Crystallization of Organic Glasses: Effects of Polymer Additives on Bulk and Surface Crystal Growth in Amorphous Nifedipine

ABSTRACTPurposeTo study the influence of polymer additives on bulk and surface crystal growth in organic glasses (amorphous solids), which are being investigated for delivering poorly soluble drugs and in this role must resist crystallization. Recent studies have discovered new modes of crystal growth that emerge as organic liquids are cooled to form glasses: one existing in the bulk (GC growth) and another at the surface, both leading to crystal growth much faster than predicted by standard theories.MethodsBulk and surface crystal growth rates were measured in nifedipine glasses doped with polyvinylpyrrolidone (PVP) of different molecular weights. AFM enabled observation of the microstructure of surface-growing crystals.ResultsPolymer additives influence bulk and surface crystal growth differently. For every weight percent of PVP added, surface crystal growth of nifedipine slows by two times at 12°C below Tg, whereas bulk crystal growth slows by 10 times. In contrast to the polymers, the VP dimer had little effect on crystal growth.ConclusionsPolymer additives inhibit crystal growth in nifedipine glasses more strongly in the bulk than at the surface. The effectiveness of crystallization inhibitors depends not only on intermolecular interactions but also on molecular sizes.

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