A new polymorph of succinic acid is an unusually challenging test for metastable polymorph prediction.

Trifluoroacetate salt contamination of peptides represents a challenging issue related to solid phase peptide 8 synthesis and purification because it affects the chemical and biological properties of peptides. Purification of such materials is 9 typically performed through a two-step post-synthetic procedure based on chromatography followed by ion exchange. For the 10 first time, co-crystallization is presented in this study as a possible alternative and advantageous single-step method for the 11 obtaining of TFA-free crystals of a dipeptide. A trifluoroacetate-contaminated L-Leu-L-Leu dipeptide has been used for co-12 crystallization experiments along with different solid coformers. New multicomponent crystals containing only the title 13 compound and the second co-crystal formers are described in this work. Such results represent a novelty in the field of peptide 14 chemistry and a valid proof for the use of crystal engineering-based method for a combined purification and crystallization 15 strategy.

Dextrans are a class of carbohydrate polymers extensively applied in pharmaceutical applications, particularly as drug conjugate macromolecular carriers or drug delivery systems. These polysaccharides enable the stability of the therapeutics to be improved and for them to be delivered in a controlled manner, via either the parenteral and oral routes. In the latter case, due to their gel forming ability they may have potential as hydrophilic matrix tablets for sustained drug release.In this paper, we investigated the behaviour of different molecular weight (1, 40, 500 and 2300 kDa) dextrans as tabletting excipients. Powder particle size and hygroscopic studies have been reported, together with tabletability, tablet stability and tablet swelling. Moreover we use tramadol as model compound to evaluate the ability of dextrans to control drug dissolution. The results suggest that dextrans with lower molecular weights may be a promising excipient to be used as filler for immediate release tablets, due to their good tabletability and fast dissolution rate, while dextrans with higher molecular weights could be an efficient disintegrant due to their swelling ability.3

In a previous contribution, entitled “First Steps for the Direct Purification of l-Leu-l-Leu Dipeptide through Cocrystallization”, we reported and evidenced cocrystallization as a route to purify freshly synthesized trifluoroacetic acid (TFA)-contaminated Leu-Leu peptides. In this contribution ternary and quaternary crystal forms, isolated as transient phases to the previously reported pure cocrystals, are presented. This contribution and the one previously reported present the outcomes of large cocrystallization screening undertaken on the l-Leu-l-Leu dipeptide, where a competing range of multiple crystal forms from target cocrystal to TFA salt is accessible. As a key point for this contribution we report the isolation of transient phases that consist of Leu-Leu peptide (both with amidic and carboxylic C-terminals) either with pyridazine, 1H-pyrazole, pyridine N-oxide, or pyrazine plus TFA, or solvent alcohol or water with TFA. Such a diversity of multicomponent phases add further to the understanding of the differential crystallization process established when cocrystallization is used to purify the crude synthesized peptide product contaminated with TFA. A description of the overall packing landscape was undertaken from a crystal engineering point of view to illustrate how the presence of trifluoroacetate anions, strong hydrogen bond acceptors, affect the crystal packing. Typically, the Leu-Leu peptide forms a multilayered structure with guest in cavities between the layers; however, alternative novel arrangements were also seen. The structures are part of a wide landscape of possible complexes that are difficult to isolate, as they often represent transient phases that are hard to reproduce. Nevertheless, the reported phases give further insight into the purification through cocrystallization pathway and, critically, help to understand the interplay between crystal growth and the packing landscape.

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