well, he made sure he had 3–4 measurements either side of the melting line as well as
two at the equilibrium where there was part melt of the sample. This procedure was
repeated at various pressures. In his paper in 1914, he explored the melting curves of
11 substances ranging from simple elements (potassium) to more complex molecular
systems such as aniline and o-cresol that has laid the groundwork for more recent
evaluations of these systems through diffraction methods [21, 22, 63]. In the 1940s
he continued to explore hundreds of more compounds in a series of papers after the
development of new pieces of apparatus.
More recent developments in the area have been made by Dziubek and Katrusiak
and our own work together with the Kamenev group and developments at ISIS. The
work of Dziubek and Katrusiak developed apparatus capable of investigating the
compression of materials on a large scale [19]. Their simple and effective piston
design allows for the change in volume to be measured as a function of the applied
load. In this set-up there is no control over sample temperature so increases in heat
through adiabatic routes have to be minimised through small pressure increments.
The body of the cell is large enough that the heat can be dissipated relatively easily.
The effectiveness of the press was demonstrated using a number of simple organic
compounds where (1) the phase transition was easily observed, e.g. chloroform,
3-aminopropan-1-ol and 1-methyl-benzoate, and (2) the phase transition was
supressed by the large molecular rearrangement required from Phase I to Phase II,
e.g. imidazole, akin to that observed for aniline [22] and 2-methylphenol [21].
In collaboration with the Kamenev group at the University of Edinburgh, we have
built on previous work of the Pulham group and developed the use of our own large
volume press (Fig. 6). Pulham and co-workers investigated the recovery of highpressure forms to ambient pressure in quantities sufficient for characterisation at
ambient pressure. The recovery or quenching of materials is particularly significant
for fine chemicals, including pharmaceuticals, due to the potential for polymorphism
in these systems. Polymorph screening is a vital technique to solid-form discovery,
and it is conducted at ambient pressure by variation in solvent system, method of
crystallisation, grinding, temperature, etc. By use of a large volume press for
recovery, the program of discovery becomes far more extensive, and confidence in
phase stability can be increased. Pulham and co-workers were able to use a large
volume press, previously used to enhance Diels-Alder cycloaddition reactions for
poorly reacting dienophiles [64], to produce the metastable orthorhombic form of
paracetamol and recover it in gram quantities to ambient pressure through cooling
for analysis using neutron diffraction [43]. We have continued to investigate the
quenching of materials using this press and have successfully demonstrated that it
can be achieved using exemplar systems of glycolide [65] and p-aminobenzoic
acid [66].
To develop the methodology further, we have recently investigated the use of
anti-solvent addition at high pressure using the large volume press. Nucleation is one
of the major challenges when investigating liquids or solutions under high-pressure
conditions; hence, methodologies that can improve and reproducibly initiate nucleation are a significant development. Anti-solvent addition is common practice in
crystallisation methodologies at ambient pressure, but our ability to do this in a DAC
156
S. A. Moggach and I. D. H. Oswald
two at the equilibrium where there was part melt of the sample. This procedure was
repeated at various pressures. In his paper in 1914, he explored the melting curves of
11 substances ranging from simple elements (potassium) to more complex molecular
systems such as aniline and o-cresol that has laid the groundwork for more recent
evaluations of these systems through diffraction methods [21, 22, 63]. In the 1940s
he continued to explore hundreds of more compounds in a series of papers after the
development of new pieces of apparatus.
More recent developments in the area have been made by Dziubek and Katrusiak
and our own work together with the Kamenev group and developments at ISIS. The
work of Dziubek and Katrusiak developed apparatus capable of investigating the
compression of materials on a large scale [19]. Their simple and effective piston
design allows for the change in volume to be measured as a function of the applied
load. In this set-up there is no control over sample temperature so increases in heat
through adiabatic routes have to be minimised through small pressure increments.
The body of the cell is large enough that the heat can be dissipated relatively easily.
The effectiveness of the press was demonstrated using a number of simple organic
compounds where (1) the phase transition was easily observed, e.g. chloroform,
3-aminopropan-1-ol and 1-methyl-benzoate, and (2) the phase transition was
supressed by the large molecular rearrangement required from Phase I to Phase II,
e.g. imidazole, akin to that observed for aniline [22] and 2-methylphenol [21].
In collaboration with the Kamenev group at the University of Edinburgh, we have
built on previous work of the Pulham group and developed the use of our own large
volume press (Fig. 6). Pulham and co-workers investigated the recovery of highpressure forms to ambient pressure in quantities sufficient for characterisation at
ambient pressure. The recovery or quenching of materials is particularly significant
for fine chemicals, including pharmaceuticals, due to the potential for polymorphism
in these systems. Polymorph screening is a vital technique to solid-form discovery,
and it is conducted at ambient pressure by variation in solvent system, method of
crystallisation, grinding, temperature, etc. By use of a large volume press for
recovery, the program of discovery becomes far more extensive, and confidence in
phase stability can be increased. Pulham and co-workers were able to use a large
volume press, previously used to enhance Diels-Alder cycloaddition reactions for
poorly reacting dienophiles [64], to produce the metastable orthorhombic form of
paracetamol and recover it in gram quantities to ambient pressure through cooling
for analysis using neutron diffraction [43]. We have continued to investigate the
quenching of materials using this press and have successfully demonstrated that it
can be achieved using exemplar systems of glycolide [65] and p-aminobenzoic
acid [66].
To develop the methodology further, we have recently investigated the use of
anti-solvent addition at high pressure using the large volume press. Nucleation is one
of the major challenges when investigating liquids or solutions under high-pressure
conditions; hence, methodologies that can improve and reproducibly initiate nucleation are a significant development. Anti-solvent addition is common practice in
crystallisation methodologies at ambient pressure, but our ability to do this in a DAC
156
S. A. Moggach and I. D. H. Oswald