Dissolution of Indomethacin Crystals into a Polymer Melt: Role of Diffusion and Fragmentation

The dissolution or melting of a crystalline drug into a molten polymeric matrix underpins the fabrication of a number of drug delivery systems. However, little is known about how crystals dissolve in such viscous matrices. Herein, the heat-induced dissolution of indomethacin crystals into a molten polymer, copovidone, was evaluated, probing changes in crystal features at multiple length scales using various microscopy techniques. Diffusion of the drug into the polymer film was observed by elemental composition analysis (scanning electron microscopy with energy-dispersive X-ray analysis). Under polarized light microscopy, irregular dissolution patterns were observed, in which channels and holes were seen forming in the crystals, which then resulted in fragmentation. At shorter length scales by scanning and transmission electron microscopy, crystals demonstrated a range of channel formation and fragmentation behaviors. Defect sites intrinsic to the bulk crystals were hypothesized to be the origin of the dis...