context but
also in the fundamental understanding of the mechanisms underlying the
competitive nucleation of polymorphs.
