Effect of Particle Size and Morphology on the Dehydration Mechanism of a Non-Stoichiometric Hydrate

Chapter 2. Solid‐State NMR in Drug Discovery and Development

“…For example, in Figure 2.13, a crystalline phase of a drug molecule known as Form K is shown. 188 Small peaks, denoted by arrows, show a suspected phase impurity. Comparison of the spectrum with 13 C CP-TOSS spectra obtained after microwave heating of the sample shows the growth of the phase impurity, and allows for the conclusion that the sample of Form K contains Form A, which can be converted to phase-pure Form A after heating.…”

“…190 An example is shown in Figure 2.15 for the previously discussed small molecule API, which contains a trifluoromethyl group, allowing for comparison of the 19 F-13 C CP-MAS spectra of several polymorphs and a hydrate. 188 The hydrate was previously subjected to a detailed structural analysis by SSNMR, SCXRD and other techniques. 188 The spectra in 19 F-13 C CP-MAS (n r ¼ 8 kHz) of different crystalline forms of this API obtained with a 5 ms contact time.…”

“…188 The hydrate was previously subjected to a detailed structural analysis by SSNMR, SCXRD and other techniques. 188 The spectra in 19 F-13 C CP-MAS (n r ¼ 8 kHz) of different crystalline forms of this API obtained with a 5 ms contact time. Differences in intermolecular packing are highlighted by this experiment, which shows short-range interactions between fluorine and carbon sites.…”

“…2 H and 17 O). 18,188,197,198 Hydrates and solvates represent two well-known classes of multicomponent crystals or inclusion complexes. Cocrystals represent a larger class of multicomponent crystal material made up of two or more components, typically in a stoichiometric ratio, where each separate component exists as a solid at room temperature.…”

Imaging Dehydration Kinetics of a Channel Hydrate Form of the HIV-1 Attachment Inhibitor Prodrug BMS-663068

“…This is an area that has not been widely described but has shown the potential to have a disproportionate effect on material‐handling properties in drug‐product processing and performance parameters such as compaction, flow, granulation behavior, segregation, and powder dispersion . Solid‐state nuclear magnetic resonance (ssNMR) characterization was carried out to give qualitative and quantitative information on solid‐state interactions . In particular, this would encompass whether the uptake of water was reversible and whether repeated cycling from low to high humidity affected the conformation and the crystal lattice.…”