References of "Hubert, Philippe"
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See detailContinuous Production of Itraconazole-based Solid Dispersions by Hot Melt Extrusion: Preformulation, Optimization and Design Space Determination.
Thiry, Justine ULg; Lebrun, Pierre; Vinassa, Chloé et al

in International Journal of Pharmaceutics (in press)

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See detailQuantitative determination of salbutamol sulfate impurities using achiral supercritical fluid chromatography
Dispas, Amandine ULg; Desfontaine, Vincent; Andri, Bertyl ULg et al

in Journal of Pharmaceutical & Biomedical Analysis (2017), 134

In the last years, supercritical fluid chromatography has largely been acknowledged as a singular and performing technique in the field of separation sciences. Recent studies highlighted the interest of ... [more ▼]

In the last years, supercritical fluid chromatography has largely been acknowledged as a singular and performing technique in the field of separation sciences. Recent studies highlighted the interest of SFC for the quality control of pharmaceuticals, especially in the case of the determination of the active pharmaceutical ingredient (API).Nevertheless, quality control requires also the determination of impurities. The objectives of the present work were to i) demonstrate the interest of SFC as a reference technique for the determination of impurities in salbutamol sulfate API and ii) to propose an alternative to a reference HPLC method from the European Pharmacopeia (EP) involving ionpairing reagent. Firstly, a screening was carried out to select the most adequate and selective stationary phase. Secondly, in the context of robust optimization strategy, the method was developed using design space methodology. The separation of salbutamol sulfate and related impurities was achieved in 7 minutes, which is seven times faster than the LC-UV method proposed by European Pharmacopeia (total run time of 50 minutes). Finally, full validation using accuracy profile approach was successfully achieved for the determination of impurities B, D, F and G in salbutamol sulfate raw material. The validated dosing range covered 50 to 150 % of the targeted concentration (corresponding to 0.3 % concentration level), LODs close to 0.5 μg/mL were estimated. The SFC method proposed in this study could be presented as a suitable fast alternative to EP LC method for the quantitative determination of salbutamol impurities. [less ▲]

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See detailASSURANCE QUALITE et RECHERCHE …
Hubert, Philippe ULg

Scientific conference (2016, December 01)

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See detailMonitoring of anatabine release by methyl jasmonate elicited BY-2 cells using surface-enhanced Raman scattering
De Bleye, Charlotte ULg; Dumont, Elodie ULg; Dispas, Amandine ULg et al

in Talanta (2016), 160

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 ... [more ▼]

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 anatabine in a complex matrix comprising the culture medium and BY-2 cells. The second step was the calibration. This one was successfully performed directly in the culture medium in order to take into account the matrix effect, by spiking the medium with different concentrations of anatabine, leading to solutions ranging from 250 to 5000 µg L-1. A univariate analysis was performed, the intensity of a band situated at 1028 cm-1, related to anatabine, was plotted against the anatabine concentration. A linear relationship was observed with a R2 of 0.9951. During the monitoring study, after the MeJa elicitation, samples were collected from the culture medium containing BY-2 cells at 0, 24h, 48h, 72h and 96h and were analyzed using SERS. Finally, the amount of anatabine released in the culture medium was determined using the response function, reaching a plateau after 72h of 82 µg of anatabine released / g of fresh weight (FW) MeJa elicited BY-2 cells. [less ▲]

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See detailA simple calibration approach based on film-casting for confocal Raman microscopy to support the development of a Hot-Melt Extrusion process
Netchacovitch, Lauranne ULg; Thiry, Justine ULg; De Bleye, Charlotte ULg et al

in Talanta (2016), 154

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 ... [more ▼]

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 circumvent this issue, the paper presents a simple approach based on the film-casting technique used as a calibration tool in the framework of hot-melt extrusion process. Confocal Raman microscopic method was successfully validated for the determination of itraconazole content in film-casting samples. Then, hot-melt extrusion was carried out to produce real samples in order to confront the results obtained with confocal Raman microscopy and Ultra High Performance Liquid Chromatography (UHPLC). The agreement between both methods was demonstrated using a comparison study based on the Bland and Altman’s plot. [less ▲]

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See detailMOISTURE CONTENT DETERMINATION OF FREEZE-DRIED PRODUCTS BY NEAR-INFRARED SPECTROSCOPY: A CASE STUDY FOR UNIVERSAL REGRESSION MODEL
Clavaud, Matthieu ULg; Roggo, Yves; Degardin, Klara et al

Poster (2016, June 06)

Karl Fischer titration is the reference method for moisture content determination in the pharmaceutical industry. Near-infrared spectroscopy is considered the most suitable alternative technique. Indeed ... [more ▼]

Karl Fischer titration is the reference method for moisture content determination in the pharmaceutical industry. Near-infrared spectroscopy is considered the most suitable alternative technique. Indeed, NIRS is a safe and fast method which does not require sample preparation. Nevertheless, the development and validation phases are time-consuming. In addition, the NIRS methods presented so far were mostly product specific. The main objective of this study is to highlight that an universal calibration model can be validated for several freeze-dried products in order to speed up the validation time. This objective was led in two steps. A universal model was first evaluated. A calibration set and a validation set were built up with three freeze-dried products. An antibody drug conjugate, a large molecule and a small molecule all packed in sealed vials were used to introduce more variability. Regression methods were then compared in order to optimize the prediction values. [less ▲]

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See detailScreening study of SFC critical method parameters for the determination of pharmaceutical compounds
Dispas, Amandine ULg; Lebrun, Pierre ULg; Sacre, Pierre-Yves ULg et al

in Journal of Pharmaceutical & Biomedical Analysis (2016), 125

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 ... [more ▼]

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 work was to evaluate the impact of different critical method parameters (CMPs), i.e. stationary phase, mobile phase composition and injection solvent nature. The experiments were performed considering two groups of antimalarial molecules: one group with neutral/apolar compounds and the other one with salt form of polar compounds. In this context, another objective was to propose a suitable sample solvent for quantitative analysis. The interest of new generation stationary phase to obtain good peak shape and the interest to tune the mobile phase composition were demonstrated. During this study, design of experiments and desirability function approach enabled to highlight optimal chromatographic conditions in order to maximise peak capacity and to get acceptable value of symmetry factor. Regarding sample injection solvent composition, some counterintuitive results were observed: solvents closer to the mobile phase polarity (i.e heptane or 2-propanol/heptane mixture) did not provide best results in terms of peak symmetry. In addition, acetonitrile and short aliphatic alcohols offered an interesting alternative as injection solvent: toxicity of solvents used is clearly reduced and better quantitative performances could be expected while keeping high peak capacity and symmetric sharp peaks. Finally, the quantitative performances were evaluated by the method validation for the quantitative determination of quinine sulfate in a pharmaceutical formulation. These better understandings on critical method parameters led SFC to be an even more promising technique in the field of the analysis of pharmaceutical compounds. [less ▲]

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See detailMédicaments usage de faux
Sacre, Pierre-Yves ULg; Ziemons, Eric ULg; Hubert, Philippe ULg et al

Article for general public (2016)

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See detailImplementing principles of Quality by Design (QbD) in validation context
Hubert, Cédric ULg; Lebrun, Pierre ULg; Rozet, Eric et al

Conference (2016, May 10)

Analytical method performances have to be specified by the analyst trough the definition of the “Analytical Target Profile (ATP)”, as proposed by the regulatory bodies. In the specific context of the ... [more ▼]

Analytical method performances have to be specified by the analyst trough the definition of the “Analytical Target Profile (ATP)”, as proposed by the regulatory bodies. In the specific context of the pharmaceutical industry, regulatory authorities have recently imposed the assessment and management of risk throughout the entire product lifecycle. This includes the analytical procedure and consequently its own lifecycle. The development step of an analytical method is still largely addressed using a “Changing One Separate Factor a Time (COST)” approach (also known as the “Quality-by-Testing (QbT)” approach). This strategy can lead to a suitable method for assessing the risk of routine use, even where the experimental domain is not examined. However, in order to consider an experimental domain rather than a set of specific experimental conditions during the development phase, a multivariate approach must be considered: the “Quality-by-Design (QbD)” strategy. This strategy allows the definition of a “Design Space (DS)” by means of design of experiments (DoE). This DS, computed considering critical method parameters, allows the analyst to focus on the main objective of an analytical method: obtaining reliable results using a robust method. In the course of a specific case study, the benefits of the QbD strategy in terms of managing the qualitative part of the analytical process were highlighted. Working in the context of analytical procedure, the validation step is a major part of the analytical method lifecycle. Indeed, the objective of analytical method validation is to demonstrate that this method is suited for quantifying the target analytes with an established and suitable level of accuracy, as defined by the “ATP”. This is sometimes called the “fit-for-future-purpose” concept. The decision regarding the validity of a method based on prediction can be achieved by using the “β-expectation tolerance interval” (accuracy profile). The capability of this approach to manage the quantitative part of the analytical procedure is nowadays largely illustrated in scientific literatures. Considering the assessment and management of risk throughout the analytical lifecycle, a global strategy allowing the unification of the development and validation phases in a single step was considered. With this innovative approach, a strategy allowing the management of global analytical risk (i.e., for both qualitative and quantitative part of the analytical method) was proposed. Indeed, the developed strategy allows validating an entire experimental domain by means of the accuracy profile rather than a single set of specific experimental conditions. With this strategy, the DS is no longer simply the place where qualitative performances are obtained, but also the space where quantitative performances of the analytical procedure are assessed and managed. [less ▲]

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