Chemicals Behaving Badly Programme Finds That Infra Red Spotlights Crystal Growth

Main Category: Biology / Biochemistry
Also Included In: Pharma Industry / Biotech Industry
Article Date: 22 Jan 2009 - 6:00 PDT

email to a friend   printer friendly   view / write opinions

The creation of a reproducible crystallisation process is a fundamental challenge to drug manufacturers, but a technique which provides real time detailed analyses of chemical processes could provide an answer.

Developed by engineers at the University of Leeds, the technique uses infra-red spectroscopy to monitor supersaturation - the levels of chemical saturation in a liquid - required for crystallisation to begin to occur.

Most drug compounds are crystalline, manufactured in batch process systems. Small changes in crystallisation process conditions, such as temperature and cooling rates, can significantly affect the structure of the resulting crystals, something which affects both their physical properties and their performance.

"For example, when you cool water the molecules in the water have to get into the right position to begin crystallising into ice crystals and the temperature can have a bearing on the size of ice crystals that are formed," says Dr Tariq Mahmud from the University's School of Process, Environmental and Materials Engineering. "It's similar with chemicals, although there's a wider range of parameters to take into account."

The new technique uses a probe attached to an infra-red spectrometer to measure the concentration of a specific chemical in solution. In laboratory experiments, this technique was used on the batch cooling crystallisation of chemical L-Glutamic acid (LGA). The information gained from the infra-red spectrometer is coupled with detailed statistical - or chemometric - data to provide a more detailed analysis of the crystallisation process than has been possible with other infra-red spectrometry techniques.

Dr Mahmud explains: "Using a chemometric approach enables us to take many more parameters into account, which makes it a more reliable predictor of the optimum concentration levels required to produce a particular crystal structure."

The latest technique was developed by engineers at Leeds in collaboration with researchers at Newcastle and Heriot-Watt universities as part of the Chemicals Behaving Badly programme which is funded by the Engineering and Physical Sciences Research Council, along with ten industrial partners.

It is the latest in a raft of new "Quality by Design" (QBD) tools being developed for the pharmaceutical manufacturing sector as part of a drive for increased understanding of drug processing fundamentals. "By developing tools to increase knowledge about, and monitor, batch process systems, we're providing practical solutions to problems faced by industry on a daily basis," says Dr Mahmud. "This sort of technological approach to manufacture will help reduce waste - and therefore costs - and could have a significant role to play in increasing the competitiveness of the pharmaceutical sector."

Notes:

1. This research is published in a paper entitled "In situ Measurement of Solution Concentration during the Batch Cooling Crystallisation of L-Glutamic Acid using ATR-FTIR Spectroscopy Coupled with Chemometrics". The paper has been published online in Crystal Growth & Design.

2. This work was draws on previous research and experimental systems developed through the Chemicals Behaving Badly II initiative. Led by Professor Kevin J Roberts at the University of Leeds, Chemicals Behaving Badly is an Engineering and Physical Sciences Research Council (EPSRC) and industrial consortium which includes the universities of Leeds, Heriot-Watt and Newcastle, along with ten key industrial partners. It is primarily concerned with optimal design of batch reactors using in-process measurement and advanced modelling techniques. It works in measurement and modelling across the length scales relevant to pharmaceutical and organic fine chemical production. 3. The Faculty of Engineering at the University of Leeds comprises five Schools: Civil Engineering; Computing; Electronic and Electrical Engineering; Mechanical Engineering and Process, Materials and Environmental Engineering. The 2008 Research Assessment Exercise (RAE) ranked the Faculty 7th in the UK overall, with 75% of its activity rated as 'internationally excellent' or 'world leading'. There are approximately 3,000 students in the Faculty, 80% undergraduates and 20% postgraduates. Two-thirds of our students are from the UK with the remainder representing over 90 different nationalities.

4. The University of Leeds is one of the largest higher education institutions in the UK with more than 30,000 students from 130 countries. With a turnover of £450m, Leeds is one of the top ten research universities in the UK, and a member of the Russell Group of research-intensive universities.

The Engineering and Physical Sciences Research Council (EPSRC) is the UK's main agency for funding research in engineering and the physical sciences. The EPSRC invests around £800 million a year in research and postgraduate training, to help the nation handle the next generation of technological change. The areas covered range from information technology to structural engineering, and mathematics to materials science. This research forms the basis for future economic development in the UK and improvements for everyone's health, lifestyle and culture. EPSRC also actively promotes public awareness of science and engineering. EPSRC works alongside other Research Councils with responsibility for other areas of research. The Research Councils work collectively on issues of common concern via Research Councils UK. http://www.epsrc.ac.uk/

Source: Clare Elsley
University of Leeds