Crystal Imperfections in Molecular Crystals: Physical and Chemical Consequences

Nanometer-Scale Residual Crystals in a Hot Melt Extruded Amorphous Solid Dispersion: Characterization by Transmission Electron Microscopy

“…As the starting material of drug crystals is likely to contain imperfections and local disorder at the surface and in the bulk of the crystal, , these defects are the likely sites for initiation of phase transformation due to thermal or mechanical stresses because of higher overall free energy resulting from the presence of mixed amorphous and crystalline phases. Chemical and thermal etching studies have demonstrated that dissolution is initiated at defect sites , and that dissolution rate correlates to defect density .…”

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

“…Surface imperfections and growth defects were observed in some crystalline starting materials (Figure 2, Figure 3), which is not unexpected, as such imperfections are common on the surface and in the bulk of organic crystals. 42,43 These growth imperfections served as sites for initiation of dissolution due to their higher surface energy, and dissolution would be accelerated at these sites. By polarized light microscopy (Figure 5), these growth imperfections served as sites for fragmentation early in the dissolution process.…”

“…Imperfections and local disorder at crystal surfaces and in the bulk are common in organic crystals, originating during crystallization or other downstream processing operations. − Such defects, in the form of vacancies, impurities, dislocations, and grain boundaries, are sites of higher energy and greater molecular mobility, and may contribute to the initiation of physical or chemical transformations, such as melting, solubilization, polymorphic transitions, or mechanical failure . Crystal defects have been linked to increased dissolution rates. − Local stress fields in solids result from virtually all types of reactions and therefore have important chemical and physical consequences. − Defects have also been shown to impart localized stress, helping to explain their role in enhancing dissolution rates and facilitating physical or chemical transformations .…”