References of "Thiry, Justine"
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See detailBioavailability enhancement of itraconazole-based solid dispersions produced by hot melt extrusion in the framework of the Three Rs rule
Thiry, Justine ULg; Kok, Miranda ULg; Collard, Laurence ULg et al

in European Journal of Pharmaceutical Sciences (2017), 99

Solid dispersion formulations made of itraconazole (ITZ) and Soluplus® (polyethylene glycol, polyvinyl acetate and polyvinylcaprolactame-based graft copolymer abbreviated SOL) were produced using hot melt ... [more ▼]

Solid dispersion formulations made of itraconazole (ITZ) and Soluplus® (polyethylene glycol, polyvinyl acetate and polyvinylcaprolactame-based graft copolymer abbreviated SOL) were produced using hot melt extrusion. Since ITZ possesses a water solubility of less than 1 ng/mL, the aim of this work was to enhance the aqueous solubility of ITZ, and thereby improve its bioavailability. The three formulations consisted of a simple SOL/ITZ amorphous solid dispersion (ASD), an optimized SOL/ITZ/AcDiSol® (super-disintegrant) ASD and an equimolar inclusion complex of ITZ in hydroxypropyl-β-cyclodextrin (substitution degree = 0.63, CD) with SOL. The three formulations were compared in vitro and in vivo to the marketed product Sporanox®. The in vitro enhancement of dissolution rate was evaluated using a biphasic dissolution test. In vitro dissolution results showed that all three formulations had a higher percentage of ITZ released than Sporanox® with the following ranking: SOL/ITZ/CD > SOL/ITZ/AcDiSol® > SOL/ITZ > Sporanox®. The bioavailability of these four formulations was evaluated in rats. The bioanalytical method was optimized so that only 10 μL of blood was withdrawn from the rats using specific volumetric absorptive microsampling devices. This enabled to keep the same rats during the whole study, which was in accordance with the Three Rs rules (reduction, refinement and replacement). Furthermore, this technique allowed the suppression of inter-individual variability. Higher Cmax and AUC were obtained after the administration of all three formulations compared to the levels after the use of Sporanox® as follows: SOL/ITZ/AcDiSol® > SOL/ITZ/CD > SOL/ITZ > Sporanox®. The inversion in the ranking between SOL/ITZ/CD and SOL/ITZ/AcDiSol® made impossible the establishment of an in vitro–vivo correlation. Indeed, very different release rates were obtained in vitro and in vivo for the two optimized formulations. These results suggest that ITZ would be protected inside the core of the SOL micelles even during the absorption step at the intestine, while some agents present in the intestinal fluids could displace ITZ from the hydrophobic cavity of CD by competition. [less ▲]

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See detailHot-Melt Extrusion as a Continuous Manufacturing Process to Form Ternary Cyclodextrin Inclusion Complexes
Thiry, Justine ULg; Krier, Fabrice; Ratwatte, Shenelka et al

in European Journal of Pharmaceutical Sciences (2017), 96

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See detailDevelopment of an analytical method for crystalline content determination in amorphous solid dispersions produced by Hot-Melt Extrusion using transmission Raman spectroscopy: A feasibility study.
Netchacovitch, Lauranne ULg; Dumont, Elodie ULg; Cailletaud, Johan ULg et al

in International Journal of Pharmaceutics (2017), 530(1-2), 249-255

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 ... [more ▼]

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 Biopharmaceutical Classification System class II drugs. One way to produce amorphous solid dispersions is the Hot-Melt Extrusion (HME) process. This study reported the development and the comparison of the analytical performances of two techniques, based on backscattering and transmission Raman spectroscopy, determining the crystalline remaining content in amorphous solid dispersions produced by HME. Principal Component Analysis (PCA) and Partial Least Squares (PLS) regression were performed on preprocessed data and tended towards the same conclusions: for the backscattering Raman results, the use of the DuoScan™ mode improved the PCA and PLS results, due to a larger analyzed sampling volume. For the transmission Raman results, the determination of low crystalline percentages was possible and the best regression model was obtained using this technique. Indeed, the latter acquired spectra through the whole sample volume, in contrast with the previous surface analyses performed using the backscattering mode. This study consequently highlighted the importance of the analyzed sampling volume. [less ▲]

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See detailGlobal approach for the validation of an in-line Raman spectroscopic method to determine the API content in real-time during a hot-melt extrusion process
Netchacovitch, Lauranne ULg; Thiry, Justine ULg; De Bleye, Charlotte ULg et al

in Talanta (2017)

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 ... [more ▼]

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 Ingredient (API) content in real-time. The method was validated based on a univariate and a multivariate approach and the analytical performances of the obtained models were compared. Moreover, on one hand, in-line data were correlated with the real API concentration present in the sample quantified by a previously validated off-line confocal Raman microspectroscopic method. On the other hand, in-line data were also treated in function of the concentration based on the weighing of the components in the prepared mixture. The importance of developing quantitative methods based on the use of a reference method was thus highlighted. The method was validated according to the total error approach fixing the acceptance limits at ± 15% and the α risk at ± 5%. This method reaches the requirements of the European Pharmacopeia norms for the uniformity of content of single-dose preparations. The validation proves that future results will be in the acceptance limits with a previously defined probability. Finally, the in-line validated method was compared with the off-line one to demonstrate its ability to be used in routine analyses. [less ▲]

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See detailSampling only ten microliters of whole blood for the quantification of poorly soluble drugs: Itraconazole as case study
Thiry, Justine ULg; Evrard, Brigitte ULg; Nys, Gwenaël ULg et al

in Journal of Chromatography. A (2017), 1479

Nowadays in animal studies, it is important to comply with the so-called Three Rs rule by replacing or reducing the number of tested animals. Volumetric absorptive microsampling (VAMS) can be used to ... [more ▼]

Nowadays in animal studies, it is important to comply with the so-called Three Rs rule by replacing or reducing the number of tested animals. Volumetric absorptive microsampling (VAMS) can be used to collect small quantities (10 or 20 µL) of whole blood, thereby limiting the amount of animals needed. In this study, a quantitative method was developed and subsequently validated for the poorly soluble drug itraconazole (ITZ) using VAMS and ultra-high performance liquid chromatography (UHPLC) coupled to tandem mass spectrometry (MS). A proof of concept study showed that the optimized method is applicable to test the bioavailability of drug formulations containing ITZ. Using VAMS, smaller blood volumes can be taken per sampling point (10-20 µL instead of the conventional 0.2-0.5 mL) avoiding the sacrifice of animals. Moreover, the same rats can be used to compare different drug formulations which strengthens the validity of the results. In long-term bioavailability studies, it is necessary to guarantee the stability of the tested drugs supported on VAMS devices. In this study, we show that ITZ was only stable for 24 hours after collection with VAMS, but for at least two weeks by the storage of extracted samples at -80°C. [less ▲]

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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 (2016), 515(1-2), 114-124

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See detailHot-Melt Extrusion as a Continuous Manufacturing Process to Form Ternary Cyclodextrin Inclusion Complexes
Thiry, Justine ULg; Krier, Fabrice; Ratwatte, Shenelka et al

Poster (2016, November 16)

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See detailPolyphosphoester containing amphiphilic block copolymers as drug nanocarriers
Ergül, Zeynep ULg; Vanslambrouck, Stéphanie; Thiry, Justine ULg et al

Poster (2016, September 12)

The design of drug delivery systems often requires biodegradable and biocompatible materials that allow safe retention and controlled release of the drug. In this respect, supramolecularly self-assembled ... [more ▼]

The design of drug delivery systems often requires biodegradable and biocompatible materials that allow safe retention and controlled release of the drug. In this respect, supramolecularly self-assembled amphiphilic block copolymers into spherical micelles are appropriate carriers for poorly soluble drugs. In that framework, we have designed novel functional poly(ethylene oxide)-b-polyphosphoester amphiphilic block copolymers able to cross-linked under UV and degrade in response to a reduction of the pH from neutral conditions. Therefore, an unsaturated alkene side-chain was introduced on the cyclic phosphate monomer according to a one-step reaction followed by its organocatalyzed polymerization initiated by a poly(ethylene oxide) macroinitiator. After self-assembly into water, the micelles were cross-linked by UV irradiation. Then, these cross-linked micelles have been loaded by doxorubicin, i.e. a drug used in cancer therapy. We observed that the doxorubicin loading increased with the number of double bonds on the polyphosphate block of non-cross-linked micelles. This diblock amphiphilic copolymer bearing pendant unsaturations appears thus particularly promising candidate to build micellar drug delivery systems for intravenous injection. [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 ▲]

Detailed reference viewed: 105 (29 ULg)
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See detailModeling, sensitivity analysis and parameter identification of a twin screw extruder
Grimard, Jonathan; Dewasme, Laurent; Thiry, Justine ULg et al

Conference (2016, June)

Detailed reference viewed: 38 (3 ULg)
See detailPolyphosphoester containing amphiphilic block copolymers as drug nanocarriers
Yilmaz-Ergül, Zeynep ULg; Vanslambrouck, Stéphanie; Thiry, Justine ULg et al

Poster (2016, May 23)

The design of drug delivery systems (DDS) often requires biodegradable and biocompatible materials that allow safe retention and controlled release of the drug. In this respect, poly(ethylene oxide)-b ... [more ▼]

The design of drug delivery systems (DDS) often requires biodegradable and biocompatible materials that allow safe retention and controlled release of the drug. In this respect, poly(ethylene oxide)-b-polyphosphoester amphiphilic block copolymers are known to self-assemble into polymer micelles when placed in water are appropriate drug carriers. In this work, an unsaturated alkene side-chain was introduced on the cyclic phosphate monomer according to a one-step reaction followed by its organocatalyzed polymerization initiated by a poly(ethylene oxide) macroinitiator. After self-assembly into water, the micelles were cross-linked by UV irradiation. Then, these cross-linked micelles have been loaded by doxorubicin, which is a drug to use in cancer therapy. We observed that the doxorubicin loading increased with the number of double bonds on the polyphosphate block of non-cross-linked micelles. This diblock amphiphilic copolymer bearing pendant unsaturations appears thus particularly promising candidate to build micellar drug delivery systems for intravenous injection. [less ▲]

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See detailHot Melt Extrusion as a New Method to Form Inclusion Complexes with Cyclodextrins
Thiry, Justine ULg; Krier, Fabrice; Ratwatte, Shenelka et al

Conference (2016, April 06)

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See detailInvestigation of a suitable in vitro dissolution test for itraconazole-based solid dispersions
Thiry, Justine ULg; Broze, Guy ULg; Pestieau, Aude ULg et al

in European Journal of Pharmaceutical Sciences (2016)

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See detailCore cross-linked micelles of polyphosphoester containing amphiphilic block copolymers as drug nanocarriers
Ergül, Zeynep ULg; Vanslambrouck, Stéphanie; Cajot, Sébastien et al

in RSC Advances (2016), 6(48), 42081-42088

Poly(ethylene oxide)-b-polyphosphoester amphiphilic block copolymers are known to self-assemble into polymer micelles when dissolved into water. This work aims at reporting on the improvement of the ... [more ▼]

Poly(ethylene oxide)-b-polyphosphoester amphiphilic block copolymers are known to self-assemble into polymer micelles when dissolved into water. This work aims at reporting on the improvement of the stability of the micelles at high dilution by crosslinking the hydrophobic polyphosphoester micellar core. Typically, an unsaturated alkene side-chain was introduced on the cyclic phosphate monomer according to a one-step reaction followed by its organocatalyzed polymerization initiated by a poly(ethylene oxide) macroinitiator. This strategy avoids the use of any organometallic compounds in order to facilitate the purification and meet the stringent requirements of biomedical applications. After self-assembly into water, the micelles were cross-linked by simple UV irradiation. These cross-linked micelles have then been loaded by doxorubicin to evaluate their potential as drug nanocarriers and monitor the impact of crosslinking on the release profile. [less ▲]

Detailed reference viewed: 42 (16 ULg)