Pierre-Yves Sacré

University of Liège | ulg · Center for Interdisciplinary Research on Medicines

Near-infrared (NIR) spectroscopy is actually a well-established technique that demonstrates its performance in the frame of detection of poor-quality medicines. The use of low-cost handheld NIR spectrophotometers in low-resource contexts can allow an inexpensive and more rapid detection compared to laboratory methods. Considering these points, it w...

Quantitative structure-retention relationship models (QSRR) have been utilized as an alternative to costly and time-consuming separation analyses and associated experiments for predicting retention time. However, achieving 100 % accuracy in retention prediction is unrealistic despite the existence of various tools and approaches. The limitations of...

The negative consequences of Substandard and falsified (SF) medicines are widely documented nowadays and there is still an urgent need to find them in more efficient ways. Several screening tools have been developed for this purpose recently. In this study, three screening tools were used on 292 samples of ciprofloxacin and metronidazole collected...

As the pharmaceutical manufacturing industry is moving from batch-wise production to continuous production, concepts such as quality by design, continuous process verification, and real-time release testing are gaining importance. These approaches need real-time measurements of critical quality attributes (CQAs) of the processed matter. The technol...

Surface-enhanced Raman scattering (SERS) is a vibrational widely used technique thanks to its multiple advantages such as its high specificity and sensitivity. The Raman signal exaltation comes from the use of metallic nanoparticles (Nps) acting as antennas by amplifying the Raman scattering. Controlling the Nps synthesis is a major point for the i...

Ellagic acid is one of the most studied polyphenolic compounds due to its numerous promising therapeutic properties. However, this therapeutic potential remains difficult to exploit owing to its low solubility and low permeability, resulting in low oral bioavailability. In order to allow an effective therapeutic application of EA, it is therefore n...

Reversed-Phase Liquid Chromatography (RPLC) is a common liquid chromatographic mode used for the control of pharmaceutical compounds during their drug life cycle. Nevertheless, determining the optimal chromatographic conditions that enable this separation is time consuming and requires a lot of lab work. Quantitative Structure Retention Relationshi...

Quality is one of the essential components of medicines and needs to be ensured to preserve the population’s health. This can be achieved through post-marketing quality control of medicines and is one of the most important duties of national regulatory authorities. In collaboration with the Cameroonian National Drug Quality Control and Valuation La...

In the pharmaceutical field, and more precisely in quality control laboratories, robust liquid chromatographic methods are needed to separate and analyze mixtures of compounds. The development of such chromatographic methods for new mixtures can result in a long and tedious process even while using the design of experiments methodology. However, de...

The ultimate goal of a one-class classifier like the “rigorous” soft independent modeling of class analogy (SIMCA) is to predict with a certain confidence probability, the conformity of future objects with a given reference class. However, the SIMCA model, as currently implemented often suffers from an undercoverage problem, meaning that its observ...

Quality control is a fundamental and critical activity in the pharmaceutical industry that guarantees the quality of medicines. QC analyses are currently performed using several well-known techniques, mainly liquid and gas chromatography. However, current trends are focused on the development of new techniques to reduce analysis time and cost, to i...

Vibrational spectroscopic techniques, i.e., attenuated total reflectance infrared (ATR-IR), near infrared spectroscopy (NIRS) and Raman spectroscopy (RS), coupled with Partial Least Squares Regression (PLSR), were evaluated as cost-effective label-free and reagent-free tools to monitor water content in Levulinic Acid/L-Proline (LALP) (2:1, mol/mol)...

Glycosylation is considered a critical quality attribute of therapeutic proteins as it affects their stability, bioactivity, and safety. Hence, the development of analytical methods able to characterize the composition and structure of glycoproteins is crucial. Existing methods are time consuming, expensive, and require significant sample preparati...

Chemometrics applied to spectroscopic measurements such as near-infrared are gaining more and more importance for quality control of pharmaceutical products. Handheld near-infrared devices show great promise as a medicines quality screening technique for post-marketing surveillance. These devices are able to detect substandard and falsified medicin...

There is a rising interest in the modelling and predicting of chromatographic retention. The progress towards more complex and comprehensive models emphasized the need for broad reliable datasets. The present dataset comprises small pharmaceutical compounds selected to cover a wide range in terms of physicochemical properties that are known to impa...

Almost 60% of commercialized pharmaceutical proteins are glycosylated. Glycosylation is considered a critical quality attribute, as it affects the stability, bioactivity and safety of proteins. Hence, the development of analytical methods to characterise the composition and structure of glycoproteins is crucial. Currently, existing methods are time...

Multivariate curve resolution unmixing of hyperspectral imaging data can be challenging when low sources of variance are present in complex samples, as for minor (low-concentrated) chemical compounds in pharmaceutical formulations. In this work, it was shown how the reduction of hyperspectral imaging data matrices through the selection of essential...

The distributional homogeneity of chemicals is a key parameter of solid pharmaceutical formulations. Indeed, it may affect the efficacy of the drug and consequently its safety. Chemical imaging offers a unique insight enabling the visualisation of the different constituents of a pharmaceutical tablet. It allows identifying ingredients poorly distri...

Poor-quality medicines are the cause of many public health and socioeconomic problems. We conducted a review to acquire an overview of the situation concerning such medicines in Cameroon. Different searches were performed on databases from several websites of the WHO, the Ministry of Public Health of Cameroon, the Anti-Counterfeit Medicine Research...

The optimization of pharmaceutical bioprocesses suffers from several challenges like complexity, upscaling costs, regulatory approval, leading to the risk of delivering substandard drugs to patients. Bioprocess is very complex and requires the evaluation of multiple components that need to be monitored and controlled in order to attain the desired...

This chapter covers applications of small, miniature, and portable near‐infrared (NIR) spectrometers in process analytical technology (PAT) in pharmaceutical manufacturing. Continuous manufacturing needs the process to be designed and conceived as a single system. Real‐time monitoring of the process, and the insurance of the quality of the final pr...

The aim of the present study was to explore the feasibility of applying near-infrared (NIR) spectroscopy for the quantitative analysis of Δ⁹-tetrahydrocannabinol (THC) in cannabis products using handheld devices. A preliminary study was conducted on different physical forms (entire, ground and sieved) of cannabis inflorescences in order to evaluate...

Hyperspectral imaging has been widely used for different kinds of applications and many chemometric tools have been developed to help identifying chemical compounds. However, most of those tools rely on factorial decomposition techniques that can be challenging for large data sets and/or in the presence of minor compounds. The present study propose...

The main goal of this work was to test the ability of vibrational spectroscopy techniques to differentiate between different polymorphic forms of fluconazole in pharmaceutical products. These are mostly manufactured with fluconazole as polymorphic form II and form III. These crystalline forms may undergo polymorphic transition during the manufactur...

In recent decades, more than 15% of the antimalarials marketed in low- and middle-income countries have been of poor quality, in which quinoline derivatives and quinine-based formulations account for 21%. Near infrared spectroscopy (NIR) was chosen for its fast and inexpensive test properties as well as the ability of using handheld devices to moni...

The analysis of illicit drugs faces many challenges, mainly regarding the production of timely and reliable results and the production of added value from the generated data. It is essential to rethink the way this analysis is operationalised, in order to cope with the trend toward the decentralization of forensic applications. This paper describes...

Class-modelling methods aim to predict the conformity of new unknown samples with a single target class, using statistical decision rules built exclusively with objects of that class. This article introduces a novel class-modelling method for spectral data. The method uses the concept of β%-prediction band for functional data to classify spectra. T...

With the fast growth of bioanalytical surface-enhanced Raman scattering (SERS), analytical methods have had to adapt to the complex nature of biological samples. In particular, interfering species and protein adsorption onto the SERS substrates have been addressed by sample preparation steps, such as precipitation or extraction, and by smart SERS s...

The proliferation of falsified medicines can cause serious public health issues, particularly in the context of a global pandemic such as the actual COVID-19 pandemic. Our study involved eight chloroquine phosphate medicines seized in Cameroon, Democratic Republic of Congo and Niger during March and May 2020. These suspect samples were first analyz...

In this study, adipose-derived stem cells (ASCs) are used to produce 3D bone grafts. The safety and the feasibility of using these bone grafts have been already showed and quality controls are already implemented. However, a cheaper, fast and non-destructive technique is required to monitor the osteogenic differentiation process. Here, the use of R...

Nowadays, the use of functionalised surface-enhanced Raman scattering (SERS) substrates has become common. These surface modifying agents notably act as Raman reporters, as sensors of biological processes (pH, redox probes) or to increase the sensitivity and/or the specificity of SERS detections. However, the effects of the functionalisation agents...

This paper addresses the issue of pharmaceutical solid dosage form quantitation using handheld Raman spectrophotometers. The two spectrophotometers used are designed with different technologies: one allows getting a more representative sampling with the Orbital Raster Scanning technology and the other one allows setting acquisition parameters. The...

This study demonstrates, for the first time, the ability of surface-enhanced Raman chemical imaging (SER-CI) combined with multivariate analysis to detect low levels (0.1% (w/w)) of a polymorphic form in a pharmaceutical mixture. In the studied formulation, piroxicam was used as a model molecule to develop this approach. Piroxicam is a widely avail...

Handheld Raman spectroscopy is actually booming. Recent devices improvements aim at addressing the usual Raman spectroscopy issues: fluorescence with shifted‐excitation Raman difference spectroscopy (SERDS), poor sensitivity with surface enhanced Raman scattering (SERS) and information only about the sample surface with spatially offset Raman spect...

Over the last decade, the growth of the global pharmaceutical market has led to an overall increase of substandard and falsified drugs especially on the African market (or emerging countries). Recently, several methods using handheld/portable vibrational spectroscopy have been developed for rapid and on-field drug analysis. The objective of this wo...

The fast pace of changes occurring in the pharmaceutical world emphasizes the need for powerful technologies that allow checking the quality of pharmaceutical products. Infrared and Raman spectroscopies have shown great potentialities for drug analysis in the last decades and consequently caught the attention of the scientific world as well as of i...

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Hyperspectral imaging has shown a high potential to analyze falsifications of solid pharmaceutical products since the last decade. Thanks to the non-destructive, ecological and non-invasive properties, it is a preferred technique for these kinds of applications. Moreover, thanks to the spectroscopic properties, it is possible to detect as well orga...

This paper addresses the issue of pharmaceutical solid dosage form quantitation using handheld Raman spectrophotometers. The two spectrophotometers used are designed with different technologies: one allows getting a more representative sampling with the Orbital Raster Scanning technology and the other one allows setting acquisition parameters. The...

Background and objectives The kidney stone’s structure might provide clinical information in addition to the stone composition. The Raman chemical imaging is a technology used for the production of two-dimension maps of the constituents' distribution in samples. We aimed at determining the use of Raman chemical imaging in urinary stone analysis. M...

Topological analysis of sample 12. Gaps provide grey to black spots according to their depth, while the whiter zones are associated with more intense Raman signal. (TIF)

Topological analysis of sample 3. Gaps provide grey to black spots according to their depth, while the whiter zones are associated with more intense Raman signal. (TIF)

Topological analysis of sample 9. Gaps provide grey to black spots according to their depth, while the whiter zones are associated with more intense Raman signal. (TIF)

Surface-enhanced Raman chemical imaging (SER-CI) is a highly sensitive analytical tool recently used in the pharmaceutical field owing to the possibility to obtain high sensitivity along with spatial information. However, the covering method of the pharmaceutical samples such as tablets with metallic nanoparticles is a major issue for SER-CI analys...

The analysis of serum samples by surface-enhanced Raman spectroscopy (SERS) has gained ground over the last few years. However, the stabilisation of colloids by the proteins contained in these samples has restricted their use in common practice, unless antibodies or aptamers are used. Therefore, this work was dedicated to the development of a SERS...

Near-infrared (NIR) global quantitative models were evaluated for the moisture content (MC) determination of three different freeze-dried drug products. The quantitative models were based on 3822 spectra measured on two identical spectrometers to include variability. The MC, measured with the reference Karl Fischer (KF) method, were ranged from 0.0...

The development of a quantitative method determining the crystalline percentage in an amorphous solid dispersion is of great interest in the pharmaceutical field. Indeed, the crystalline Active Pharmaceutical Ingredient transformation into its amorphous state is increasingly used as it enhances the solubility and bioavailability of Biopharmaceutica...

Background: Poor quality antimalarial medicines still represent a threat to the public health, especially in Sub-Saharan Africa who bears a disproportionate share of the global burden of malaria. It is essential and urgent to strengthen mechanisms against counterfeit medicines. One of the approaches is regular market surveillance through quality c...

Surface-enhanced Raman spectroscopy (SERS) is a sensitive analytical tool used in the pharmaceutical field in recent years. SERS keeps all the advantages of classical Raman spectroscopy while being is more sensitive allowing its use for the detection and the quantification of low-dose substances contained in pharmaceutical samples. However, the ana...

Since the Food and Drug Administration (FDA) published a guidance based on the Process Analytical Technology (PAT) approach, real-time analyses during manufacturing processes are in real expansion. In this study, in-line Raman spectroscopic analyses were performed during a Hot-Melt Extrusion (HME) process to determine the Active Pharmaceutical Ingr...

Les médicaments contrefaits/falsifiés font partie des médicaments de qualité inférieure. Les informations précises sur l’ampleur de la problématique de ces médicaments sont insuffisantes et il y a peu d’études réalisées à l’échelle mondiale. Toutefois, dans de nombreux cas, ils se sont révélés très dangereux et préjudiciables à la santé publique. A...

The use of Near-infrared spectroscopy (NIRS) as a fast and non-destructive technique was employed for moisture content (MC) determination in Antibody-drug conjugates (ADCs) in replacement to Karl Fischer (KF) method. The lab analysis of ADCs, high potent medicines, should be performed in conditions ensuring the operator’s safety and using secured a...

A new application of surface-enhanced Raman scattering (SERS) in the field of plant material analysis is proposed in this study. The aim was to monitor the release of anatabine by methyl jasmonate (MeJa) elicited Bright Yellow-2 (BY-2) cells. Gold nanoparticles (AuNps) were used as SERS substrate. The first step was to study the SERS activity of an...

Plant root-knot nematode interaction studies are performed on several host plant models. Though root-knot nematodes interact with trees, no perennial woody model has been explored so far. Here we show that poplar (Populus tremula x P. alba) grown in vitro is susceptible to Meloidogyne incognita allowing this nematode to penetrate, to induce feeding...

Over recent decades, spreading environmental concern entailed the expansion of green chemistry analytical tools. Vibrational spectroscopy, belonging to this class of analytical tool, is particularly interesting taking into account its numerous advantages such as fast data acquisition and no sample preparation. In this context, near-infrared, Raman...

Nowadays, supercritical fluid chromatography is commonly presented as a promising alternative technique in the field of separation sciences. Nevertheless the selection of chromatographic conditions and sample preparation of pharmaceutical compounds remain a challenge and peak distortion was previously highlighted. The main objective of the present...

When developing a new formulation, the development, calibration and validation steps of analytical methods based on vibrational spectroscopy are time-consuming. For each new formulation, real samples must be produced and a “reference method” must be used in order to determine the Active Pharmaceutical Ingredient (API) content of each sample. To cir...

The aim of this study was to develop Near Infrared (NIR) methods to determine the active content of non-coated pharmaceutical tablets manufactured from a proportional tablet formulation. These NIR methods intend to be used for the monitoring of the active content of tablets during the tableting process. Firstly, methods were developed in transmissi...

Bisphenol A (BPA) is well known for its use in plastic manufacture and thermal paper production despite its risk of health toxicity as an endocrine disruptor in humans. Since the publication of new legislation regarding the use of BPA, manufacturers have begun to replace BPA with other phenolic molecules such as bisphenol F (BPF) and bisphenol B (B...

The aim of the present study was to optimize a tablet formulation using a quality by design approach. The selected methodology was based on the variation of the filler grade, taking into account the Particle Size Distribution (PSD) of Active Pharmaceutical Ingredient (API) in order to improve five Critical Quality Attributes (CQAs). Thus, a mixture...

Poor quality antimalarial drugs are one of the public’s major health problems in Africa. The depth of this problem may be explained in part by the lack of effective enforcement and the lack of efficient local drug analysis laboratories. To tackle part of this issue, two spectroscopic methods with the ability to detect and to quantify quinine dihydr...

Newly developed drugs often have poor bioavailability due to their poor water solubility (BCS class 2 drugs). It is therefore necessary to develop new strategies to enhance their solubility and their activity, among which, Self-Emulsifying Drug Delivery System (SEDDS). The efficacy of the drugs contained in these preparations is mainly affected by...

As serious but neglected public health problems, poor quality medicines, i.e. for antimalarial me-dicines, urged to be fought. One of the approaches is to consider the analytical chemistry and se-parative techniques. In this study, a generic liquid chromatographic method was firstly developed for the purpose of screening 8 antimalarial active ingre...

Since the last decade, more and more Active Pharmaceutical Ingredient (API) candidates have poor water solubility inducing low bioavailability. These molecules belong to the Biopharmaceutical Classification System (BCS) class II and IV. Thanks to Hot-Melt Extrusion (HME), it is possible to incorporate these candidates in pharmaceutical solid forms....

Nowadays, the circulation of poor quality medicines is becoming an alarming worldwide phenomenon with serious public health and socio-economic concerns. The situation is particularly critical in developing countries where drug quality assurance and regulatory systems for drug manufacturing, importation, distribution and sales are weak. A sustained...

Raman hyperspectral imaging is an increasingly used tool in the pharmaceutical field because it allows for the investigation of many characteristics on a solid sample. This paper delves into Raman spectroscopy and imaging, including spectral and spatial information, and presents some applications of Raman hyperspectral imaging in the pharmaceutical...

La spectroscopie proche infrarouge est une méthode d’analyse en plein développement. Force est de constater qu’elle est de plus en plus utilisée dans le secteur pharmaceutique pour le contrôle de qualité des produits. En effet, la spectroscopie proche infrarouge permet l’analyse rapide, non destructive, polyvalente des échantillons et ne nécessite...

Les médicaments de la dysfonction érectile constituent une des classes de médicaments les plus contrefaites dans les pays industrialisés. Pour lutter contre ce fléau, différentes approches analytiques sont à la disposition des laboratoires de contrôle. Cet article passe en revue les principales approches utilisées et conclut par la présentation d'u...

Vibrational spectroscopy (MIR, NIR and Raman) based hyperspectral imaging is one of the most powerful tools to analyze pharmaceutical preparation. Indeed, it combines the advantages of vibrational spectroscopy to imaging techniques and allows therefore the visualization of distribution of compounds or crystallization processes. However, these techn...

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...

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 a...

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 subst...

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...

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 conc...

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...

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 such as infrared spectroscopy and Raman spectroscopy have always been the first methods of choice to detect counterfeits and illegal preparations,...

Chromatographic fingerprints recorded for a set of genuine and counterfeit samples of Viagra(®) and Cialis(®) were evaluated for their use in the detection and classification of counterfeit samples of these groups of medicines. Therefore several exploratory chemometric techniques were applied to reveal structures in the data sets as well as differe...

A fast headspace GC-MS method was developed and validated for the detection and quantification of residual solvents of all three ICH-classes in counterfeit tablets and capsules. The method was validated for 10 solvents, selected based on an initial screening of counterfeit medicinal products. The considered solvents were ethanol, 2-propanol, aceton...

Most of the counterfeit medicines are manufactured in non good manufacturing practices (GMP) conditions by uncontrolled or street laboratories. Their chemical composition and purity of raw materials may, therefore, change in the course of time. The public health problem of counterfeit drugs is mostly due to this qualitative and quantitative variabi...

Classification trees built with the Classification And Regression Tree algorithm were evaluated for modelling infrared spectroscopic data in order to discriminate between genuine and counterfeit drug samples and to classify counterfeit samples in different classes following the RIVM classification system. Models were built for two data sets consist...