Producing lattice defects by drying processes

Evaluation of the Use of Ea (Activation Energy) as a Quantitative Indicator of Physical Stability of Indomethacin Solvates: Methanolate and Tertiary Butyl Alcohol Solvate

“…Depending on the form desired (desolvated solvate, amorphous form, or crystalline), drying can have desirable or undesirable consequences, and loss of solvent or desolvation may lead to possible changes in the solubility, bioavailability, and/or stability of the drug molecule. [2][3][4][5] Desolvation via drying can be difficult to control especially during scale-up having as a consequence issues with batch-tobatch reproducibility. Furthermore, drying is difficult to control during scale-up and can often lead to the formation of an undesirable crystal form or mixtures of forms.…”

“…Drying can result in full or partial loss of solvent (including water). Depending on the form desired (desolvated solvate, amorphous form, or crystalline), drying can have desirable or undesirable consequences, and loss of solvent or desolvation may lead to possible changes in the solubility, bioavailability, and/or stability of the drug molecule. − …”

Surface Characterization: Understanding Sources of Variability in the Production and Use of Pharmaceuticals

“…It has long been recognized that processing can induce disorder in apparently crystalline materials. The influences of drying (Huttenrauch & Keiner 1979), spray drying (Mumenthaler & Leuenberger 1991), lyophilization (Pikal et a1 1978), mixing (Konno 1990) and tablet compaction (Ahlneck & Alderborn 1989) have all been documented, and it is probable that every other unit process in production can affect the degree of crystallinity of certain materials. The presence of amorphous regions in crystalline solids can be beneficial in terms of enhanced dissolution rate and increased bioavailability, and possibly due to altered interaction with other formulation components.…”

Effects of mechanical processing on phase composition

“…That mechanical processing can produce defects in crystalline solids has been known for some time,28 and it is equally established that defects can influence powder properties 29. Point defects can be classified30 as vacancies (lattice sites from which units are missing), interstitials (molecules that have slipped into voids between lattice sites), or substitutionals (a foreign molecule occupying a lattice site).…”