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See detailMesoporous silica impregnation using supercritical carbon dioxide: is the solubility in the supercritical fluid a critical parameter?
Koch, Nathan ULiege; Jennotte, Olivier ULiege; Rocks, Natacha ULiege et al

Conference (2019, May 20)

Recently, mesoporous silica (MS) has been used as a material able to maintain amorphous state of active pharmaceutical ingredients (APIs) due to appropriate pore size and pore morphologies. Among the ... [more ▼]

Recently, mesoporous silica (MS) has been used as a material able to maintain amorphous state of active pharmaceutical ingredients (APIs) due to appropriate pore size and pore morphologies. Among the impregnation methods of MS, techniques using supercritical carbon dioxide (sc-CO2) are promising tools since they provide many advantages, such as the ability to produce a final medicine without any residual toxic material. Solubility of the API in sc-CO2 is reported as one of the most critical parameters, which usually limits its use in drug formulation. Most of APIs have a poor solubility in sc-CO2 and the use of organic solvents is often required1,2. The goal of this study is to evaluate the feasibility of using sc-CO2 techniques for the impregnation of MS by APIs insoluble in sc-CO2. To do so, fenofibrate (FF) is used as model drug since by changing pressure and temperature conditions of the equipment, FF can be either soluble in sc-CO2 or not soluble but molten in the supercritical phase3. FF-MS complexes were produced by four different methods. Physical mixture (PM) composed of FF (70%, 50%, 43% and 41%) and MS were produced using a mixer during 15 minutes. Fusion at atmospheric pressure inclusion was performed in a water bath by keeping PM at a temperature above the fenofibrate melting point during 1h. Supercritical method with dissolved FF was performed by placing PM in a high pressure reactor for 1 hour under supercritical conditions (40°C and minimum 140 bars) leading to the dissolution of FF in sc-CO2 while supercritical method with melted FF was perfomed under supercritical conditions (60°C and 90 bars) leading to the melting but not to the dissolution of FF in sc-CO2. FF-MS complexes were characterized in terms of drug loading by high performance liquid chromatography, in terms of crystallinity by differential scanning calorimetry and in terms of dissolution profile by an appropriate in vitro dissolution test. We have shown that the use of sc-CO2 as fusion medium allows to work with lower temperature and an increased drug loading and homogeneity in comparison with classical melting inclusion methods. FF-MS formulations produced with sc-CO2 as fusion medium give similar crystallinity and dissolution results compare to those produced with supercritical fluids as solvent. Through this study, we show new possibilities of using sc-CO2 for APIs insoluble in this fluid. [less ▲]

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See detailDevelopment of new manufacturing processes for amorphous solid dispersions
Jennotte, Olivier ULiege; Koch, Nathan ULiege; Rocks, Natacha ULiege et al

Conference (2019, May 20)

Use of the hot-melt extrusion form amorphous solid dispersions of atorvastatin calcium trihydrate with a selection of three polymers in order to enhance its aqueous solubility

Detailed reference viewed: 22 (4 ULiège)
See detailHot melt extrusion as a solvent-free technique for the formation of a polymeric amorphous solid dispersion of atorvastatin
Jennotte, Olivier ULiege; Koch, Nathan ULiege; Collard, Laurence ULiege et al

Poster (2019, March 26)

Hot-melt extrusion as a solvent-free technique for the enhancement of BCSII molecules.

Detailed reference viewed: 20 (4 ULiège)
See detailHot melt extrusion as a solvent-free technique for the formation of a polymeric amorphous solid dispersion of atorvastatin
Jennotte, Olivier ULiege; Koch, Nathan ULiege; Collard, Laurence ULiege et al

Scientific conference (2018, December 19)

Water-solubility enhancement of atorvastatin using the hot melt extrusion for the production of a polymeric amorphous solid dispersion

Detailed reference viewed: 42 (16 ULiège)