References of "Sacré, Pierre-Yves"
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See detailData processing of vibrational chemical imaging for pharmaceutical applications.
Sacre, Pierre-Yves ULg; De Bleye, Charlotte ULg; Chavez, Pierre-François ULg et al

in Journal of Pharmaceutical & Biomedical Analysis (in press)

Vibrational spectroscopy (MIR, NIR and Raman) based hyperspectral imaging is one of the most powerful tools analyze pharmaceutical preparation. Indeed, it combines the advantages of vibrational ... [more ▼]

Vibrational spectroscopy (MIR, NIR and Raman) based hyperspectral imaging is one of the most powerful tools analyze pharmaceutical preparation. Indeed, it combines the advantages of vibrational spectroscopy to imaging techniques and allows therefore the visualization of distribution of compounds, crystallization processes. However, these techniques provide a huge amount of data that must be processed to extract the relevant information. This review presents fundamental concepts of hyperspectral imaging, the basic theory of the most used chemometric tools used to pre-process, process and post-process the generated data. The last part of the present paper focuses on pharmaceutical applications of hyperspectral imaging and highlights the data processing approaches to enable the reader making the best choice among the different tools available. [less ▲]

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See detailAnalytical strategies for the detection of counterfeit erectile dysfunction drugs.
Sacre, Pierre-Yves ULg; Deconinck, Eric; De Beer, Jacques

in Wang, Perry; Wertheimer, Albert (Eds.) Counterfeit Medicines Volume II: Detection, Identification and Analysis (in press)

Among all classes of drugs, the type 5 phosphodiesterase inhibitors (PDE5-i) (sildenafil, vardenafil and tadalafil) are the most counterfeited and copied in industrialized countries. This is why it is ... [more ▼]

Among all classes of drugs, the type 5 phosphodiesterase inhibitors (PDE5-i) (sildenafil, vardenafil and tadalafil) are the most counterfeited and copied in industrialized countries. This is why it is very important for regulatory agencies to have a panel of analytical methods to analyse these drugs and to be able to detect counterfeit or substandard medicines. During this chapter, several analytical techniques will be described and discussed. Among spectroscopic techniques, Raman, NIR, FT-IR and chemical imaging techniques will be envisaged. Their ability to detect counterfeits and predict if a new sample is genuine or not will be presented. Other techniques such as XRay powder diffraction and NMR spectroscopies will be briefly presented. Chromatographic impurity fingerprints will be considered and described for the analysis of suspect samples of Cialis® and Viagra®. Once again, the possibility to predict the authenticity of a new sample by the mean of this technique is envisaged. Finally, a MS-compatible UHPLC-UV method for the analysis of the three authorised PDE5-i and some of their analogues will be shortly described. This technique has been validated using spiked placebo samples in a vegetal matrix representing a suspect sample with a complex matrix. As a conclusion, a generic strategy for the detection and quality evaluation of counterfeit drugs will be presented. [less ▲]

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See detailDevelopment of a quantitative approach using surface-enhanced Raman chemical imaging: First step for the determination of an impurity in a pharmaceutical model
De Bleye, Charlotte ULg; Sacre, Pierre-Yves ULg; Dumont, Elodie ULg et al

in Journal of Pharmaceutical & Biomedical Analysis (2014), 90

This publication reports, for the first time, the development of a quantitative approach using surface-enhanced Raman chemical imaging (SER-CI). A pharmaceutical model presented as tablets based on ... [more ▼]

This publication reports, for the first time, the development of a quantitative approach using surface-enhanced Raman chemical imaging (SER-CI). A pharmaceutical model presented as tablets based on paracetamol, which is the most sold drug around the world, was used to develop this approach. 4-Aminophenol is the main impurity of paracetamol and is actively researched in pharmaceutical formulations because of its toxicity. As its concentration is generally very low (<0.1%, w/w), conventional Raman chemical imaging cannot be used. In this context, a SER-CI method was developed to quantify 4-aminophenol assessing a limit of quantification below its limit of specification of 1000 ppm. Citrate-reduced silver nanoparticles were used as SERS substrate and these nanoparticles were functionalized using 1-butanethiol. Different ways to cover the tablets surface by butanethiol-functionalized silver nanoparticles were tested and a homogeneity study of the silver nanoparticles covering was realized. This homogeneity study was performed in order to choose the best way to cover the surface of tablets by silver colloid. Afterwards, the optimization of the SER-CI approach was necessary and different spectral intensity normalizations were tested. Finally, a quantitative approach using SER-CI was developed enabling to quantify 4-aminophenol from 0.025% to 0.2% in paracetamol tablets. This quantitative approach was tested on two different series of tablets using different batches of silver nanoparticles. [less ▲]

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See detailQuantitative approaches based on Surface-Enhanced Raman Scattering (SERS) and Surface-Enhanced Raman Chemical Imaging (SER-CI)
De Bleye, Charlotte ULg; Sacre, Pierre-Yves ULg; Dumont, Elodie ULg et al

Conference (2014, January 20)

Surface-enhanced Raman scattering (SERS), discovered in 1978, is a recent technique enabling to circumvent the main limitations of classical Raman spectroscopy by dramatically exalting the Raman ... [more ▼]

Surface-enhanced Raman scattering (SERS), discovered in 1978, is a recent technique enabling to circumvent the main limitations of classical Raman spectroscopy by dramatically exalting the Raman scattering of the target molecules which are adsorbed or very closed to metallic surfaces while reducing the fluorescence impact on spectra [1]. This technique combines the sensitivity of the fluorescence keeping the structural information of molecules obtained from the SERS spectrum [2]. This last point allows to implement multiplex analyses. Moreover, it is possible to perform Surface-enhanced Raman chemical imaging (SER-CI) analyses which enable to acquire a visual representation of samples combining spectral and spatial measurements. Therefore SERS could become an attractive technique in numerous fields such as pharmaceutical and biomedical research. In this context, the feasibility of developing quantitative approaches using SERS and SER-CI on a pharmaceutical model was studied. The aim was to develop methods allowing the quantification of 4-aminophenol (4-AP) in a pharmaceutical formulation based on paracetamol. 4-AP is the main impurity of paracetamol and is actively research because of its toxicity. This pharmaceutical model was first investigated using SERS and a quantitative method enabling to quantify 4-AP from 3 to15 µg/mL was developed and validated using the standard addition method as a calibration method [3]. From these results, the possibility of developing a quantitative approach using SER-CI was investigated. Tablets based on paracetamol comprising different concentrations of 4-AP were prepared. Different ways to cover the sample surface by the SERS substrate were tested and a homogeneity study was performed to improve the repeatability of SER-CI analyses. Different spectral intensity normalizations were also tested in order to optimize the SER-CI method. Finally, a quantitative approach using SER-CI was developed allowing the quantification of 4-AP from 0.025% to 0.2% (w/w) in paracetamol tablets [4]. This first quantitative approach could pave the way to quantitative analysis of small molecules using SER-CI in complex matrices. References [1] P.L. Stiles, J.A. Dieringer, N.C. Shah, R.P. Van Duyne, Annu. Rev. Anal. Chem. 1 (2008) 601-626. [2] R.F. Aroca, R.A. Alvarez-Puebla, N. Pieczonka, S. Sanchez-Cortez, J.V. Garcia-Ramos, Adv. Colloid Interface Sci. 116 (2005) 45-61. [3] C. De Bleye, E. Dumont, E. Rozet, P.-Y. Sacré, P.-F. Chavez, L. Netchacovitch, G. Piel, Ph. Hubert, E. Ziemons, Talanta 116 (2013) 899-905. [4] C. De Bleye, P.-Y. Sacré, E. Dumont, L. Netchacovitch, P.-F. Chavez, G. Piel, P. Lebrun, Ph. Hubert, E. Ziemons, J. Pharm. Biomed. Anal. (in Press) [less ▲]

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See detailA new criterion to assess distributional homogeneity in hyperspectral images of solid pharmaceutical dosage forms
Sacre, Pierre-Yves ULg; Lebrun, Pierre ULg; Chavez, Pierre-François ULg et al

in Analytica Chimica Acta (2014), 818

During galenic formulation development, homogeneity of distribution is a critical parameter to check since it may influence activity and safety of the drug. Raman hyperspectral imaging is a technique of ... [more ▼]

During galenic formulation development, homogeneity of distribution is a critical parameter to check since it may influence activity and safety of the drug. Raman hyperspectral imaging is a technique of choice for assessing the distributional homogeneity of compounds of interest. Indeed, the combination of both spectroscopic and spatial information provides a detailed knowledge of chemical composition and component distribution. Actually, most authors assess homogeneity using parameters of the histogram of intensities (e.g. mean, skewness and kurtosis). However, this approach does not take into account spatial information and loses the main advantage of imaging. To overcome this limitation, we propose a new criterion: Distributional Homogeneity Index (DHI). DHI has been tested on simulated maps and formulation development samples. The distribution maps of the samples were obtained without validated calibration model since different formulations were under investigation. The results obtained showed a linear relationship between content uniformity values and DHI values of distribution maps. Therefore, DHI methodology appears to be a suitable tool for the analysis of homogeneity of distribution maps even without calibration during formulation development. [less ▲]

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See detailDetermination of 4-aminophenol in a pharmaceutical formulation using Surface Enhanced Raman scattering: from development to method validation
De Bleye, Charlotte ULg; Dumont, Elodie ULg; Rozet, Eric ULg et al

in Talanta (2013), 116

A Surface Enhanced Raman Scattering (SERS) method able to quantify 4-aminophenol in a pharmaceutical formulation based on acetaminophen, also called paracetamol, was developed and, for the first time ... [more ▼]

A Surface Enhanced Raman Scattering (SERS) method able to quantify 4-aminophenol in a pharmaceutical formulation based on acetaminophen, also called paracetamol, was developed and, for the first time, successfully validated. In this context, silver nanoparticles were synthesized according to the method described by Lee-Meisel and used as SERS substrate. The repeatability of the silver colloid synthesis was tested using different methods to characterise the size and the zeta potential of silver nanoparticles freshly synthesized. To optimize the SERS samples preparation, a design of experiments implicating concentrations of citrate-reduced silver nanoparticles and aggregating agent was performed in order to maximize the Raman signal enhancement. Finally, an approach based on tolerance intervals and accuracy profiles was applied in order to thoroughly validate the method in a range of concentrations comprised from 3 to 15 µg mL-1 using normalized band intensities. The standard addition method was selected as method calibration. Therefore, measurements were carried out on 4-aminophenol spiked solutions of the pharmaceutical formulation. Despite the well-known stability and reproducibility problems of SERS, the validation was performed using two operators and 5 batches of nanoparticles, one for each validation day. [less ▲]

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See detailDevelopment of a quantitative approach based on surface-enhanced Raman chemical imaging (SER-CI)
De Bleye, Charlotte ULg; Sacre, Pierre-Yves ULg; Dumont, Elodie ULg et al

Conference (2013, October 17)

During the last decade, Raman imaging has taken an important place in the pharmaceutical field [1-2]. It enables to acquire a visual representation of samples while quantifying and identifying molecules ... [more ▼]

During the last decade, Raman imaging has taken an important place in the pharmaceutical field [1-2]. It enables to acquire a visual representation of samples while quantifying and identifying molecules of these samples. However, this technique suffers from a lack of sensitivity and the appearance of fluorescence which can limit its pharmaceutical applications. One way to circumvent these limitations is Surface Enhanced Raman chemical imaging (SER-CI) which presents the advantages of Raman imaging and enables to dramatically increase the Raman scattering of molecules adsorbed or very close to metallic surfaces [3]. The number of publications regarding SER-CI in the pharmaceutical field is very limited probably due to the well-known stability and reproducibility problem of SERS and also due to the difficulty to obtain a homogeneous colloids covering of samples surface before SER-CI analyses. In this context, the possibility to develop a quantitative approach using SER-CI on a pharmaceutical model, presented as paracetamol tablet, was studied. The aim was to develop a SER-CI method enabling to quantify 4-aminophenol (4-AP), which is the main impurity of paracetamol actively research for its toxicity, at a concentration below its limit of specification of 1000 ppm [4]. This pharmaceutical model was first investigated using SERS and a quantitative method enabling to quantify 4-AP from 3 to 15 µg mL-1 was developed and validated [5]. Based on these previous results, the possibility to develop quantitative approach to quantify 4-aminophenol in paracetamol tablet using SER-CI was investigated. Different ways to cover the tablets surface by silver colloids were tested and a homogeneity study was performed in order to improve the repeatability of SER-CI analyses. Afterwards, the SER-CI approach was optimized and different spectral intensity normalizations were tested. Finally, a quantitative approach using SER-CI was developed enabling to quantify 4-AP from 0.025% to 0.2% (w/w) in paracetamol tablets. [less ▲]

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See detailVibrational spectroscopy as PAT compliant tools
Ziemons, Eric ULg; De Bleye, Charlotte ULg; Chavez, Pierre-François ULg et al

Scientific conference (2013, September 10)

In the last decades, intensive research and development dealing with NIR and Raman spectroscopy have taken place in industrial field, espacially in pharmaceutical industry. This enthusiasm can be ... [more ▼]

In the last decades, intensive research and development dealing with NIR and Raman spectroscopy have taken place in industrial field, espacially in pharmaceutical industry. This enthusiasm can be explained by the fact that this technique are regarded as promising and attractive tools in PAT, R&D and Green Chemistry frameworks. Their advantages such as non-invasive, non-destructive, fast data acquisition, minization of sample preparation step and the use of probes in on-line, in-line and at-line are expected to reach the aims of PAT, R&D and Green Chemistry. [less ▲]

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See detailA new criterion to assess distributional homogeneity in hyperspectral images of solid pharmaceutical dosage forms
Sacre, Pierre-Yves ULg; Lebrun, Pierre ULg; Chavez, Pierre-François ULg et al

Conference (2013, September)

During galenic formulation development, homogeneity of distribution is a critical parameter to check since it may influence activity and safety of the drug. Several techniques exist to assess this ... [more ▼]

During galenic formulation development, homogeneity of distribution is a critical parameter to check since it may influence activity and safety of the drug. Several techniques exist to assess this homogeneity, the most used and recognized being HPLC. However, these techniques are destructive, time consuming and uses a lot of organic solvents. Vibrational spectroscopies are promising green chemistry techniques that may replace HPLC for several analysis tasks thanks of their rapid, non-destructive and non-pollutant characteristics. Raman hyperspectral imaging is a technique of choice for assessing the distributional homogeneity of compounds of interest. Indeed, the combination of both spectroscopic and spatial information provides a detailed knowledge of chemical composition and component distribution. When dealing with hyperspectral imaging, multivariate data analysis is necessary to extract the concentration map of the compound of interest that will be used to assess sample homogeneity. Actually, most authors assess homogeneity using parameters of the histogram of intensities (e.g. mean, skewness and kurtosis). However, this approach does not take into account spatial information and loses the main advantage of imaging. Recently, Rosas et al. proposed a homogeneity index based on the Poole index. However, it necessitates cutting the maps in non-overlapping macropixels and is therefore quickly limited with small maps. To overcome this limitation, we propose a new criterion that combines Continuous Level Moving Blocks and homogeneity curves with a randomization step to assess the distributional homogeneity. This distributional homogeneity index (DHI) enables analysis of hyperspectral maps without apriori knowledge. It has been applied on five pharmaceutical formulations with different blending conditions. The uniformity content values of the API (present at a concentration of 7% w/w) measured by HPLC ranged from RSD: 0.46% to 11.04%. Ten tablets per formulation have been mapped over a region of interest of 4 mm². After extracting pure spectra by MCR-ALS, the concentration maps of the API were computed using classical least squares analysis. DHI have been computed with a hundred simulations for the randomization step for each concentration map. Afterwards, a mean DHI and standard deviation values were computed per formulation. A linear relationship has been observed between the RSD values and the mean DHI. These results enabled us to select the formulation with the best homogeneity. Further experiments are in progress to check whether hyperspectral imaging combined with DHI could be used in routine to assess blending homogeneity of well-known formulations. [less ▲]

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See detailChemical imaging of small molecules from simple to complex matrices: Quantitative approaches based on Surface Enhanced Raman scattering
De Bleye, Charlotte ULg; Sacre, Pierre-Yves ULg; Chavez, Pierre-François ULg et al

Conference (2013, July)

Surface Enhanced Raman scattering (SERS) allows to dramatically exalt the Raman diffusion of molecules absorbed or very closed to rough metallic surfaces while keeping their structural information. SERS ... [more ▼]

Surface Enhanced Raman scattering (SERS) allows to dramatically exalt the Raman diffusion of molecules absorbed or very closed to rough metallic surfaces while keeping their structural information. SERS chemical imaging, presenting a high specificity and sensibility, allows acquiring a visual representation of samples combining spectral and spatial measurements. This technique could become a powerful tool in pharmaceutical and biological analysis enabling to identify and quantify molecules thanks to chemometric evaluation while looking at their distribution or their interactions. In this context, SERS chemical imaging is investigated in detection or quantitative determination of molecules in pharmaceutical and biological matrices. The feasibility of making quantitative measurements using SERS is evaluated on small target molecules models such as 4-aminophenol and lactate. Firstly, a SERS method to quantify 4-aminophenol which is the primary impurity of acetaminophen coming from its degradation during the storage or from its synthesis was developed on a real pharmaceutical formulation. The standard addition method was selected as calibration method in order to take into account the matrix effect coming from the different components of the latter. Despite the well-known stability and repeatability problems of SERS, the method was thoroughly validated by means of accuracy profiles as decision tool. Moreover, this validation methodology allowed to define a first estimation of the real analytical performance of the technique. Secondly, the detection of lactate, which is a critical metabolite implicated in several metabolic disorders, was successfully tested in the physiological concentration in a simple matrix. Preliminary results for the determination of this metabolic biomarker were also very promising allowing to consider more complex matrices. Based on these results, SERS chemical imaging was implemented to detect 4-aminophenol in a pharmaceutical tablet formerly pulverised by a SERS substrate. Through this imaging technique, it was not only possible to detect the presence of the impurity at the limit of specification of 0.1% (w/w) but it was also possible to differentiate tablets comprising different concentrations of the latter. These promising results represent the first step towards quantitative measurements using SERS chemical imaging. [less ▲]

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See detailEvaluation of the residual solvent content of counterfeit tablets and capsules
Deconinck, Eric; Canfyn, Michael; Sacre, Pierre-Yves ULg et al

in Journal of Pharmaceutical & Biomedical Analysis (2013), 81-82

A group of counterfeit samples of Viagra® and Cialis® were screened for their residual solvent content and compared to the content of the genuine products. It was observed that all counterfeit samples had ... [more ▼]

A group of counterfeit samples of Viagra® and Cialis® were screened for their residual solvent content and compared to the content of the genuine products. It was observed that all counterfeit samples had higher residual solvent contents compared to the genuine products. A more diverse range of residual solvents was found as well as higher concentrations. In general these concentrations did not exceed the international imposed maximum limits. Only in a few samples the limits were exceeded. A Projection Pursuit analysis revealed clusters of samples with similar residual solvent content, possibly enabling some future perspectives in forensic research. [less ▲]

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See detailValidation methodologies of near infrared spectroscopy methods in pharmaceutical applications
Chavez, Pierre-François ULg; De Bleye, Charlotte ULg; Sacre, Pierre-Yves ULg et al

in European Pharmaceutical Review (2013), 18(1), 3-6

As any analytical methods, a mandatory step at the end of the development of a near infrared spectroscopy (NIRS) method is the validation. This step enables to give enough guarantees that each future ... [more ▼]

As any analytical methods, a mandatory step at the end of the development of a near infrared spectroscopy (NIRS) method is the validation. This step enables to give enough guarantees that each future results coming from the application of the method in routine will be closed enough to the true value. However, from the literature, a minority of NIRS methods are thoroughly validated despite of the guidelines published by different group and regulatory authorities to help analyst to adequately decide if his method can be considered as valid. In this context, the aim of this review is to offer a critical overview of the different validation methodologies applied to assess the validity of quantitative methods using near infrared spectroscopy used in the field of pharmacy. [less ▲]

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See detailChromatography in the detection and characterisation of illegal pharmaceutical preparations
Deconinck, Eric; Sacre, Pierre-Yves ULg; Courselle, Patricia et al

in Journal of Chromatographic Science (2013), 51(8), 791-806

Counterfeit and illegal pharmaceutical products are an increasing worldwide problem and constitute a major challenge for analytical laboratories to detect and characterize them. Spectroscopic techniques ... [more ▼]

Counterfeit and illegal pharmaceutical products are an increasing worldwide problem and constitute a major challenge for analytical laboratories to detect and characterize them. Spectroscopic techniques as infrared spectroscopy and Raman spectroscopy were always the first methods of choice to detect counterfeits and illegal preparations, but due to the evolution in the products seized and the necessity of risk assessment, chromatographic methods are becoming more important in this domain. This review intends to give a general overview of the techniques described in literature to characterize counterfeit and illegal pharmaceutical preparations, focussing on the role of chromatographic techniques, with different detection tools. [less ▲]

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See detailPAT tools for the control of co-extrusion implants manufacturing process
Krier, Fabrice ULg; Mantanus, Jérome; Sacre, Pierre-Yves ULg et al

in International Journal of Pharmaceutics (2013), 458

Hot melt extrusion is a novel pharmaceutical manufacturing process technique. In this study, we identified four Critical Quality Attributes (CQAs) of the implant manufacturing process by hot melt ... [more ▼]

Hot melt extrusion is a novel pharmaceutical manufacturing process technique. In this study, we identified four Critical Quality Attributes (CQAs) of the implant manufacturing process by hot melt extrusion: the implant diameter, the quantity of the Active Pharmaceutical Ingredient (API), the homogeneity distribution of API and the thickness of the membrane. We controlled the implant diameter and the quantity of API in-line with a laser measurement, NIR and Raman spectroscopy, respectively. These two different spectroscopic techniques provided comparable results. In fact, the RMSEC and RMSECV were very close in each PAT technique but NIR spectroscopy was easier to use and less sensitive to external changes. For the control of the homogeneity of API distribution and the thickness of the membrane, we used successfully Raman spectroscopy imaging. These PAT tools help reducing analysis time. [less ▲]

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