The solid state of pharmaceuticals
Welcome to this CrystEngComm themed issue entitled “The solid state of pharmaceuticals.”
Polymorphism in p-aminobenzoic acid
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.
Determining short-lived solid forms during phase transformations using molecular dynamics
We demonstrate that elusive high-energy metastable crystal structures can be determined from molecular dynamics simulations.
Capturing a new hydrate polymorph of amodiaquine dihydrochloride dihydrate via heterogeneous crystallisation
A new polymorph of amodiaquine dihydrochloride dihydrate was obtained via heterogenous crystallization. This new polymorph showed difference in two-dimensional sheet structure compare to previously known polymorph.
Role of hydrogen bonding in cocrystals and coamorphous solids: indapamide as a case study
Crystalline and amorphous stable binary compounds of indapamide for high solubility and permeability.
Remarkable decrease in stiffness of aspirin crystals upon reducing crystal size to nanoscale dimensions via sonochemistry
Nano-dimensional crystals of aspirin generated through sonochemistry exhibit Young's modulus values an order of magnitude softer than macro-dimensional crystals.
Mechanochemistry vs. solution growth: striking differences in bench stability of a cimetidine salt based on a synthetic method
A mechanochemically prepared solvated salt of an archetypal blockbuster drug exhibits significantly different bench stability to analogous material made in solution.
Profoundly improved photostability of dimetronidazole by cocrystallization
Cocrystallization with saccharine (SAC) significantly improved photostability of dimetronidazole (DMZ), an veterinary antibiotic.
Pharmaceutical paroxetine-based organic salts of carboxylic acids with optimized properties: the identification and characterization of potential novel API solid forms
Reacting paroxetine HCl with oxalic, maleic, fumaric and L-tartaric acids results in the formation of novel molecular salts.
Paper
Conundrum of γ glycine nucleation revisited: to stir or not to stir?
Stirring promotes formation of the metastable α glycine polymorph, whereas stable γ glycine forms under quiescent conditions.
Tautomer selection through solvate formation: the case of 5-hydroxynicotinic acid
Different 5-hydroxynicotinic acid tautomers were selectively captured through solvate formation. The selectivity is lost once the memory of solvation is erased by removing the solvent from the crystal lattice.
Paper
Crystallisation in printed droplets: understanding crystallisation of D-mannitol polymorphs
Crystallising D-mannitol in printed droplets provides new insights into understanding the effect of foreign surfaces on the formation of its polymorphs.
On the prevalence of smooth polymorphs at the nanoscale: implications for pharmaceuticals
Ball mill neat grinding leads to smoother whereas liquid assisted grinding leads to rougher pharmaceutical forms.
Discovery and recovery of delta p-aminobenzoic acid
A new high-pressure recoverable form has been observed in the model system, p-aminobenzoic acid.
Paper
Ball size or ball mass – what matters in organic mechanochemical synthesis?
The effects of milling ball mass, size and material are isolated for a model mechanochemical co-crystallisation.
Solvent driven phase transitions of acyclovir – the role of water and solvent polarity
The pathways of transformations of acyclovir forms I and V induced by organic solvents and water have been identified. Significant differences in the thermal dehydration process of forms V and VI were observed.
The use of biocompatible crystalline substrates for the heterogeneous nucleation and polymorphic selection of indomethacin
A heteroepitaxial nucleation approach was used to control the phase selective nucleation of indomethacin using biocompatible, organic crystalline substrates.
Solvent-polymer guest exchange in a carbamazepine inclusion complex: structure, kinetics and implication for guest selection
Solvent–polymer guest exchange in a carbamazepine inclusion complex in a stirred solution was studied and a mechanism was proposed.
Paper
The solid state forms of the sex hormone 17-β-estradiol
The crystal structure of the female sex hormone has been established despite its high affinity for water.
Stanozolol–aromatic carboxylic acid crystalline complexes: flexible tautomeric/ionization states and supramolecular synthons
The various supramolecular synthons are constantly spinning in the crystal world.
Accuracy and reproducibility in crystal structure prediction: the curious case of ROY
Because of excessive electron delocalization, the polymorphs of ROY constitute a surprisingly challenging system for crystal structure prediction.
High thermal stability, pH responsive organogels of 2H-benzo[d]1,2,3-triazole derivatives as pharmaceutical crystallization media
2H-Benzo[d]1,2,3-triazole derivatives give rise to a supergelator that results in the crystallization of kinetic form I sulfathiazole.
Explaining crystallization preferences of two polyphenolic diastereoisomers by crystal structure prediction
Crystal structure prediction is used to understand the differences in crystallization of catechin and epicatechin, and to explore the predictability of solvate formation.
Design of 4-aminobenzoic acid two-component molecular crystals: prediction and experiments
Cocrystal formation of 4-aminobenzoic acid with a variety of pyrimidine, pyridine and benzamide derivatives has been investigated.
Co-crystallization and polymorphic behaviour of 5-fluorouracil
Hydrogen donors and acceptors in 5-fluorouracil allow the formation of co-crystalline compounds with nontoxic co-formers of the GRAS list and an alternative target-oriented synthon approach from methanol or ethanol to form II of 5-fluorouracil is presented.
Paper
Polymorph control in batch seeded crystallizers. A case study with paracetamol
We show that seeding is not always sufficient to control cystal polymorphism and illustrate how kinetic modeling can help controlling polymorphism.
Robust bulk preparation and characterization of sulfamethazine and saccharine salt and cocrystal polymorphs
The complex between sulfamethazine and saccharine (SMT–SAC) can exist in two polymorphs, one is a cocrystal and the other is a salt.
On the kinetics of solvate formation through mechanochemistry
We demonstrate that solvates obtained through mechanochemistry are the thermodynamic products, and that the kinetics of solvate formation are related to the easiness of breaking the reactant crystals.
About this collection
This themed collection focuses on the experimental and computational investigation of crystal polymorphism, solvate and hydrate formation of pharmaceutical compounds. Topics range from the study of nucleation and crystallisation to the discovery, computational prediction and design of new solid forms of drug compounds.