SOLID STATE PHARMACEUTICAL CLUSTER:Crystallisation is a process which still holds some mystery. By increasing our understanding and creating more home-grown experts, Ireland's pharmaceutical industry is set for a boost

A SECRET AMONG scientists is that, under the microscope, even the most perfunctory of objects can become beautiful.

This is particularly true of medicines. Those in powdered and tablet forms are composed of crystals, and many types can be found within a single medicine.

Funded by SFI, the Solid State Pharmaceutical Cluster (SSPC) is seeking to optimise the way in which crystals, or the solid states, are produced, as well as developing new methods.

This cluster brings together five academic institutions (UL, TCD, UCD, UCC and NUIG) and nine pharmaceutical companies, including Janssen Pharmaceutical, Schering Plough, Eli Lily, GlaxoSmithKline, Merck Sharpe & Dohme, Roche Ireland, Pfizer, Covidien, and Helsinn Chemicals Ireland.

The cluster is led by Prof Kieran Hodnett of the University of Limerick (UL), who says "most people will take a tablet for something at some stage".

Hodnett explains that it takes a significant amount of technology to make a tablet, as they have complex components.

"As well as the active pharmaceutical ingredient, which is usually only a small part of the total make-up, there are many other ingredients that determine the speed at which the tablet is absorbed."

These ingredients are solid materials that, to the naked eye, resemble white powders. "A closer look at many of these under the microscope reveals very defined crystals," says Hodnett.

Crystallisation is the process by which these ingredients are created, whereby a super-saturated solution of an active ingredient is made via chemical synthesis and then crystallised to form a powder.

"The active ingredient of the tablet then comes out in a crystallisation stent. The stent has to be very productive, as you want to get as much of the molecule out of the solution and into the solid form as possible," explains Hodnett.

The objective of the SSPC is to design solid-state pharmaceutical materials in the required physical and chemical forms to meet the demands of advanced formulation and drug delivery systems.

As one of the most highly regulated industries, the pharmaceutical sector has significant and costly problems with the lack of reproducibility of solid-state forms, adds Hodnett.

As well as optimising the above process, in addition, the SSPC are also looking at elucidating the very basics of the process, which as yet still aren't fully understood, he also admits.

"One of the big issues for us, going from doing a crystallisation on a small scale to doing it in a plant, is that the behaviour tends to be completely different, depending on the scale at which it's done.

"Compared to a beaker in the lab, it is much more difficult to cool down a very large mass of solution."

Understanding the relationship between behaviour and scale is one of the major objectives of the cluster, he acknowledges.

The SSPC intends to comprehensively investigate pharmaceutical solids by bringing together complementary academic and industrial groupings from the disciplines of chemistry, pharmaceutics, pharmaceutical technology, chemical engineering and mechanical engineering.

Within these groups, there is expertise in process modelling and design, scale-up, computational fluid dynamics, in situ solution and solid-phase monitoring, crystallography and powder characterisation.

To this end there are over 60 people working within the cluster across the five institutes, Hodnett says.

Among those working in it are postgraduate researchers, postdoctoral researchers, as well as employees of the industry partners.

The companies involved are very happy with the development of the cluster, he adds."They feel that there hasn't been as much support in Irish universities for this particular area as there has been for other areas."

The founders of the cluster knew they had identified a gap in the market, and nine out of the 10 companies that they approached agreed to participate.

"We though we might get three or four, but were amazed that nine agreed to become involved," Hodnett admits.

Following recent trends in research, the companies are providing both manpower and machinery.

"They are sending people to us and also providing opportunities for our students to go to their labs."

While Ireland has a wealth of expertise in organic synthesis, expertise in crystallisation processes has been lacking.

An improvement in this will mean that many of the pharmaceutical giants that have bases in Ireland will be anchored here by the expertise, adds Hodnett.

"We are trying to increase the number of people in Ireland who would be experts in that area.

"One of the most important things for Ireland in the pharmaceutical arena is to continue to be the preferred choice and best possible site for manufacturers."