Prenucleation Self‐Assembly and Chiral Discrimination Mechanisms during Solution Crystallisation of Racemic Diprophylline

Abstract

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Limitations of Preferential Enrichment: A Case Study on Tryptophan Ethyl Ester Hydrochloride

“…The following protocol, based on the work of Brandel et al and Gervais et al , was applied to check if the DLWE crystal structure allows for an enantiomeric permutation. A supercell of 3 × 3 × 3 cells containing 54 tryptophan ethyl ester hydrochloride salts was constructed.…”

Crystallization from the Amorphous State of a Pharmaceutical Compound: Impact of Chirality and Chemical Purity

“…In Figure 7, one can compare the diffraction patterns of form RII obtained by solvent crystallization (for comparison purpose) or produced by heating the SCM up to 125 °C with that collected after annealing of the amorphous sample at 80 °C. It appears that Additionally, Figure 8 compares selected ranges of Raman shifts (lattice vibrations at low wavenumbers and carbonyl or CC double bond stg vibrations) 59,60 for the same PC particle obtained at 90 °C and subsequently heated up to 125 °C with reference to spectra recorded for RII and for amorphous DPL. It is evidenced from these data that the Raman signature of PC resembles that of the material and that heating up to 125 °C induces a transition from PC to RII.…”

Enabling Direct Preferential Crystallization in a Stable Racemic Compound System

“…Beside the careful analysis of chiral discrimination mechanism 16 it can be presumed that the key parameter for the successful implementation of PC despite the absence of a stable conglomerate is the use of a solvent in which spontaneous nucleation is strongly delayed, giving rise to a large MSZW, even at high supersaturation. This feature allows the use of metastable equilibria associated to the conglomerate whereas the stable equilibria of the racemic compound can be overpassed.…”