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See detail‘Quality by Design’ approach for the analysis of impurities in pharmaceutical drug products and drug substances
Dispas, Amandine ULiege; Avohou, Tonakpon Hermane ULiege; Lebrun, Pierre ULiege et al

in Trends in Analytical Chemistry (in press)

The pharmaceutical industry is highly regulated by quality policies. The concept of risk management is strongly integrated into the quality assurance system to ensure pharmaceuticals’ quality and ... [more ▼]

The pharmaceutical industry is highly regulated by quality policies. The concept of risk management is strongly integrated into the quality assurance system to ensure pharmaceuticals’ quality and patients’ safety. In the context of quality control, the detection of impurities in raw materials and finished products is a major concern. It can be challenging for analytical scientists to meet specificity/selectivity and sensitivity requirements. Obviously, separation techniques are widely used for the detection of impurities but the method development required to achieve Analytical Target Profile (ATP) concerns is often challenging. Therefore, to ensure pragmatic and systematic methods development and simultaneously manage the risk associated with analytical methods, the principles of Quality by Design (QbD) should be applied. This paper provides an overview of QbD principles and statistical strategies (mainly DoE-DS approach) which can be applied to impurity detection methods, as well as a review of the literature where QbD has been applied to these types of analytical methods. [less ▲]

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See detailCritical review of surface-enhanced Raman spectroscopy applications in the pharmaceutical field
Cailletaud, Johan ULiege; De Bleye, Charlotte ULiege; Dumont, Elodie ULiege et al

in Journal of Pharmaceutical & Biomedical Analysis (2018), 147

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 ▼]

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 analytical performance of SERS is limited due to the difficulty to implement a quantitative methodology correctly validated. Nevertheless, some studies reported the development of SERS quantitative methods especially in pharmaceutical approaches. In this context, this review presents the main concepts of the SERS technique. The different steps that need to be applied to develop a SERS quantitative method are also deeply described. The last part of the present manuscript gives a critical overview of the different SERS pharmaceutical applications that were developed for a non-exhaustive list of pharmaceutical compounds with the aim to highlights the validation criteria for each application. [less ▲]

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See detailRaman Chemical Imaging in Kidney Stone Analysis
Castiglione, Vincent ULiege; Sacre, Pierre-Yves ULiege; CAVALIER, Etienne ULiege et al

Poster (2017, November 02)

Background: The structure of kidney stones might provide clinical useful information in addition to the stone composition. The Raman chemical imaging (RCI) is a new technology used for the production of ... [more ▼]

Background: The structure of kidney stones might provide clinical useful information in addition to the stone composition. The Raman chemical imaging (RCI) is a new technology used for the production of two-dimensions maps of the constituents' distribution in samples. We aimed at determining the use of RCI in urinary stone analysis. Methods: Twelve calculi were analyzed by RCI using a confocal Raman microspectrophotometer. They were selected according to their heterogeneous composition and morphology. Prior to the analysis, samples were sliced and milled in order to detect the nucleus of the stones and having a smooth surface. RCI was performed on the whole section of stones. Once acquired, the data were baseline corrected and analyzed by MCR-ALS. Results were then compared to the spectra obtained by Fourier Transform Infrared spectroscopy, the gold standard method for the determination of urolithiasis composition. Results: RCI succeeded in identifying all the chemical components contained in each sample, including monohydrate and dihydrate calcium oxalate, anhydrous and dihydrate uric acid, apatite, struvite, brushite, whitlockite and ammonium urate. However, proteins couldn't be detected because of the huge autofluorescence background and the small concentration of these poor Raman scatterers. Carbapatite and calcium oxalate were correctly detected even when they represented less than 5 percent of the whole stones, allowing the detection of very small structures like Randall's plaques. Moreover, RCI provided the distribution of components within the stones. The nuclei were accurately identified, as well as thin layers of other components. Conversion of dihydrate to monohydrate calcium oxalate was correctly observed in the center of one sample. Conclusion: RCI showed a good accuracy in comparison with infrared spectroscopy in identifying components of kidney stones. In addition, RCI is nondestructive enabling the storage of samples. This analysis was also useful in determining the organization of components within stones, which help locating constituents in low quantity, such as nuclei. However, this analysis is time-consuming, which makes it more suitable for research studies rather than routine analysis. [less ▲]

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See detailLes risques toxicologiques liés aux médicaments de qualité inférieure
Marini Djang'Eing'A, Roland ULiege; Kalenda Tshilombo, Nicodème ULiege; Ciza Hamuli, Patient ULiege et al

Conference (2017, October 19)

Objective: Poor quality medicines regrouping counterfeit/falsified, sub-standards and degraded are a scourge for developing countries (1). Their public health consequences are often observed for cases of ... [more ▼]

Objective: Poor quality medicines regrouping counterfeit/falsified, sub-standards and degraded are a scourge for developing countries (1). Their public health consequences are often observed for cases of low dosage of active ingredients and sometimes for the absence of these. On the basis of the observed facts as well as suspected reported cases, we were interested in deepening the information through laboratory tests. Methods: Liquid chromatography (LC), thin layer chromatography (TLC), nuclear magnetic resonance (NMR), mass spectrometry (MS), Raman imagery (Rim) and near infrared spectroscopy (NIR) were used as targeted analytical techniques in this study, associated with the principal component analysis (PCA), while the suspect samples were obtained via the public health authorities of the DR Congo, Benin and Rwanda after their seizure. Results: The observed cases are presented by therapeutic class, namely: - analgesics: (1) cases of tablets supposed to contain paracetamol and which have caused abnormal adverse effects in patients who have consumed it, namely sedative effects, polyuria and hypotension. Using LC and complementary surveys by people interview, we were able to demonstrate the presence of a benzodiazepine and at very high doses. (2) Cases of paracetamol syrup whose excipient (glycerol) was substituted by diethylene glycol and which had caused the death of a hundred babies. Using the NIR and the PCA, we were able to elucidate this substitution. - antimalarials: (case 1) cases of arthemether-lumefantrine tablets which had no therapeutic effect. By means of TLC and LC, the absence of these two active ingredients was clearly demonstrated, but the presence of starch was revealed by Rim. (Case 2) case of quinine tablets that had no expected pharmacological effect. The use of several combined techniques (TLC, LC-MS, NMR and Rim) made it possible to demonstrate the presence of a substance with an imidazole structure (antamoeba). - antibiotics: (1) amoxicillin powder which after reconstitution in hospital caused poisoning of the babies until death for some. The reconstitution of the suspension had revealed the misuse of hydrogen peroxide instead of distilled water. (2) Finally a large-scale study (80 samples of amoxicillin powder) showed that 8% of the samples were above the claimed dosage. Conclusion: The cases presented indicate that there are effectively poor quality medicines and that they are responsible of public health problems and in particular of toxicity. Appropriate measures should be taken to protect users. [less ▲]

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See detailThe quality of artemether-lumefantrine combination and characteristics of pharmacies in the periurban areas of kinshasa
Mavungu Landu, Don Jethro ULiege; Liégeois, Sophie; Manzambi Kuwekita, Joseph ULiege et al

Conference (2017, October 18)

QUALITÉ DE LA COMBINAISON THERAPEUTIQUE ARTEMETHER-LUMEFANTRINE ET CARACTÉRISTIQUES DES PHARMACIES EN TERRITOIRES PÉRIURBAINS DE KINSHASA Mavungu Landu DJ.1,2, Liégeois S., Manzambi Kuwekita J.3,4, Mbinze ... [more ▼]

QUALITÉ DE LA COMBINAISON THERAPEUTIQUE ARTEMETHER-LUMEFANTRINE ET CARACTÉRISTIQUES DES PHARMACIES EN TERRITOIRES PÉRIURBAINS DE KINSHASA Mavungu Landu DJ.1,2, Liégeois S., Manzambi Kuwekita J.3,4, Mbinze J.5, Mavungu Nsiona J.6,Hubert P.1, Michel B.2,7, Gretry L.8, Minga Kwete M.9, Reginster J-Y.3, Frédérich M.1, Marini Djang'Eing'A R.1 1 Département de Pharmacie, Université de Liège, Liège, Belgique; 2 Ecole Régionale Postuniversitaire d’Aménagement et de Gestion intégrés des Forêts et Territoires tropicaux, Kinshasa, RDC; 3 Département des Sciences de la Santé Publique, Université de Liège, Liège, Belgique; 4 Section de Santé Communautaire, Institut Supérieur des Techniques Médicales de Kinshasa, Kinshasa, RDC; 5 Département de Galénique et d’Analyse des Médicaments, Université de Kinshasa, Kinshasa, RDC; 6 Division Provinciale de la Santé, Kinshasa, RDC; 7 Faculté Universitaire des Sciences Agronomiques de Gembloux, Université de Liège, Gembloux, Belgique; 8 Plateforme Afrique Centrale, PACODEL, Kinshasa, RDC; 9 Secure drug, Kinshasa, RDC. Introduction: Le paludisme causé par le Plasmodium falciparum demeure un problème majeur de santé publique. Le traitement avec des antipaludiques de bonne qualité est une composante importante dans le contrôle de cette maladie. Cependant en Afrique centrale, plus de 25% des médicaments serait contrefaits ou de qualité inférieure, situation qui serait encore plus dramatique dans les territoires périurbains. Objectif: Afin de permettre une sensibilisation des populations vivant dans ces milieux, une étude a été menée dans le but d’évaluer l’existant au niveau sanitaire pharmaceutique. Méthodes: Dans le contexte ci-mentionné, une étude préliminaire et prospective a été menée dans la zone de santé de Mont Ngafula 1 située dans les territoires périurbains de la Ville de Kinshasa durant la période allant du 22 février au 10 décembre 2016. Trente échantillons de poudre pour suspension d’artéméther et de luméfantrine ont été collectés. L’analyse de la qualité de ces médicaments a été réalisée au moyen de méthodes séparatives génériques utilisant la technique de chromatographie liquide à haute performance couplé à un détecteur à barrettes de diodes. Une caractérisation a été également effectuée dans 127 établissements pharmaceutiques sur base des normes édictées par le Ministère de la Santé Publique congolais. Résultats: Le résultat des analyses des échantillons d’antimalariques (ou antipaludéens) montre qu’une poudre pour suspension d’artéméther et de luméfantrine sur trois (33,3%) ne contenait pas la concentration prévue en artéméther et/ou en luméfantrine. Par ailleurs, le résultat des observations évoque qu’aucun établissement pharmaceutique ne respectait l’ensemble des normes du Ministère de la Santé Publique. Conclusion: Cette étude nous apprend qu’en territoires périurbains de Kinshasa, un échantillon sur trois (33,3%) de la combinaison Artéméther-Luméfantrine est non conforme, les suspensions sont sous-dosées. Quant aux pharmacies existantes, aucune d’entre elles ne respecte l’ensemble des normes minimales édictées par le Ministère de la Santé Publique de la RDC. [less ▲]

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See detailDrepakis : Contribution to the management of Sickle cell disease in the city of Kisangani (D.R. Congo)
Marini Djang'Eing'A, Roland ULiege; Batina Agasa, Salomon; Gulbis, Béatrice et al

Conference (2017, October 06)

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See detailInvestigation of content of Panda oleosa (Pierre), a plant used in Kisangani areas for its antihyperglycemic activity
Katemo Muhoya, Frédéric; Kadima Ntokamunda, Justin; Njakarinala Ranarivelo et al

Conference (2017, October 05)

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See detailPoor quality medicines in Africa: how to combat this real scourge
Marini Djang'Eing'A, Roland ULiege; Sacre, Pierre-Yves ULiege; Ziemons, Eric ULiege et al

Conference (2017, October 04)

Poor (or low) quality medicines remain a crucial problem of public health around the world. They encompass falsified /counterfeit, substandard or degraded drugs. If proportion of 1% is estimated in ... [more ▼]

Poor (or low) quality medicines remain a crucial problem of public health around the world. They encompass falsified /counterfeit, substandard or degraded drugs. If proportion of 1% is estimated in developed countries, they are globally about 10 % of counterfeit drugs according to Food and Drug Administration, with 30% in low income countries and astonishing values (80 %) reported in some African countries. The consequences and dangers of such medicines are therapeutic failure, drug poisoning, microbial resistance or even death. For the pharmaceutical industries, there are loss of image, loss of financial income and employment. There is need to combat this scourge, but most of the time, means are very limited and even lacking. In this context, several means or tools are developed by the ULg Pharmacy Department including the simple ones including organoleptic tests, simple analytical tests such as analytical balance, pHmeter, thin layer chromatography (TLC), UV-visible spectrophotometry to the more complex including liquid chromatography (LC) coupled to UV-Vis detector, or to mass spectrometry, nuclear magnetic resonance, Raman imagery (RIM) and near infrared (NIR) spectroscopy associated with the principal component analysis (PCA). In this way, we have analyzed several suspected samples obtained via the public health authorities of the D.R. Congo, Benin and Rwanda after their seizure or through collaborations. The results are presented by therapeutic class, namely: analgesics: - by using LC and complementary information from victim patients, we were able to discover an abnormal presence of a benzodiazepine at very high doses in paracetamol tablets which was the cause of unusual adverse effects (sedative effects, polyuria and hypotension) in patients who have consumed it; - by using the NIR-PCA, we were able to elucidate the substitution of an excipient (glycerol) by diethylene glycol in paracetamol syrup which caused the death of a hundred babies. antimalarials: - we faced cases of arthemether-lumefantrine tablets which had no therapeutic effect. By means of TLC and LC, the absence of these two active ingredients was clearly demonstrated, but the presence of starch was revealed by RIM; - another case of quinine tablets that had no expected pharmacological effect was faced. The use of several combined techniques (TLC, LC-MS, NMR and RIM) allowed to detect the presence of a substance with an imidazole structure (antamoeba). antibiotics: - the case of amoxicillin powder which after reconstitution in hospital caused poisoning of the babies until death for some was investigated. The reconstitution of the suspension in the laboratory had revealed the misuse of hydrogen peroxide instead of distilled water; - we participated to a large-scale study (80 samples of amoxicillin powder) that showed 8% of overdose. The cases presented indicate that there are effectively poor quality medicines and there is need to sustain strong collaborations while reinforcing appropriate measures to protect users. [less ▲]

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See detailTowards a covering aerospray method for quantitative analyses of pharmaceutical tablets using surface-enhanced Raman chemical imaging (SER-CI)
Cailletaud, Johan ULiege; De Bleye, Charlotte ULiege; Dumont, Elodie ULiege et al

Conference (2017, September 22)

In recent years, the use of SERS-CI in pharmaceutical sciences has increased in order to study the distribution of low-dose compounds in solid dosage forms [1]. This technique allows to improve the ... [more ▼]

In recent years, the use of SERS-CI in pharmaceutical sciences has increased in order to study the distribution of low-dose compounds in solid dosage forms [1]. This technique allows to improve the sensitivity of conventional Raman microscopy and to reduce significantly the image acquisition time by exalting the signal information. However, the applications of SERS-CI in the pharmaceutical field remain limited, especially due to the difficulty of obtaining a homogeneous deposit of metallic nanoparticles on the sample surface. Generally, the covering method used on the tablet is a drop casting deposition due to its simplicity and rapidity of implementation. Despite the colloidal solution deposit is not fully controlled. The inhomogeneous covering is the result of the “coffee-ring” effect that concentrates the nanoparticles at the edges of the droplet [2]. This implies remarkable variations of the SERS analyte signal’s intensity at different places. For a more reproducible and homogeneous coating, an aerospray method using a homemade apparatus was developed (Figure 1). The device is composed with a pair of coaxial tubes, the colloidal solution is pulled through the inner tube from a syringe pump and the outer tube is connected to a source of high pressure gas. Nitrogen, used as a nebulizing gas, creates a flow of small droplets of nanoparticles that are nearly dry when they hit the sample surface. The aerospray device is easy to implement and the entire surface of the tablet is covered by the SERS substrate in a homogeneous way. By using this covering method, the potential of SERS-CI is improved and making it a suitable technique for quantitative analyses of low drug concentrations or impurities in pharmaceutical tablets. [less ▲]

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See detailTowards the development of a dual mode fluorescence/SERS dopamine aptasensor
Dumont, Elodie ULiege; De Bleye, Charlotte ULiege; Cailletaud, Johan ULiege et al

Poster (2017, September 21)

This work was dedicated to the development of a dual mode fluorescence and surface-enhanced Raman scattering (SERS) dopamine aptasensor. The preparation of the aptasensor was first optimised. Thereafter ... [more ▼]

This work was dedicated to the development of a dual mode fluorescence and surface-enhanced Raman scattering (SERS) dopamine aptasensor. The preparation of the aptasensor was first optimised. Thereafter, calibration curves were realised by means of fluorescence quenching and SERS. Finally, the specificity of both methods was tested. [less ▲]

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See detailSimple LC Isocratic Methods Development, Validation, and Application in the Analysis of Poor Quality Antimalarial Medicines
Habyalimana, Védaste ULiege; Mbinze Kindenge, Jéremie; Yemoa Loconon, Achille et al

in American Journal of Analytical Chemistry (2017), 8

Liquid chromatographic methods in isocratic mode for the analysis of poor quality medicines are privileged due to their simplicity and facility in methods development. They are generally fast; do not need ... [more ▼]

Liquid chromatographic methods in isocratic mode for the analysis of poor quality medicines are privileged due to their simplicity and facility in methods development. They are generally fast; do not need to be re-equilibrated between sample injections; have larger flexibility with acceptable changes on different column dimensions; and are applicable to LC systems equipped with simple or high developed pumps. In this study, we focused on developing simple isocratic methods using classical mobile phase composed by methanol and ammonium formate buffer for the analysis of most common antimalarial medicines marketed in malaria endemic countries and susceptible of being counterfeit/falsified, substandard and degraded. The selected medicines were quinine and related cinchona alkaloids in tablets and injectable forms; artemether/ lumefantrine tablets; and artemisinin compounds (arteether, artemether, and artesunate) in injectable forms. The current methods were developed thanks to simple methodological approach consisting in sequential isocratic runs through adjustment or adaptation of existing methods to obtain optimal analytical conditions without complex design of experiments that might be long and costly. Then, the new methods presented shorter analysis time; allowed increase of sample analysis throughput; and obviously consumed little mobile phase solvents on classical analytical columns: 50 - 250 mm of length (L), 4.6 mm of internal diameter (I.D.), and 3.5 - 5.0 μm of particle size (dp). [less ▲]

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See detailDevelopment of SERS nanosensors for the detection of small bioactive molecules by cellular analysis in complex matrices: Application to dopamine
Dumont, Elodie ULiege; De Bleye, Charlotte ULiege; Cailletaud, Johan ULiege et al

Conference (2017, September 13)

This communication reports the different steps undertaken in order to develop a new Surface-Enhanced Raman Scattering (SERS) nanosensor for the quantification of dopamine in the culture medium of PC-12 ... [more ▼]

This communication reports the different steps undertaken in order to develop a new Surface-Enhanced Raman Scattering (SERS) nanosensor for the quantification of dopamine in the culture medium of PC-12 cells. First, the synthesis of the SERS substrate, gold nanoparticles, and its characterization. Then the development of the method with the help of a design of experiments and the demonstration of the specificity of the method over other structurally related catecholamines. And finally, the implementation of the method on the culture medium of PC-12 cells, on an HEPES buffer having served to wash the cells and on the PC-12 cells. [less ▲]

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See detailPreliminary Phytochemical Content and Antidiabetic Potential Investigations of Panda oleosa (Pierre) Used in Kisangani Areas
Katemo Muhoya, Frédéric; Kadima Ntokamunda, Justin; Njakarinala Ranarivelo et al

in American Journal of Analytical Chemistry (2017), 8

Panda oleosa Pierre (POP), a tropical plant tree, has been used in traditional medicine in Kisangani city and around to treat various diseases including diabètes and HIV/AIDs. This study aims to evaluate ... [more ▼]

Panda oleosa Pierre (POP), a tropical plant tree, has been used in traditional medicine in Kisangani city and around to treat various diseases including diabètes and HIV/AIDs. This study aims to evaluate the chemical composition of POP extracts while setting up chromatographic fingerprints for their quality control, and the anti-hyperglycemic potential of trunk bark aqueous extracts of POP. Common chemical reactions were used for identification of main secondary metabolic groups. Thin layer chromatography was used to set up several chromatographic fingerprints of water and alcoholic extracts while evaluating chemical composition. Oral glucose tolerance test served to induce hyperglycemia in a rabbit model. The extracts were given as 25 mg/kg, 50 mg/kg, and 100 mg/kg body weight, 30 minutes before loading animals with glucose 4 g/kg. Blood samples were collected at various times: just before extracts (T-30), before (T0) and after glucose load (T30, T60, T120, and T180). Blood glucose levels were measured with One Touch Glucometer. The identification tests revealed the presence of saponins (3.58%), tannins (5%); alkaloids, quinones, flavonoids, and terpenes sterols could not be formerly detected by the reagents used. Interesting chromatographic spots were observed whose behaviors are of catechic tannin proanthocyanes. The extract significantly reduced glucose levels in dose dependent manner as compared to control and glibenclamide reference groups. The average of mean percentage of reduction in glucose level at T120 with the extract 100 mg/kg was close to that of glibenclamide 0.25 mg/kg (49% and 40.2%). These findings back the traditional use of the plant to treat diabetic patients and constitute a foundation for an extensive study to find a new antidiabetic phythomedicine. [less ▲]

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See detailIs supercritical fluid chromatography hyphenated to massspectrometry suitable for the quality control of vitamin D3 oilyformulations?
Andri, Bertyl ULiege; Dispas, Amandine ULiege; Klinkenberg, Régis et al

in Journal of Chromatography. A (2017), 1515

Nowadays, many efforts are devoted to improve analytical methods regarding efficiency, analysis timeand greenness. In this context, Supercritical Fluid Chromatography (SFC) is often regarded as a ... [more ▼]

Nowadays, many efforts are devoted to improve analytical methods regarding efficiency, analysis timeand greenness. In this context, Supercritical Fluid Chromatography (SFC) is often regarded as a goodalternative over Normal Phase Liquid Chromatography (NPLC). Indeed, modern SFC separations arefast, efficient with suitable quantitative performances. Moreover, the hyphenation of SFC to mass spec-trometry (MS) provides additional gains in specificity and sensitivity. The present work aims at thedetermination of vitamin D3 by SFC-MS for routine Quality Control (QC) of medicines specifically. Basedon the chromatographic parameters previously defined in SFC-UV by Design of Experiments (DoE) andDesign Space methodology, the method was adapted to work under isopycnic conditions ensuring a base-line separation of the compounds. Afterwards, the response provided by the MS detector was optimizedby means of DoE methodology associated to desirability functions. Using these optimal MS parameters,quantitative performances of the SFC-MS method were challenged by means of total error approachmethod validation. The resulting accuracy profile demonstrated the full validity of the SFC-MS method. It was indeed possible to meet the specification established by the European Medicines Agency (EMA) (i.e. 95.0 − 105.0% of the API content) for a dosing range corresponding to at least 70.0-130.0% of theAPI content. These results highlight the possibility to use SFC-MS for the QC of medicine and obviouslysupport the switch to greener analytical methods. [less ▲]

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See detailGlobal regression model for moisture content determination using near-infrared spectroscopy
Clavaud, Matthieu ULiege; Roggo, Yves; Degardin, Klara et al

in European Journal of Pharmaceutics and Biopharmaceutics (2017), 119

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 ... [more ▼]

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 0.05% to 4.96%. Linear and non-linear regression models using Partial Least Square (PLS), Decision Tree (DT), Bayesian Ridge Regression (Bayes-RR), K-Nearest Neighbors (KNN), and Support Vector Regression (SVR) algorithms were created and evaluated. Among them, the SVR model was retained for a global application. The Standard Error of Calibration (SEC) and the Standard Error of Prediction (SEP) were respectively 0.12% and 0.15%. This model was then evaluated in terms of total error and risk-based assessment, linearity, and accuracy. It was observed that MC can be fastly and simultaneously determined in freeze-dried pharmaceutical products thanks to a global NIR model created with different medicines. This innovative approach allows to speed up the validation time and the in-lab release analyses. [less ▲]

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See detailImpact of formulation and process parameters on near-infrared spectra: Application for water determination in biopharmaceuticals
Clavaud, Matthieu ULiege; Roggo, Yves; Allmendinger, Andrea et al

Poster (2017, June 11)

Traditionally, the water content of freeze-dried biopharmaceuticals is determined by time-consuming methods such as Karl Fischer titration. As a fast and non-destructive method, many studies demonstrated ... [more ▼]

Traditionally, the water content of freeze-dried biopharmaceuticals is determined by time-consuming methods such as Karl Fischer titration. As a fast and non-destructive method, many studies demonstrated the efficiency of Near-Infrared (NIR) spectroscopy for that purpose [1]. In this study, NIR was applied to different freeze-dried monoclonal antibody. The aim was to evaluate the robustness of a NIR model depending on formulation composition and process parameters of the lyophilization parameters, and the benefits of NIR when developing a freeze-drying cycle for a new pharmaceutical product. A full Design of experiments (DoE) was established in order to produce materials with various formulations and various process parameters. As a first step, a calibration model was created and validated. The model creation was based on 4 target lyophilized cycles which were manufactured to obtain samples with different water content concentration. Then, 20 lyophilized cycles were produced according to the DoE. Two levels of protein and sucrose concentration, and two levels of pressure / primary drying temperature and process time were investigated. Furthermore, several samples of each experiment stored at different temperature and relative humidity conditions were evaluated. Chemometrics using Principal Component Analysis (PCA) and Partial Least Squares (PLS) were used to evaluate the process variations and to determine the water content, respectively. NIR is capable to differentiate between different lyophilization process conditions, based on chemometrics. Robust calibration NIR model for water determination was generated against KF independent on lyophilization process parameters and formulation composition. NIR is suitable and robust method for drug product development of freeze-dried formulation. [less ▲]

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See detailRaman Hyperspectral Imaging: An essential tool in the pharmaceutical field
Sacre, Pierre-Yves ULiege; Netchacovitch, Lauranne ULiege; Dumont, Elodie ULiege et al

E-print/Working paper (2017)

Resulting from the combination of Raman spectroscopy and optical microscopy, Raman hyperspectral imaging has proven to be an indispensable tool in the pharmaceutical field. This article will broach a ... [more ▼]

Resulting from the combination of Raman spectroscopy and optical microscopy, Raman hyperspectral imaging has proven to be an indispensable tool in the pharmaceutical field. This article will broach a number of Raman hyperspectral imaging applications that were developed in our laboratory, in order to demonstrate the significance of the technique. [less ▲]

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