References of "Evrard, Brigitte"
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See detailChallenges of fused deposition modeling 3D printing in pharmaceutical applications: Where are we now?
Parulski, Chloé ULiege; Jennotte, Olivier ULiege; Lechanteur, Anna ULiege et al

in Advanced Drug Delivery Reviews (2021), 175

In recent years, fused deposition modeling has become one of the most used threedimensional printing technologies in the pharmaceutical field. The production of personalized dosage forms for ... [more ▼]

In recent years, fused deposition modeling has become one of the most used threedimensional printing technologies in the pharmaceutical field. The production of personalized dosage forms for individualized therapy and the modification of the drug release profile by the elaboration of complex geometries make fused deposition modeling a promising tool for small-scale production. However, fused deposition modeling has a considerable number of challenges to overcome. They are divided into three categories of parameters. Materialspecific parameters encompass the physicochemical properties of the filament, like thermal, mechanical and rheological properties. They determine the feasibility of the printing process. Operation-specific parameters relate to the processing conditions of printing, such as printing temperature and infill density, which have an influence on the final quality and on the dissolution behavior of the objects. The printer equipment is defined by the machine-specific parameters. Some modifications of this equipment also enhance the performance of the printing process. The aim of this review is to highlight the major fused deposition modeling critical process parameters in the pharmaceutical field and possible solutions in order to speed up the development of objects in the pharmaceutical market. [less ▲]

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See detailInnovative lipoplexes formulations with enhanced siRNA efficacy for cancer treatment: Where are we now?
Berger, Manon ULiege; Lechanteur, Anna ULiege; Evrard, Brigitte ULiege et al

in International Journal of Pharmaceutics (2021)

Over the past two decades, RNA interference has become an extensively studied mechanism to silence gene and treat diseases including cancer. siRNA appears as a promising strategy that could avoid some ... [more ▼]

Over the past two decades, RNA interference has become an extensively studied mechanism to silence gene and treat diseases including cancer. siRNA appears as a promising strategy that could avoid some side effects related to traditional chemotherapy. Considering the weak stability of naked siRNA in blood, vectors like cationic liposomes or Lipid Nanoparticles (LNPs) are widely used to carry and protect siRNA until it reaches the tumor targeted. Despite extensive research, only three RNAi drugs are currently approved by the Food and Drug Administration, including only one LNP formulation of siRNA to treat hereditary ATTR amyloidosis. This shows the difficulty of lipoplexes clinical translation, in particular in cancer therapy. To overcome the lipoplexes limitations, searches are made on innovative lipoplexes formulations with enhanced siRNA efficacy. The present review is focusing on the recent use of pH-sensitive lipids, peptides and cell-penetrating peptides or polymers. The incorporation of some of these components in the lipoplex formulation induces a fusogenic property or an enhanced endosomal escape, an enhanced cellular uptake, an enhanced tumor targeting, an improved stability in the blood stream …These innovations appear critical to obtain an efficient siRNA accumulation in tumor cells with effective antitumor effect considering the complex tumor environment. [less ▲]

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See detailHow do infill density and polymer composition of tablets produced by hotmelt extrusion coupled with Fused Deposition Modeling 3D printing influence the dissolution profile of a BCS II molecule ?
Parulski, Chloé ULiege; Gresse, Eva ULiege; Jennotte, Olivier ULiege et al

Conference (2021, April 06)

Introduction: During last years, the use of three-dimensional (3D) printing for drug manufacturing has considerably increased in the field of pharmaceutical research. The development of complex geometries ... [more ▼]

Introduction: During last years, the use of three-dimensional (3D) printing for drug manufacturing has considerably increased in the field of pharmaceutical research. The development of complex geometries leading to different drug release profiles is an application that make 3D printing and, more specifically, Fused Deposition Modeling (FDM) a promising tool. In fact, many active pharmaceutical ingredients are classified in the Biopharmaceutics Classification System class II (BCS II) since they are poorly soluble. Thus, the goal of this work is to enhance the solubility and the bioavaibilty of poorly soluble drugs by the use of hot-melt extrusion (HME) coupled with FDM to form of an amorphous solid dispersion. Method: The selected model drug was Itraconazole (ITZ), a BCS II active molecule. Hot-melt extrusion process was performed on three formulations containing 25% of ITZ and different proportions of Affinisol® 15LV (hydroxypropylmethylcellulose) and Kollidon® VA 64 (vinylpyrrolidone-vinyl acetate copolymer). For each formulation, tablets with infill densities of 20%, 50% and 80% were printed (Figure 1). Results: Differential scanning calorimetry (DSC) analysis shows that the three formulations contain ITZ in its amorphous form. The results of dissolution tests in 0.1 M HCl indicate that the dissolution profile of the drug is influenced by the polymer composition and the infill density of the tablets. Conclusions: In conclusion, for the three formulations, the lower the tablet infill is, the higher the porosity and the faster the dissolution rate are. A solubility profile similar to that of Sporanox® (the correspondent commercialized drug in Belgium) is even obtained with one of the tablet formulations with an infill density of 20%, which is highly encouraging for future experiments. [less ▲]

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See detailAmphiphilic N-vinyl pyrrolidone-based polymers as PEG alternatives to avoid blood proteins adsorption around liposomes
Berger, Manon ULiege; Toussaint, François ULiege; Pairoux, Charlotte ULiege et al

Conference (2021, April 06)

Introduction: After a systemic administration, liposomes are quickly covered by proteins leading to the formation of a protein corona. This corona is responsible for a change of physicochemical properties ... [more ▼]

Introduction: After a systemic administration, liposomes are quickly covered by proteins leading to the formation of a protein corona. This corona is responsible for a change of physicochemical properties (as an increase of the size), pharmacokinetics, biodistribution, targeting ability, … [1]. Polyethylene glycol (PEG) is generally grafted onto the liposomes surface to reduce these non-specific interactions with blood components [2]. Since PEG faces some issues [3], alternatives are searched which should optimally prevent the formation of this corona. The goal of this study is to evaluate the protein corona formation around cationic liposomes (DOTAP/Chol/DOPE 1/0.75/0.5 molar ratio) encapsulating a model siRNA. Method: Different formulations were tested: naked liposomes, PEGylated liposomes (15% molar ratio of total lipids) and liposomes grafted with the new synthetic amphiphilic N-vinyl pyrrolidone-based polymers. Liposomes were incubated in FBS for two hours and their sizes were compared before and after incubation. Measurements were performed by DLS and NTA. An increase in liposomes size is related to the adsorption of proteins around the particles. Results: Results show that 15% PEG allows to prevent a significant size increase. However, 15% amphiphilic N-vinyl pyrrolidone-based polymers are not able to prevent corona formation since both analyses revealed a huge increase of particles sizes. A higher concentration (40%) was necessary to hinder a significant size increase meaning probably that their insertion/coating into/onto lipoplexes is different compared to PEG. Conclusions: To conclude, we showed that new synthetic amphiphilic N-vinyl pyrrolidone-based polymers were able to prevent protein corona formation around lipoplexes. Further studies are ongoing in order to evaluate the transfection capacity of these coated-vectors carrying siRNA. [less ▲]

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See detailImpact of amphiphilic copolymer used as PEG alternative on the formation of a protein corona around coated-liposomes encapsulating siRNA
Berger, Manon ULiege; Toussaint, François ULiege; Pairoux, Charlotte ULiege et al

Conference (2021, March 04)

After a systemic administration, liposomes are quickly covered by blood proteins leading to the formation of a protein corona. This corona is responsible for liposomes with a change of physicochemical ... [more ▼]

After a systemic administration, liposomes are quickly covered by blood proteins leading to the formation of a protein corona. This corona is responsible for liposomes with a change of physicochemical properties (as an increase of the size), pharmacokinetics, biodistribution, targeting ability and cellular uptake, complement activation and liposomes rapid clearance. To decrease this phenomenon, polyethylene glycol (PEG) is generally grafted onto liposomes surface to reduce non-specific interactions with blood components. Since PEG faces some issues, alternatives are searched which should optimally protect the liposomes surface from proteins adsorption. The goal of this study was to evaluate the protein corona formation around cationic liposomes (DOTAP/Chol/DOPE 1/0.75/0.5 molar ratio) encapsulating siRNA (N/P ratio of 2.5). Different formulations were tested: naked liposomes, PEGylated liposomes (15% molar ratio of total lipids) and liposomes grafted with new synthetic amphiphilic N-vinyl pyrrolidone-based copolymers used as PEG alternatives (B15b and B19a differing by the number of monomer units). Liposomes were incubated in Fetal Bovine Serum for two hours and their sizes were compared before and after incubation. An increase in liposomes size was related to the adsorption of proteins around the particles. Measurements were performed with Malvern Zetasizer® and Malvern NanoSight®. Results showed that PEG was already effective at 15% to prevent a significant increase of the size. However, both alternatives used at this concentration were not able to prevent corona formation since both analyses revealed a huge increasing of particles sizes. Higher concentration (40%) was necessary to hinder a significant increase of the size meaning probably that their insertion/coating into lipoplexes are different compared to PEG. These polymers may therefore be a great alternative able to face PEG limitations. To conclude, through this project, we have proven that our new amphiphilic copolymers were able to prevent protein corona formation around lipoplexes. Further studies are ongoing in order to evaluate the transfection capacity of these coated-vectors carrying siRNA. [less ▲]

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See detailInvestigation of the impact of polymer composition and infill density of solid oral forms produced by hot-melt extrusion coupled with 3D printing on the dissolution rate of itraconazole
Parulski, Chloé ULiege; Gresse, Eva ULiege; Jennotte, Olivier ULiege et al

Conference (2021, March 04)

In recent years, scientific interest in using three-dimensional (3D) printing for drug manufacturing has considerably increased. Modification of drug release profiles by the elaboration of complex ... [more ▼]

In recent years, scientific interest in using three-dimensional (3D) printing for drug manufacturing has considerably increased. Modification of drug release profiles by the elaboration of complex geometries is an application that make 3D printing and, more precisely, Fused Deposition Modeling (FDM) a promising tool for the pharmaceutical field. In fact, nowadays, many active pharmaceutical ingredients are classified in the Biopharmaceutics Classification System class II (BCS II) since they are poorly soluble. Therefore, the aim of this work is to improve the solubility, thus, the bioavaibilty of poorly soluble drugs by the formation of an amorphous solid dispersion by the use of hot-melt extrusion (HME) coupled with FDM 3D printing. Itraconazole (ITZ), a BCS II active molecule, was selected as the model drug. Three formulations containing different proportions of Affinisol® 15LV (hydroxypropylmethylcellulose) and Kollidon® VA 64 (vinylpyrrolidone-vinyl acetate copolymer) and a constant proportion of 25% of ITZ were hot-melt extruded. For each formulation, tablets with infill densities of 20%, 50% and 80% and constant weight were successfully printed (Figure 1). The results obtained with the differential scanning calorimetry (DSC) analysis show that ITZ is in an amorphous form in all the three formulations. The results of dissolution tests in 0.1 M HCl indicate that the polymer composition of the tablets has an influence on the dissolution profile of the drug. Moreover, the dissolution rate of the tablets is also influenced by their infill density. To conclude, we have found that, for the three formulations, the lower the tablet infill is, the higher the porosity and the faster the dissolution rate are. One of the tablet formulations with an infill density of 20% even have a solubility profile similar to that of Sporanox® (the correspondent commercialized drug in Belgium) which is highly encouraging for future experiments. [less ▲]

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See detailAntimicrobial potentials of essential oils extracted from West African aromatic plants on common skin infections
Sounouvou, Axel Gérald Hope Tognidé ULiege; Toukourou, Habib; Catteau, Lucy et al

in Scientific African (2021), 11

During the last decade, the advent of multi-drug resistant pathogens responsible for skin infections tends to make conventional treatments obsolete. Even though many studies have reported the ... [more ▼]

During the last decade, the advent of multi-drug resistant pathogens responsible for skin infections tends to make conventional treatments obsolete. Even though many studies have reported the antimicrobial properties of essential oils (EOs), the inconsistent use of various susceptibility testing methods has made information on antimicrobial potential of many EO varieties fragmentary. Using a single method approach, the objective of this work was to assess and to compare the antibacterial and antifungal properties, against skin pathogens, of EOs extracted from West African aromatic plants. Twenty-three plant samples collected in Benin and Burkina Faso were screened against 20 bacterial and fungal isolates obtained from skin lesions. Activity was evaluated by the determination of minimal inhibitory concentrations (MICs), with readings facilitated by the use of resazurin, a blue dye metabolized into pink resorufin by viable cells. Following this screening, nine EOs were found particularly active with MICs lower than 0.35% v/v. Gas Chromatography-Mass Spectrometry (GC/MS) analysis was used to deter- mine the phytochemical profile of these active EOs which were found exceptionally rich in oxygenated monoterpenes, especially aldehydes, alcohols or phenols and their derivatives. Through this study, we demonstrated that several West African EOs have a significant an- timicrobial potential which could, however, be considerably impacted by plant growing or harvesting place due to phytochemical composition variation. These EOs, even if their antimicrobial effects appeared lower than those of conventional antibiotics, constitute easily available mixtures of active compounds and could nevertheless be considered, in the context of increasing multidrug resistance, as complementary or alternative therapies in common skin infections management. [less ▲]

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See detailDevelopment of a highly persistent silicone-based sprayable emulsion containing essential oils for treatment of skin infections
Sounouvou, Axel Gérald Hope Tognidé ULiege; Defourny, Charline ULiege; Gbaguidi, Fernand et al

in International Journal of Pharmaceutics (2021), 596

Essential oils have known a renewed interest, particularly for their antimicrobial properties. In the field of skin delivery of essential oils, fluid oil-in-water (O/W) emulsions have been studied for ... [more ▼]

Essential oils have known a renewed interest, particularly for their antimicrobial properties. In the field of skin delivery of essential oils, fluid oil-in-water (O/W) emulsions have been studied for several years in order to improve their stability. When dealing with infections of the upper skin layers, these vehicles, in spite of their low viscosity, must have a good skin persistence and also concentrate the essential oil components in the target skin layers. Given the well-known ability of alkylsiloxysilicate resins to induce a very substantive and non-occlusive film after cutaneous application in an appropriate preparation, it has been undertaken to use them to prepare a highly persistent O/W fluid emulsion of essential oil. Hence, after the successful development of a fluid silicone-in-water (Si/W) emulsion integrating a 100% trimethylsiloxysilicate resin, the essential oil was incorporated in this emulsion. The physical and chemical stabilities of the prepared emulsion were then studied in the final packaging under different storage conditions. In addition, the skin penetration profile of essential oil from this vehicle was investigated, ex vivo, on pig ear skin, using Franz diffusion cells and analytical techniques such as confocal Raman microscopy. As the developed vehicle was found to meet our delivery expectations, its skin tolerance has been proven by an in vivo chromametric evaluation of its irritant potential. The skin persistence of this emulsion containing an antimicrobial essential oil was then studied. Considering its properties, the developed emulsion is expected to represent a real asset in the treatment of skin infections, particularly infections of upper layers of human skin such as dermatophytosis. [less ▲]

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See detailSterilization methods of liposomes: drawbacks of conventional methods and perspectives
Delma, Kouka Luc ULiege; Lechanteur, Anna ULiege; Semde, Rasmané et al

in International Journal of Pharmaceutics (2021)

Liposomes are targeted drug delivery systems that are of great pharmaceutical and therapeutic interest. Parenteral route is the main way used for liposome administration. In this case, their sterility is ... [more ▼]

Liposomes are targeted drug delivery systems that are of great pharmaceutical and therapeutic interest. Parenteral route is the main way used for liposome administration. In this case, their sterility is a requirement. However, due to the particular sensitivity of liposomes and their tendency to physicochemical alterations, their sterilization remains a real challenge. Conventional sterilization methods such as heat, ethylene oxide, ultraviolet and gamma irradiations are considered as unsuitable for liposome sterilization and the recommended methods for obtaining sterility of liposomes are filtration and aseptic manufacturing. Unfortunately, these recommended methods are not without limitations. This review outlines the difficulties associated with the use of these different classical methods for obtaining liposome sterility. The effects on liposome physicochemical and biopharmaceutical characteristics as well as efficacy, toxicity and practical problems of these sterilization techniques have been discussed. The search for an alternative method being therefore necessary, the applicability of supercritical carbon dioxide (ScCO2) technology, which is nowadays a promising strategy for the sterilization of sensitive products such as liposomes, is also examined. It appears from this analysis that ScCO2 could effectively be an interesting alternative to achieve sterility of liposomes, but for this, sterilization assays including challenge tests and optimization studies are needed. [less ▲]

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See detailSystematic study of liposomes composition towards efficient delivery of plasmid DNA as potential application of dermal fibroblasts targeting
Bellefroid, Coralie ULiege; Reusch, Céline ULiege; Lechanteur, Anna ULiege et al

in International Journal of Pharmaceutics (2021), 592

The use of non-viral DNA vectors to topically treat skin diseases has demonstrated a high potential. However, vectors applied on the skin face extracellular barriers including the stratum corneum and ... [more ▼]

The use of non-viral DNA vectors to topically treat skin diseases has demonstrated a high potential. However, vectors applied on the skin face extracellular barriers including the stratum corneum and intracellular barriers such as the endosomal escape and the nuclear targeting of the plasmid DNA. The aim of this study was to develop a formulation suitable for dermal application and effective for delivering plasmid DNA into cells. Different formulations were prepared using different cationic lipids (DOTAP, DC-Chol, DOTMA) and co-lipids (DOPE, DSPE). Lipoplexes were produced by complexing liposomes with plasmid DNA at different pDNA/CL (w/w) ratios. Our results showed that appropriate pDNA/CL ratios allowing total complexation of plasmid DNA differed depending on the structure of the lipid used. The transfection rates showed that (i) higher rates were obtained with DOTMA lipoplexes, (ii) DC-Chol lipoplexes provided a transfection twice as important as DOTAP lipoplexes and (iii) when DSPE was added, the cytotoxicity decreased while transfection rates were similar. We found that formulations composed of DC-Chol:DOPE:DSPE or DOTMA:DOPE were appropriate to complex plasmid DNA and to transfect human primary dermal fibroblasts with efficacy and limited cytotoxicity. Therefore, these formulations are highly promising in the context of gene therapy to treat skin diseases. [less ▲]

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See detailA supercritical fluid technology for liposome production and comparison with the film hydration method
Penoy, Noémie ULiege; Grignard, Bruno ULiege; Evrard, Brigitte ULiege et al

in International Journal of Pharmaceutics (2021), 592

Liposomes were produced by an innovative method using supercritical carbon dioxide as a dispersing agent. A quality by design strategy was used to find optimal production conditions with specific ... [more ▼]

Liposomes were produced by an innovative method using supercritical carbon dioxide as a dispersing agent. A quality by design strategy was used to find optimal production conditions with specific parameters (lipid concentration, dispersion volume, agitation rate, temperature and pressure) allowing the production of liposomes with predicted physicochemical characteristics (particles size and PdI). Two conditions were determined with specific production parameters. It was shown that these two conditions allowed the production of liposomes of different compositions and that most of the liposome formulations had size and dispersity in accordance with the prediction values. The condition involving the higher lipid concentration showed a higher variability in terms of size and dispersity. However, this variability remained acceptable. This innovative supercritical method allowed the production of liposomes with physicochemical characteristics similar to those obtained by the conventional thin film hydration method. This new supercritical carbon dioxide method easily scalable in GMP conditions is a one-step production method contrarily to conventional methods which generally need an additional step as extrusion to homogenize the size of liposomes. [less ▲]

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See detailStérilisation des liposomes par le dioxyde de carbone en phase supercritique : effets des conditions sur leurs caractéristiques physicochimiques
Delma, Kouka Luc ULiege; Evrard, Brigitte ULiege; Piel, Géraldine ULiege et al

Conference (2020, December)

Introduction : Les liposomes sont des vecteurs de médicaments généralement administrés par voie parentérale. Cependant, les techniques actuellement utilisées pour obtenir leur stérilité présentent des ... [more ▼]

Introduction : Les liposomes sont des vecteurs de médicaments généralement administrés par voie parentérale. Cependant, les techniques actuellement utilisées pour obtenir leur stérilité présentent des limites. Le dioxyde de carbone supercritique (CO2Sc) représente une stratégie prometteuse pour la stérilisation des produits sensibles comme les liposomes. Le but de ce travail est d’étudier l’applicabilité de la technologie du CO2Sc à la stérilisation des liposomes. Méthodologie : Les liposomes ont été préparés par la méthode d’hydratation du film lipidique puis leurs caractéristiques physico-chimiques ont été déterminées avant et après soumission à 4 conditions de stérilisation par le CO2Sc choisies : C1 (70°C, 150 bar, 240 min), C2 (38° C, 85 bar, 45 min, 0.25 % H2O /0.15 % H2O2) / 0.5% anhydride acétique), C3 (35° C, 104 bar, 180 min, 0.08 % acide peracétique ) et C4 (40° C, 270 bar, 90 min, 200 ppm H2O2). Résultats et discussion : Des modifications de caractéristiques physicochimiques ont été observés après soumission des liposomes aux conditions C1, C2 et C3. Par contre, aucune variation majeure de caractéristiques n’a été mise en évidence après traitement des liposomes par la condition C4. L’absence de variation avec la condition C4 pourrait s'expliquer par les paramètres (température, pression, temps de traitement) assez souples de cette condition, la faible quantité et la décomposition rapide de l’additif utilisée. Conclusion : La condition C4 semble être la meilleure en termes de maintien des caractéristiques physicochimiques des liposomes et pourrait donc constituer une condition de stérilisation des liposomes par le CO2Sc. [less ▲]

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See detailPhysical formulation approaches for improving aqueous solubility and bioavailability of ellagic acid: A review
Nyamba, Isaïe ULiege; Lechanteur, Anna ULiege; Semdé, Rasmé et al

in European Journal of Pharmaceutics and Biopharmaceutics (2020)

Ellagic acid (EA) is a polyphenolic active compound with antimalarial and other promising therapeutic activities. However, its solubility and its permeability are both low (BCS IV). These properties ... [more ▼]

Ellagic acid (EA) is a polyphenolic active compound with antimalarial and other promising therapeutic activities. However, its solubility and its permeability are both low (BCS IV). These properties greatly compromise its oral bioavailability and clinical utilizations. To overcome these limitations of the physicochemical parameters, several formulation approaches, including particle size reduction, amorphization and lipid-based formulations, have been used. Although these strategies have not yet led to a clinical application, some of them have resulted in significant improvements in the solubility and bioavailability of EA. This critical review reports and analyses the different formulation approaches used by scientists to improve both the biopharmaceutical properties and the clinical use of EA. [less ▲]

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See detailImpregnation of mesoporous silica with poor aqueous soluble molecule using pressurized carbon dioxide: is the solubility in the supercritical and subcritical phase a critical parameter?
Koch, Nathan ULiege; Jennotte, Olivier ULiege; Grignard, Bruno ULiege et al

in European Journal of Pharmaceutical Sciences (2020), 150

Recently, mesoporous silica (MS) has been used as a material able to maintain amorphous state of active compounds and therefore, enhance the oral bioavailability of BCSII drugs. Among impregnation methods ... [more ▼]

Recently, mesoporous silica (MS) has been used as a material able to maintain amorphous state of active compounds and therefore, enhance the oral bioavailability of BCSII drugs. Among impregnation methods of MS, techniques using supercritical carbon dioxide (sc-CO2) are promising tools. Solubility of compounds in sc-CO2 is reported as one of the most critical parameters, which usually limits its use in drug formulation. Indeed, most of compounds have poor solubility in sc-CO2. The aim of this work is to compare different MS and to study alternative processes using pressurized CO2 for insoluble molecule in sc-CO2. By using high pressure reactor, DSC, HPLC and in vitro dissolution tests, the crystallinity and dissolution profiles of MS with different pore size (6.6 nm, 25.0 nm and 2.5 nm) impregnated with fenofibrate (FF) under sc-CO2 were compared to select the most appropriate carrier. Then, the selected MS has been impregnated under supercritical, subcritical and atmospheric conditions. We have shown that the MS pore size of 6.6 nm provides the higher amorphous drug loading capacity as well as the faster and higher drug dissolution. In addition, FF-MS formulations produced with pressurized CO2 as fusion medium, both in subcritical and supercritical conditions; give similar crystallinity and dissolution results compared to those produced with supercritical fluids as solvent. Through this study, we show new possibilities of using CO2 for insoluble compounds in this fluid. [less ▲]

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