Themed collection Pharmaceutical Solids

Engineering and manufacturing of pharmaceutical cocrystals.

From Saridon to Entresto: the journey of pharmaceuticals from the first drug–drug combination of propyphenazone and pyrithyldione in 1937 (left) to the most recent monosodium sacubitril and disodium valsartan in 2015 (right).

Development of mechanochemistry for API synthesis and pharmaceutical solid form screening signals the emergence of medicinal mechanochemistry – a discipline at the interface of medicinal chemistry and sustainable synthesis.

Case studies illustrate how crystal structure prediction calculations can complement industrial solid form screening.

A unique approach is applied in preparing the first ‘air-stable’ formulation of form III of paracetamol, long regarded as a highly unstable form.

A new method of inducing the crystallisation of metastable polymorphs by isomorphous templating has been developed using DHC-II crystal surfaces to reproduce CBZ-V and to produce a new polymorph, CYH-III.

A transferable, simple, route to previously elusive and novel polymorphic forms of important active pharmaceutical ingredients is demonstrated using N-heterocyclic co-molecules to influence the self-assembly crystallisation process in a multi-component environment.

A designed multi-component templating approach to paracetamol form-II provides a reproducible route to scalable (>100 g in a single run) production of this previously elusive polymorph, with its enhanced compressibility and solubility.

The potential of NMR crystallography to verify molecular crystal structures deposited in structural databases is evaluated, with two structures of the pharmaceutical furosemide serving as examples.

The highly polymorphic compound ROY was the subject of a co-crystal screen. No co-crystals were found, but the study highlights the potential for future prediction of co-amorphous behaviours by determining an interaction between ROY and pyrogallol.

This work reports how and why solution pH alters cocrystal solubility and stability relative to drug.

The unusual phenomenon of the formation of the kinetic form as against the thermodynamic form upon slow cooling of boiling aqueous solution in the case of diuretic drug acetazolamide is rationalized in terms of “hybridization induced polymorphism” based on extensive experimental and theoretical investigations.

A novel hemihydrate form of the antileukemia drug 6-mercaptopurine is discovered. This hemihydrate shows double the solubility and almost three times the bioavailability of the commercially used monohydrate form.

An amorphous acetaminophen nanolayer is shown to determine the surface energy of acetaminophen nanocrystals grown in controlled porous glasses.

This report highlights the discovery of new polymorph ‘form XV’, and the crystal structure of the elusive form V of the anticonvulsant drug phenobarbital.

The pharmaceutical cocrystal alloy of NTZ-PABA : NTZ-PASA (0.75 : 0.25) exhibits a higher pharmacokinetic profile than the individual cocrystals and nitazoxanide.

Color polymorphs of aldose reductase inhibitor epalrestat also exhibit configurational, conformational and synthon differences. Form I is the stable modification under temperature and humidity conditions.