Co-crystal screening is routinely undertaken using high-throughput solution growth. We report a low- to medium-throughput approach, encompassing both melt and crystallization step as route the identification of co-crystals. Prior studies, growth was included utilizing Kofler mixed fusion method. This method allowed elucidation thermodynamic landscape within binary phase diagram found increase overall efficiency. The pharmaceutically acceptable adduct nicotinamide selected screened against...

A combined modeling and experimental strategy has been applied to the problem of stabilisation a metastable conformational polymorph. For first time additives have successfully selected which by virtue their conformation are able selectively inhibit appearance stable β polymorph l-glutamic acid hence stabilize α structure.

This contribution reviews the area of polymorph selection during solution crystallization using known and predicted structures. In particular, an overview what has been learned about relationship between structure kinetics interplay thermodynamics is presented. review adds to debate by discussing future challenges that we envisage in realizing as a crystal engineering exercise highlighting role packing landscape approach may contribute manipulating polymorph.

In the world of crystal engineering in which focus effort is on assembly molecular species by crystallisation, surprisingly little attention has been paid to actual nucleation and crystallisation processes involved. This Highlight explores structural aspects process a range small molecule systems. It uses combination thermodynamic, modelling approaches order progress our understanding link between liquid phase assemblies, constitute growth units, their solid state counterparts,...

In this feature article we will focus on the issues relating to crystal growth of co-crystals, with a particular emphasis drug development. The initial perspective is relevant literature examples that may be able inform our understanding regards co-crystal crystallisation and allied supramolecular concepts. second part contains selected from own work, which add perspective. Topics include; nucleation templates, in situ synchrotron XRD studies, solid-state synthesis through mixing screening...

Sulfathiazole, a compound that forms four known crystal structures, has been examined with view to understanding its polymorphism. A graph set approach was used classify the structural differences and similarities of polymorphs, results which indicated packing motifs common three structures. By combining this analysis experimental morphological data, it possible examine origins observed solvent dependence polymorph appearance in system. In particular, link between hydrogen-bond each form...

The relationship between molecular self-assembly processes and nucleation during crystallization from solution is an important issue, both in terms of fundamental physical chemistry for the control application crystal engineering materials chemistry. This contribution examines extent to which occurrence polymorphism can be used as indicator nature aggregation supersaturated solutions. For specific case 2,6-dihydroxybenzoic acid a combination solubility, spectroscopic, crystallization,...

Progression from drug to co-crystal medicine.

This contribution describes the kinetics of solution mediated phase transformation between forms 1 and 2 dihydroxybenzoic acid. It is shown how a combination kinetic, morphological, modeling data can be used to give full description rate-determining process in such transformation. Surprisingly, secondary nucleation found dominate kinetic processes. Such phenomenon well-known continuous crystallization but reported here for first time polymorphic observation has significant consequences...

The formation of crystalline molecular complexes benzoic acid and isonicotinamide with 1:1 2:1 compositions has been investigated through solution cocrystallization. complex was solely obtained from ethanol solutions, while either could be grown aqueous methanol by variation the initial composition. crystal structures a monohydrate were determined single X-ray diffraction. intermolecular interactions in structure compared other published carboxylic acid:isonicotinamide complexes, which...

Formulating pharmaceutical cocrystals as inhalable dosage forms represents a unique niche in effective management of respiratory infections. Favipiravir, broad-spectrum antiviral drug with potential pharmacological activity against SARS-CoV-2, exhibits low aqueous solubility. An ultra-high oral dose is essential, causing patient compliance. This study reports Quality-by-Design (QbD)-guided development carrier-free dry powder formulation containing 1:1 favipiravir–theophylline (FAV-THP)...

This paper describes the combined application of crystal structure prediction and targeted experimental crystallization to diflunisal, a fluorinated, aromatic carboxylic acid. Graph set analysis has been used analyze classify structural predictions, solvents have selected promote formation crystals containing most commonly predicted hydrogen-bonding motifs. Accordingly, four new structures this material were solved, two solvates polymorphs. example further highlights both insight offered by...

At long last, the crystal structure of metastable form benzamide, whose existence has been known for over 170 years, finally solved by using a combination in situ crystallization, high-speed synchrotron X-ray powder diffraction, and global-optimization methods determination (see picture).

Experimental solubilities of budesonide, hydrocortisone, and prednisolone in ethanol + water mixtures at 298.2 K are reported. The solubility drugs was increased with the addition reached maximum values volume fractions 90 %, 80 % ethanol. Jouyban−Acree model used to fit experimental data, were reproduced using previously trained versions data monosolvents which overall mean relative deviations (OMRDs) models 5.1 6.4 37.7 35.9 respectively, for fitted model, version mixtures, generally...

Previously reported methods for co-crystal synthesis have employed a variety of strategies and these include co-grinding, co-precipitation, growth from the solution, melt slurry (M. Zaworotko, Polymorphism in Co-crystals Pharmaceutical Co-crystals, XX Congress International Union Crystallography, Florence, 2005) spontaneous formation without pre-milling activation (C. Maheshwari, J. Jayasankar, N. A. Khan, G. E. Amidon Rodriguez-Hornedo, CrystEngComm, 2009, 11, 493–500). In this contribution...

Abstract Four new ternary crystalline molecular complexes have been synthesised from a common 3,5‐dinitrobenzoic acid (3,5‐dnda) and 4,4′‐bipyridine (bipy) pairing with series of amino‐substituted aromatic compounds (4‐aminobenzoic (4‐aba), 4‐( N , ‐dimethylamino)benzoic (4‐dmaba), 4‐aminosalicylic (4‐asa) sulfanilamide (saa)). The crystals were created through the application complementary charge transfer hydrogen‐bonding interactions. For these systems dimer was charge‐transfer interaction...

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

In this work, we revisit the question of metastable crystal form benzamide. This was first identified in 1832 by Liebig and Woehler, but its structure has never been determined. It is shown how a combination microscopic, spectroscopic, diffraction techniques have used to solve, finally, highly Form II The morphology, disorder, nucleation under labile conditions lead some speculation as origins such an unstable polymorph.

The multicomponent ternary complex of 4-dimethylaminobenzoic acid (4-DABA), 3,5-dinitrobenzoic (3,5-DNBA), and 4,4′-bipyridine (BIPY) has been studied by variable temperature X-ray neutron diffraction. Proton disorder is observed within the 4-DABA homodimers present quantitatively evaluated from data. effect crystal environment in particular pyramidalization nitrogen atom molecule consequential on presence hydrogen are discussed with reference to previously determined pure structure binary...