Themed collection Editor’s Collection: Polymorphism in Molecular Crystals

We review the polymorphism of p-aminobenzoic acid (pABA), a model drug compound whose crystallisation and polymorphic behaviour has been extensively studied in recent years.

Two polymorphs of a diketopyrrolopyrrole dye, one yellow and the other orange, were obtained.

Surface metal organic framework substrates were engineered as heterogeneous surfaces and the importance of these designed surfaces towards polymorphs and morphological engineering was discussed for the first time.

When crystals of four polymorphs – a stable α-form and three metastable ones (β-, γ-, δ-forms) – are simultaneously present in a pressure cell, immersed in a 1 : 1 pentane–isopentane mixture, the least stable β-form recrystallises exclusively into the γ-form (if no δ-form seed is present) or concomitantly into the γ- and δ-forms (if a seed of the δ-form is present).

Twelfth polymorph of the anti-psychotic drug aripiprazole was discovered where its active metabolite acted as a template during recrystallization.

The development of rational crystallisation strategies in polymorphic systems requires the experimental manipulation of both kinetics and thermodynamics.

The amino acid L-threonine undergoes three phase transitions between ambient pressure and 22.3 GPa which modify both hydrogen bonding and the molecular conformation.

Crystallising D-mannitol in printed droplets provides new insights into understanding the effect of foreign surfaces on the formation of its polymorphs.

Ball mill neat grinding leads to smoother whereas liquid assisted grinding leads to rougher pharmaceutical forms.

We show that seeding is not always sufficient to control cystal polymorphism and illustrate how kinetic modeling can help controlling polymorphism.

The complex between sulfamethazine and saccharine (SMT–SAC) can exist in two polymorphs, one is a cocrystal and the other is a salt.

A polymorph of the widely employed coformer isonicotinamide crystallizing in the space group Pca2₁ is described for the first time.

Molecular crystal engineering seeks to tune the material properties by controlling the crystal packing.

This work studies a multitude of cocrystals obtained by combining chiral and/or racemic naproxen and proline, 17 in total.

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

Different types of mechanical treatment (tableting, grinding, milling, etc.) are important technological operations in the pharmaceutical industry.

A new polymorph and twisted semi-spherulites of L-malic acid are described and discussed in this work.

We report the crystal structures of four new squaric acid derivatives, i.e. three polymorphs of 3,4-bis((2-(dimethylamino)ethyl)amino)cyclobut-3-ene-1,2-dione (1a–c) and a cocrystal with resorcinol. A DFT study has been also carried out to investigate the supramolecular assemblies.

Pressure-resistant transformation between two polymorphs of tolazamide was monitored by X-ray diffraction and rationalized by DFT calculations.

Glibenclamide sodium salt polymorphs namely forms I and II showed differences in geometry of the central metal atom and ligand orientation. The solubility and stability of glibenclamide of GBA-K form I are superior for pharmaceutical development.

Crystal structure prediction studies of 4-aminoquinaldine monohydrate led, 80 years after its first synthesis, to the thermodynamically most stable form under conditions relevant for production and storage.

65 years ago McCrone postulated vanillin to be trimorphic but only one polymorph has been structurally characterized since. Herein, a new and rare crystal structure is reported. Selective crystallization of this polymorph was achieved using polymer induced heterogeneous nucleation.

Lattice energy, entropy and free energy differences for over 500 pairs of known polymorphs are computed and discussed.

A detailed morphological study on an organic polymorphic system highlighting the influence of desolvation on crystal habit.