Investigation of thermal decomposition as a critical factor inhibiting cold crystallization in amorphous sucrose prepared by melt-quenching

Controlling desolvation through polymer-assisted grinding

“…In particular, a long-wavelength oscillation in the difference curve may indicate modifications to the intermolecular packing, similar to that observed in amorphous drug-polymer dispersions 37,41 and saccharide mixtures. 42,43 As a further example, in Figure 4(c), we show a similar comparison in which 2(thp)•3(2-pyr) is fit by the pure constituent phase thp Modifications to small molecule crystallite size and size distribution on co-grinding with polymers is a well-established phenomenon and therefore not surprising in this case. 44 Differences between the POLAG samples and pure components of the thp-polymer mixtures observed by Raman and PDF (SI Sections 4.5 and 4.6) suggest that the crystallite size reduction is accompanied by structural modifications to thp.…”

Local Structural Effects Due to Micronization and Amorphization on an HIV Treatment Active Pharmaceutical Ingredient

“…If we assume this is all residual solvent, the calculated mole ratio would be 0. weight percent of impurities has been observed, for instance through degradation impurities in melt quenched sucrose. 8 It is thus especially important to consider the effects of residual impurities on the structural packing in amorphous formulations, even at small weight percentages, in regard to differences in the PDF or in the shapes of as-measured amorphous diffractograms, which could otherwise be interpreted as a polyamorphic effect. 58,59 SSNMR of Crystalline, Micronized, and Amorphous I.…”

“…Taken together, these suggest that DCM is present in the microfluidic formulation, and the possibility that it either indirectly induces conformational modifications in I involving H-bonds or directly interacts with I . The modification of both structural packing and physicochemical properties induced by small weight percent of impurities has been observed, for instance through degradation impurities in melt quenched sucrose . It is thus especially important to consider the effects of residual impurities on the structural packing in amorphous formulations, even at small weight percentages, in regard to differences in the PDF or in the shapes of as-measured amorphous diffractograms, which could otherwise be interpreted as a polyamorphic effect. , …”

“…different morphologies, domain sizes, modifications of domain structure, interactions between different crystalline and/or amorphous phases, or leftover impurities from the processing medium or degradation. 8 The difficulty is, however, to determine what the atomic-scale structural differences are. 9−11 This includes detection and quantification of amorphous phases or nanocrystalline content and changes in the conformation state or local packing of molecules in those phases, i.e.…”

“…Different micronization and amorphization processes can lead to substantial differences in physicochemical properties such as dissolution performance and product stability. − These properties can be greatly affected by the thermodynamic and kinetic landscapes accessed, for instance through thermal, versus mechanical, or solution-based amorphization, resulting in e.g. different morphologies, domain sizes, modifications of domain structure, interactions between different crystalline and/or amorphous phases, or leftover impurities from the processing medium or degradation . The difficulty is, however, to determine what the atomic-scale structural differences are. − This includes detection and quantification of amorphous phases or nanocrystalline content and changes in the conformation state or local packing of molecules in those phases, i.e.…”