Reflexions, the University of Liège website that makes knowledge accessible


Analysing the quality of drugs

10/12/15

Vibrational spectroscopy, which is a technique for revealing the chemical and physical properties of molecules, is a precious tool in the pharmaceutical sector. Researchers at the Analytical Chemistry Laboratory of the University of Liege who specialise in this area of research, regularly collaborate with pharmaceutical companies to check their raw materials, finished products and processes.

The term “vibrational spectroscopy” conjures up visions of an antiquated form of torture or perhaps even an endoscopy-like method for exploring our body cavities. Actually it is nothing of the sort: vibrational spectroscopy is a technique that provides chemical and physical information thanks to the analysis of vibrations of the matter being studied whether this involves molecules in solution or a solid. It is one of the main research subjects of the Analytical Chemistry Laboratory of the Pharmacy Department of the University of Liege directed by Professor Philippe Hubert whose research focusses on the quality of drugs from the raw materials stage to the finished product. “Three main avenues of research are pursued in the Analytical Chemistry Laboratory: the development, robust optimisation and validation of methods for analysing pharmaceutical and biological samples, chemometrics which consists of applying mathematical and statistical tools that make it possible to obtain a maximum amount of information from a large amount of data, and finally, vibrational imaging”, explains Doctor Eric Ziemons, who is a specialist in this latter field of research. “Vibrational spectroscopy has developed strongly since the beginning of the 2000s and is now very widely used in the pharmaceutical field for checking raw materials, finished products but also key stages in a process aimed at manufacturing products that conform to regulatory standards”, explains the researcher.

Medium infrared spectrum

Vibrating the molecules in order to expose them

There are three main techniques of vibrational spectroscopy known as mid-infrared (MIR), near-infrared (NIR) and Raman. In the context Process Analytical Technology (PAT), the first is used for more specific applications and the two others are often considered as being complementary. “Near-infrared spectroscopy is a technique that is very well-developed while that based on Raman scattering that is being currently developed offers advantages with regard to the interpretation of the signals obtained. It is also a very promising technique in the biotechnology sector”, explains Eric Ziemons.  Without going into the details of these different techniques, all three are based on the same principle: causing the vibration of the molecules in a sample to vibrate and gathering information on the chemical bonds of the molecules that it is composed of. “In this way we obtain two types of information: chemical and also physical characteristics (crystalline structure, size of the particles, hardness of a tablet)”, continues the specialist. “These techniques present important advantages with regard to traditional methods such as liquid chromatography. While analysis of a drug by the latter method takes several minutes, analysis by vibrational spectroscopy only takes 5 to 10 seconds and does not require preparation of the sample beforehand. Combined with imaging, it makes it possible to precisely map one or other compounds of the pharmaceutical matrix”, indicates Eric Ziemons. Another non-negligible advantage, particularly in the context of following procedures or in the fight against drug counterfeiting: vibrational spectroscopy is a non-destructive method. The sample analysed can therefore be recovered to be subjected to other analyses.

Pharmaceutical analysisPharma analysis RAMAN

Complex signals difficult to interpret

If the positive aspects of the use of vibrational spectroscopy are undeniable, this method also has some drawbacks. “The signal it supplies is very complex to interpret. It provides much chemical and physical information for all the compounds of the analysed matrix. Very sophisticated chemometric tools are therefore required to exploit this information and extract the information that is of interest to us”, explains Eric Ziemons. “The use of chemometrics therefore requires extra expertise in order to be able to interpret the results”. Another drawback of near-infrared and Raman spectroscopy is that they do not enable detection of compounds whose content is less than 1%.

Not perfect but sufficiently convincing, the vibrational techniques have convinced the pharmaceutical industry and many firms have used these techniques to control their raw materials, products and processes. The Analytical Chemistry Laboratory of the University of Liege regularly collaborates with pharmaceutical companies seeking expertise in this area. Lastly, in collaboration with the company UCB, Pierre-François Chavez, a doctoral student at the laboratory focussed on the implementation of vibrational spectroscopy to control a drug produced by the company. His work was aimed at improving the quality of a tablet with the help of an approach based on the “Design Space”, near-infrared spectroscopy and Raman imaging. The results of this study were recently published in the International Journal of Pharmaceutics (1).  

In the context of this same collaboration between the researchers from Liege and UCB, a second study was also published in Talanta (2). The aim of this work was to follow the content of active ingredient, that is to say the therapeutic compounds in the tablets during their production. “The results of this study demonstrate the relevance and analytical performances of near-infrared spectroscopy as a “PAT” tool for controlling the content of active ingredient of the tablets during the compression stage”, reveals Eric Ziemons.

Active ingredients drugs

In order to further develop the techniques of vibrational spectroscopy in the Analytical Chemistry Laboratory, the researcher aims to improve data processing. “We are capable of following procedures, but for now we do not have statistical tools which make it possible to guarantee the control of the data processing”, explains the scientist. “We would like to develop a more efficient control strategy in terms of information processing, capable of defining thresholds and alerts in order to correct the deviations observed in a process”.

Infrared paracetamol Analysis

Handheld analyzers for field analysis

Eric Ziemons and his team also plan to concentrate their efforts on portable vibrational spectroscopy systems. “These are being actively developed and greatly interest the different actors in the pharmaceutical sector in the context of field analysis”, explains the specialist. “They make it possible to carry out first line analyses and therefore to more easily choose other more thorough analysis methods”. More specifically, the first priority of the Analytical Chemistry Laboratory is to improve the processing of the data collected and thereafter the portable systems with a view to more effectively combatting the counterfeiting of medicines (see article: ).

(1) Chavez PF, Lebrun P, Sacré PY, De Bleye C, Netchacovitch L, Cuypers S, Mantanus J, Motte H, Schubert M, Evrard B, Hubert P, Ziemons E. Optimization of a Pharmaceutical Tablet Formulation based on a Design Space Approach and using Vibrational Spectroscopy as PAT Tool. Int J Pharm., 486, 2015, 13-20. doi: 10.1016/j.ijpharm.2015.03.025.
(2) Chavez PF, Sacré PY, De Bleye C, Netchacovitch, Mantanus J, Motte H, Schubert M, Hubert P, Ziemons E, Active Content Determination of Pharmaceutical Tablets using Near Infrared Spectroscopy as Process Analytical Technology Tool, Talanta 144, 2015, 1352-1359. doi :10.1016/j.talanta.2015.08.018


© Universit� de Li�ge - https://www.reflexions.uliege.be/cms/c_400033/en/analysing-the-quality-of-drugs?printView=true - March 28, 2024