Fast Surface Crystallization of Molecular Glasses: Creation of Depletion Zones by Surface Diffusion and Crystallization Flux

Abstract

Molecular glasses can grow crystals much faster at the free surface than in the interior. A property of this process is the creation of depressed grooves or depletion zones around the crystals on the initially flat amorphous surface. With scanning electron microscopy and atomic force microscopy, we studied this phenomenon in indomethacin, which crystallizes in two polymorphs (α and γ) of different morphologies. The observed depletion zones are well reproduced by the known coefficients of surface diffusion and the velocities of crystal growth. At the slow-growing flanks of needle-like α IMC crystals, depletion zones widen and deepen over time according to the expected kinetics for surface diffusion responding to a crystallization flux. Before fast-advancing growth fronts, depletion zones have less time to develop; their steady-state dimensions agree with the same model revised for a moving phase boundary. These results support the view that surface diffusion enables fast surface crystal growth on molecular glasses. Our finding helps understand crystal growth in thin films in which the formation of deep depletion zones can cause dewetting and alter growth kinetics.

Amorphous Drug-Polymer Salts

“…This supports the notion that surface crystal growth is controlled by surface diffusion [ 34 , 35 ]. This conclusion is further supported by the fact that surface crystals grow upward and laterally without deep penetration into the bulk and are surrounded by grooves created by the surface motion of molecules toward the crystal [ 36 , 37 ].…”

Bubble-induced fast crystal growth of indomethacin polymorphs in a supercooled liquid

“…The surface crystal growth rate was measured by tracking the crystals spontaneously nucleated at the free surface. Previous studies have reported that -IMC exhibits a much faster crystal growth at the free surface than in the interior (Hasebe et al, 2014(Hasebe et al, , 2015Musumeci et al, 2016). In this work, we carefully measured the growth kinetics in the supercooled liquid state, either at the free surface or in the bulk, by tracking the speed at which the growth front advanced.…”

“…For this rapid surface crystal growth, the crystal could grow edgewise and extend tens to hundreds of nanometres above the amorphous film (Sun et al, 2011). Another intriguing property of surface crystal growth is the formation of depletion zones in the amorphous matrix near the crystal growth frontier (Hasebe et al, 2014(Hasebe et al, , 2015. Recent studies have revealed that fast surface crystal growth is related to the extremely fast molecular diffusion at the free surface (Yu, 2016;Zhu et al, 2011;Huang et al, 2017;Brian & Yu, 2013;Zhang et al, 2015;Chai et al, 2014).…”

“…Interestingly,and -IMC have vastly different growth morphologies, with the former growing as compact domains and the latter as needle shapes (Hasebe et al, 2014). As a result, these IMC polymorphs respond differently to the onset of liquid flow when the glass is heated to a supercooled liquid (Hasebe et al, 2014(Hasebe et al, , 2015Musumeci et al, 2016. In this study, we focus on the crystal growth behavior of IMC polymorphs ( and forms) when the crystals encounter bubbles in the interior of the supercooled liquid. We find that the crystal growth of both the and form could be substantially accelerated by bubbles and exhibits polymorph-dependent behavior at the free surface on increasing the temperature to above T g .…”

New directions in pharmaceutical amorphous materials and amorphous solid dispersions, a tribute to Professor George Zografi – Proceedings of the June 2016 Land O’Lakes Conference

“…Experiments have shown that glasses exhibiting van der Waals forces (vdW glasses) exhibit faster surface diffusion than glasses with significant hydrogen bonding (network glasses). Surface mobility was found to have a central role in the stability of molecular glasses, with surface crystal growth occurring laterally and upward, not down into the bulk (Hasebe et al 2015). Glasses with faster surface diffusion result in faster crystal growth, and result in depletion zones on the surface (Fig.…”