Engineering and manufacturing of pharmaceutical co-crystals: a review of solvent-free manufacturing technologies
Engineering and manufacturing of pharmaceutical cocrystals.
Pharmaceutical cocrystals: walking the talk
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).
Towards medicinal mechanochemistry: evolution of milling from pharmaceutical solid form screening to the synthesis of active pharmaceutical ingredients (APIs)
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.
Can computed crystal energy landscapes help understand pharmaceutical solids?
Case studies illustrate how crystal structure prediction calculations can complement industrial solid form screening.
Stabilisation of metastable polymorphs: the case of paracetamol form III
A unique approach is applied in preparing the first ‘air-stable’ formulation of form III of paracetamol, long regarded as a highly unstable form.
Isomorphous template induced crystallisation: a robust method for the targeted crystallisation of computationally predicted metastable polymorphs
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.
Selective preparation of elusive and alternative single component polymorphic solid forms through multi-component crystallisation routes
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.
Controlled production of the elusive metastable form II of acetaminophen (paracetamol): a fully scalable templating approach in a cooling 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.
Furosemide's one little hydrogen atom: NMR crystallography structure verification of powdered molecular organics
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.
Stabilisation of an amorphous form of ROY through a predicted co-former interaction
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.
How cocrystals of weakly basic drugs and acidic coformers might modulate solubility and stability
This work reports how and why solution pH alters cocrystal solubility and stability relative to drug.
Acetazolamide polymorphism: a case of hybridization induced polymorphism?
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.
Improved pharmacokinetics of mercaptopurine afforded by a thermally robust hemihydrate
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.
Pharmaceutical nanocrystals confined in porous host systems – interfacial effects and amorphous interphases
An amorphous acetaminophen nanolayer is shown to determine the surface energy of acetaminophen nanocrystals grown in controlled porous glasses.
Polymorphism in phenobarbital: discovery of a new polymorph and crystal structure of elusive form V
This report highlights the discovery of new polymorph ‘form XV’, and the crystal structure of the elusive form V of the anticonvulsant drug phenobarbital.
Cocrystals and alloys of nitazoxanide: enhanced pharmacokinetics
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: configurational, conformational and synthon differences
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.
About this collection
This web themed collection, guest edited by Ashwini Nangia, Jonathan W. Steed and Michael D. Ward, is a celebration of the state of the art and future perspectives in the field of “Pharmaceutical Solids”. It will highlight the role that fundamental chemistry plays in the understanding, characterisation and design of solid state organic materials of relevance to the pharmaceutical sector. Topics such as polymorphism, co-crystal formation, novel crystallisation and crystal growth methodologies, innovative characterisation techniques and unusual drug delivery methods are covered.